Amyotrophic lateral sclerosis patient antibodies label Ca2+ channel α1 subunit

Sporadic amyotrophic lateral sclerosis is an idiopathic human degenerative disease of spinal cord and brain motor neurons. Prior studies demonstrated that most patients with amyotrophic lateral sclerosis posses immunoglobulins that bind to purified L-type voltage-gated calcium channels, that titers of anti–voltage-gated calcium channel antibodies correlate with disease progression rates, and that amyotrophic lateral sclerosis patient-derived antibodies (ALS IgG) produce electrophysiological changes in the function of voltage-gated calcium channels. Using Western transfer immunoblots and enzyme-linked immunosorbent assays, the calcium ionophore–forming α₁ subunig of the voltage-gated calcium channel is now identified as the major voltage-gated calcium channel antigen to which ALS IgG binds. Additionally, the binding of an L-type voltage-gated calcium channel α₁ subunit–directed monoclonal antibody, which itself mimics the effects of ALS IgG on skeletal muscle voltage-gated calcium channel currents, is selectively prevented by preaddition of ALS IgG. Voltage-gated calcium channel–binding IgG from patients with Lambert-Eaton myasthenic syndrome appears to be differentiated from ALS IgG by the reactivity of the former to both α₁ and β subunits of the calcium channel. These assays provide further evidence linking amyotrophic lateral sclerosis to an autoimmune process, and suggest one means to differentiate immunoglobulins from patients with amyotrophic lateral sclerosis from those of patients with another autoimmune disease expressing calcium channel antibodies.     

Factors associated with hypertension in Nigerian civil servants

BACKGROUND. Study of hypertension in segments of West African populations in transition toward Westernization may lead to better understanding of the high risk for hypertension among Westernized blacks. METHODS. Five hundred fifty-nine urban civil servants, ages 25-54, were recruited from six ministries of Bendel State, Nigeria. Blood pressure, physical measurements, urinary protein and glucose, fasting blood glucose, and demographic data were collected at the workplace. Subjects were classified as senior staff (professionals or administrators) or junior staff (non-administrators). RESULTS. Among 172 male senior staff, the age-adjusted rate of hypertension (diastolic blood pressure > or = 90 mm Hg, systolic blood pressure > or = 140 mm Hg, or on an antihypertensive medication) was 43% and occurrence rose dramatically from 21 to 63% across age groups 25-34 to 45-54, respectively. Among 266 male junior staff, the age-adjusted rate of hypertension was 23%, and occurrence did not rise with age. Logistic regression showed that body mass index (kg/m2), age, alcohol drinking, and being senior staff were all independently related to hypertension in men. On the other hand, the age-adjusted rate of hypertension in 121 women was 20% and was significantly related only to body mass index. CONCLUSION. Male urban civil servants appeared to have a risk for hypertension similar to that of U.S. black males. Age, body mass index, alcohol drinking, and other unidentified factors related to higher socioeconomic status were strong determinants of hypertension in this population.     

SPROUT,HIPPO and CAESA: Tools for de novo structure generation and estimation of synthetic accessibility

Summary Several components of a system for structure generation are now well developed. HIPPO is a program that characterises a receptor binding site for potential target sites within the cavity that can be used in de novo design. The target sites include simple and complex hydrogen bonds, covalent bonds and bonds to metal ions. The SPROUT program for structure generation consists of two main components: the first is skeleton generation, followed by atom substitution to convert the solution skeletons to molecules. A new method of skeleton generation is presented here, where part skeletons are grown outwards from each target site. The part skeletons are then connected together to form solution skeletons. Finally the CAESA program is described, that ranks the output from SPROUT according to ease of synthesis.     

MESENTERIC CYST

Mesenteric cyst is one of the rarest abdominal tumours, with approximately 820 cases reported since 1507. The incidence varies from 1 per 100000 to 250000 admissions. The lack of characteristic clinical features and radiological signs may present great diagnostic difficulties. The cyst may present in one of three ways: (i) non-specific abdominal features; (ii) an incidental finding; or (iii) an acute abdomen. Abdominal pain is the major presenting symptom. Abdominal mass is found in more than 50% of cases and 40% of cases are discovered incidentally. More than one aetiological mechanism is probably involved in the development of mesenteric cysts. Mesenteric cysts have been reported from the duodenum to the rectal mesentery but are most commonly located in the ileal mesentery. Malignant cysts occur in less than 3% of cases. Enucleation of the cyst is the treatment of choice. Knowledge of these tumours is important due to the various complications associated with suboptimal surgical management. Two cases of mesenteric cysts are presented including a recurrent mesenteric cyst in a post-partum woman demonstrating the inferior technique of internal marsupialization. The association of mesenteric cyst with pregnancy is discussed.     

Is the apparent U-shape of well-being over the life course a result of inappropriate use of control variables? A commentary on Blanchflower and Oswald (66: 8, 2008, 1733–1749)

In their article in this journal “Is well-being U-shaped over the life cycle?” Blanchflower and Oswald (Blanchflower, D.G., & Oswald, A.J. (2008). Is well-being U-shaped over the life cycle? Social Science & Medicine, 66, 1733–1749) report the results of an ambitious cross-national study of age and well-being and conclude that in most societies studied the well-being of adults tends to be high in young adulthood and old age and lowest around age 40. I argue that the appearance of this U-shaped curve of well-being is the result of the use of inappropriate and questionable control variables. The most clearly inappropriate control variable is marital status, the control of which to a large extent accounts for the U-shaped curve. Most researchers who have studied the relationship between being married and being happy believe that happiness affects marital status (happier people are more likely to marry and stay married), and of course a variable that is affected by the dependent variable should not be included as a control variable in a simple recursive model. Such control variables as income and education are suspect because the relationship between them and well-being is likely to be partially spurious, and such variables as race and whether or not persons lived with both parents at age 16 should not be controlled, because they cannot affect or be affected by age. Finally, year of survey should not be controlled because of the age-period-cohort conundrum, which makes including age, period, and cohort all as predictor variables in a regression inappropriate (and impossible if the three variables are measured precisely and comparably). The only clearly appropriate control variable is birth cohort, and when only it is controlled, the regression data become estimates of how the well-being of persons has actually changed as they have gone through the life course. I argue that such estimates are much more useful than the counterfactual abstractions provided by Blanchflower and Oswald (Blanchflower, D.G., & Oswald, A.J. (2008). Is well-being U-shaped over the life cycle? Social Science & Medicine, 66, 1733–1749), and I conclude that those authors (or someone else) could make a very important contribution by redoing their analyses with birth cohort as the only control variable. I do that with the American happiness data and find that the results do not come close to the U-shaped pattern.     

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.     

Effect of Mutans streptococcal colonization on plaque formation and regrowth in young children--a brief commnunication.

OBJECTIVES: Visible plaque on the maxillary anterior teeth of young children has been identified as a risk indicator for early childhood caries. The present study examined whether this plaque is related to the colonization of children's teeth with Mutans streptococci (MS) or toothbrushing frequency. METHODS: Thirty-nine children, aged 12 to 36 months, had plaque scores, and plaque samples were taken from the labial surfaces of the maxillary incisors at baseline and repeated 3 days after suspended oral hygiene (plaque regrowth). RESULTS: A positive correlation was found between the baseline percent MS and regrowth plaque score and between baseline and regrowth plaque scores. Plaque scores of those that brushed zero to one time a day were not different from those who brushed two or more times a day. CONCLUSIONS: This study suggests that the presence of plaque on the anterior teeth of young children is consistent and related to MS colonization.     

Use of split-liver allografts does not impair pediatric recipient growth.

The use of split-liver (SL) allografts continues to be an excellent option for many pediatric recipients. Patient and graft survival with this graft type are comparable to patient and graft survival with whole organ grafts. Quality-of-life issues, specifically growth, for SL recipients have not been compared to those of recipients of more conventional whole-organ recipients. Pediatric recipients of SL and whole allografts at 2 institutions were identified. Height, z score, and delta z score were calculated for all recipients for each year after transplant. Between 1995 and 2004, 201 pediatric liver transplants were analyzed. Data were collected on 39 split-graft recipients and 36 whole-size recipients. Only subjects 3 years or younger were included in the study. Growth retardation was present in all recipients at transplant. Height z score post split and whole-size transplant were not statistically different at 1- (P = 0.65), 2- (P = 0.13), and 3-year (P = 0.32) anniversaries, respectively. Catch-up growth was present only in recipients of split grafts. In conclusion, the use of split grafts as opposed to whole-size grafts revealed no significant differences in terms of linear growth. Our report indicates that split-liver transplantation does not impair recipient growth.