Systemic lupus erythematosus in a multiethnic US cohort: XXXIV. Deficient mannose-binding lectin exon 1 polymorphisms are associated with cerebrovascular but not with other arterial thrombotic events

OBJECTIVE: To study the association between deficient mannose-binding lectin (MBL) genotypes and arterial thrombotic events in systemic lupus erythematosus (SLE). METHODS: Patients with SLE of Hispanic, African American, and Caucasian ethnicity from LUMINA (LUpus in MInorities, NAture versus nurture), a multiethnic, longitudinal study of outcome, were studied. Arterial thrombotic events (myocardial infarction, angina, coronary artery bypass graft surgery, stroke, claudication, gangrene, or tissue loss and/or peripheral arterial thrombosis) that occurred after diagnosis were recorded. Genotyping for MBL gene polymorphisms was performed and their distribution was compared between patients who did and did not have thrombotic events. RESULTS: There were 58 events (21 cardiovascular, 27 cerebrovascular, and 10 peripheral vascular) in 48 patients. Patients who had thrombotic events were older and were more likely to be smokers, to have more severe disease, and to have accrued more damage overall. Also, a larger proportion of these patients had C-reactive protein values in the highest quintile of distribution. No significant difference in arterial thrombotic events was found in patients homozygous for MBL-deficient alleles compared with others. Similar results were seen within ethnic groups. Caucasians who developed potential thrombotic events exhibited a higher frequency of MBL-deficient alleles, but the difference was not statistically significant for all events together or for cardiovascular and cerebrovascular events combined. However, when only the cerebrovascular events were considered, the difference became statistically significant. CONCLUSION: Age, smoking, and measures of activity and damage were associated with arterial thrombotic events in patients with SLE, but MBL-deficient genotypes were not, with cerebrovascular events in Caucasians being the exception. The relationship between MBL-variant alleles and arterial thrombotic events may exist only within select ethnic groups and event types.     

Pulmonary involvement in systemic sclerosis: associations with genetic, serologic, sociodemographic, and behavioral factors

OBJECTIVE: To determine the relative contributions of genetic, clinical, serologic, sociodemographic, and behavioral/psychological variables to early pulmonary involvement in the Genetics versus Environment in Scleroderma Outcome Study cohort. METHODS: At the baseline visit (V0), 203 patients with systemic sclerosis (SSc) were examined (104 whites, 39 African Americans, and 60 Hispanics). We obtained sociodemographic, behavioral/psychological (illness behavior, social support, learned helplessness, smoking, drinking), clinical, serologic (autoantibodies), and genetic (HLA class II and FBN1 genotypes) factors; pulmonary function test results; electrocardiograms; and chest radiographs. Data analysis included Fisher's exact test, chi-square test, Student's t-test, analysis of variance, and stepwise linear and logistic regression methods. RESULTS: Significant pulmonary involvement was seen in 25% of patients within 2.8 years of SSc diagnosis. At V0, pulmonary fibrosis was significantly higher in African Americans compared with whites or Hispanics. African Americans had significantly lower percent predicted forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV(1)) compared with whites and significantly lower percent predicted diffusing capacity for carbon monoxide (DLCO) compared with whites and Hispanics. Significant, independent associations impacting early pulmonary involvement included African American ethnicity, skin score, serum creatinine and creatine phosphokinase values, hypothyroidism, and cardiac involvement. Anticentromere antibody seropositivity was a significant, independent, protective factor for restrictive lung disease and FVC or DLCO values. African Americans had significantly increased frequencies of anti-topoisomerase I, fibrillarin, and RNP autoantibodies compared with whites. African Americans scored significantly lower on the Interpersonal Support Evaluation List and significantly higher on the Illness Behavior Questionnaire. CONCLUSION: Early pulmonary involvement in SSc appears to be influenced by several factors delineated by ethnicity, including racial, socioeconomic, behavioral, and serologic determinants.     

Double Nephrotomography*

With meticulous attention to classical nephro-tomographic technique the double nephrotomogram should increase the accuracy of the diagnosis of renal masses and diminish the number of indeterminate cases diagnosed during routine nephrotomography. Solid tumours will appear as dense or denser than the normal renal parenchyma in the initial nephrotomogram and may appear lucent in the delayed study. In necrotic tumours, the thickened wall of the tumour will be more apparent in the vascular phase while the mass is frequently radiolucent in the tubular phase. The change in density of a lesion or of the wall of a lesion is strongly suggestive of carcinoma. Renal cysts persistently exhibit homogeneous radiolucency in both series.     

Pyelovenous backflow: Facts, fallacies and significance

Pyelovenous backflow is discussed in the light of current theories. In acutely obstructed but otherwise normal kidneys, this type of backflow does not occur during routine excretory urography. Pyelovenous backflow may, however, be associated with carcinoma, hydronephrosis, hamartomas, and arteriovenous malformation.     

Antennal sensilla of the New World screwworm fly, Cochliomyia hominivorax (Diptera: Calliphoridae)

Antennal sensilla of the Cochliomyia hominivorax were studied by scanning electron microscopy. Thirteen subtypes of sensilla were identified in the fly antenna. In the antennal funiculus, nine subtypes were found: one trichoid, three basiconic, and five coeloconic. Among these, olfactory sensilla were morphologically recognized. Long bristle sensilla presenting various sizes and distribution patterns were observed in the scape and pedicel. In this segment, two other types of tricoid sensilla were still observed. The three antennal segments were shown to be coved by smaller spinules of the microtrichia type. No type of sensillum was seen in the aristas of C. hominivorax. Consistent differences between the sexes in typology, topography, and quantity of antennal sensilla were verified. The great variety of sensillary subtypes, presenting wall pores and/or grooves, found in the funiculus of C. hominivorax, indicates the olfaction should play an important role in this species behavior and communication. The data of the current study, besides corroborating in the amplification of the morphologic and ultrastructural knowledge of C. hominivorax, can foment future electrophysiological studies for the development of volatile semiochemicals, to be uses as attractants in traps, as a new alternative to monitoring and/or controlling this fly.     

“Deflected” calyx sign

Despite the introduction of nephrotomography and renal angiography, routine excretory urography still is the main diagnostic tool in radiology that provides the necessary evidence for the diagnosis of renal tuberculosis. The “deflected” calyx sign results from stricture of an infundibulum which ultimately leads to complete obstruction and a space-occupying (pseudotumor) mass produced by a debris filled dilated calyx. Since no contrast medium enters the obstructed calyx, the normal middle calyx frequently appears to be “deflected”. When other typical radiographic evidence is absent, this sign should suggest renal tuberculosis.     

Norovirus Infection in Young Nicaraguan Children Induces Durable and Genotype-Specific Antibody Immunity

There are significant challenges to the development of a pediatric norovirus vaccine, mainly due to the antigenic diversity among strains infecting young children. Characterizing human norovirus serotypes and understanding norovirus immunity in naïve children would provide key information for designing rational vaccine platforms. In this study, 26 Nicaraguan children experiencing their first norovirus acute gastroenteritis (AGE) episode during the first 18 months of life were investigated. We used a surrogate neutralization assay that measured antibodies blocking the binding of 13 different norovirus virus-like particles (VLPs) to histo-blood group antigens (HBGAs) in pre- and post-infection sera. To assess for asymptomatic norovirus infections, stools from asymptomatic children were collected monthly, screened for norovirus by RT-qPCR and genotyped by sequencing. Seroconversion of an HBGA-blocking antibody matched the infecting genotype in 25 (96%) of the 26 children. A subset of 13 (50%) and 4 (15%) of the 26 children experienced monotypic GII and GI seroconversion, respectively, strongly suggesting a type-specific response in naïve children, and 9 (35%) showed multitypic seroconversion. The most frequent pairing in multitypic seroconversion (8/12) were GII.4 Sydney and GII.12 noroviruses, both co-circulating at the time. Blocking antibody titers to these two genotypes did not correlate with each other, suggesting multiple exposure rather than cross-reactivity between genotypes. In addition, GII titers remained consistent for at least 19 months post-infection, demonstrating durable immunity. In conclusion, the first natural norovirus gastroenteritis episodes in these young children were dominated by a limited number of genotypes and induced responses of antibodies blocking binding of norovirus VLPs in a genotype-specific manner, suggesting that an effective pediatric norovirus vaccine likely needs to be multivalent and include globally dominant genotypes. The duration of protection from natural infections provides optimism for pediatric norovirus vaccines administered early in life.