Cerebral autoregulation is preserved in multiple system atrophy: A transcranial Doppler study.

Patients with multiple system atrophy (MSA) present large changes in blood pressure (BP) due to autonomic disturbances. We analyzed how this change may influence dynamic cerebral autoregulation (DCA). Simultaneous recordings of arterial BP (Finapres) and middle cerebral artery (MCA) blood flow velocity (BFV) (transcranial Doppler) were performed in 10 patients with MSA (61 +/- 12 yr of age) and 12 healthy volunteers (61 +/- 11 yr of age): cerebral BFV response to oscillations in mean BP was studied in the supine position by cross-spectral analysis of mean BP and mean MCA BFV. The DCA was also studied during the decrease in BP the first seconds when standing up from a sitting position by the assessment of the cerebrovascular resistance index (CR; mean BP/mean MCA BFV ratio). The MCA BFV/BP cross-spectral analysis showed a phase for the mid-frequency band (0.07-0.2 Hz) significantly larger in MSA, suggesting more active autoregulation in response to larger changes in BP. Changes in CR reflecting the rate of autoregulation, when standing did not differ between the two groups. These data suggest that dynamic cerebral autoregulation is preserved in MSA.     

Multiple sclerosis: genetic versus environmental aetiology: epidemiology in Israel updated

The incidence and prevalence of multiple sclerosis (MS) were compared, controlling for age, in native-born Israelis of different origins and in immigrants to Israel. This comparison was carried out in two populations, countrywide and in Jerusalem. In the countrywide population, ascertainment was based mainly on hospitalizations; it included 252 patients who were native-born and 150 who had immigrated from Africa-Asia (AA immigrants). The 89 MS patients of Jerusalem also included patients diagnosed in outpatient clinics. In native-born Israelis whose father was born in Europe-America (I-EA), the incidence and prevalence of MS were found to be as high as or even higher than that found previously in immigrants from Europe-America. Among native-born Israelis whose father was born in Africa or Asia (I-AA), the yearly age-adjusted incidence and prevalence rates were found to be 1.4- to 1.8-fold higher than among AA immigrants, pointing to environmental factors. The incidence and prevalence rates in the I-EA were 1.2- to 1.6-fold higher than in the I-AA, pointing to genetic factors. These results seem to point to both environmental and genetic factors in the aetiology of MS. Further research is needed, however, to disentangle the genetic factors from possible environmental differences in the two ethnic groups.     

Variability in anticardiolipin antibody detection: role of nonspecific IgG binding and different microtiter plates.

There are many studies that are available on the Internet that attempt to standardize the assay for anticardiolipin antibody evaluation because of the variability of results. The aim of this study was to evaluate simultaneously the role of different microplates and the importance of sample nonspecific binding in determining different results in anticardiolipin antibody detection. Sera from 8 patients with raised levels of IgG anticardiolipin antibodies and 10 control sera were assayed by enzyme-linked immunosorbent assay in the presence (specific binding) or in the absence of cardiolipin (sample blank) with four different microplates, that is, NUNC PolySorp, FALCON ProBIND, Greiner 655061 (high binding), and Greiner 655001 (medium binding). Results were expressed as optical densities or net-optical densities (following sample blank subtraction) as well as international IgG anticardiolipin units (GPL) or net-GPL. A wide interplate variability of optical densities was found. When results were expressed as GPL, significant differences were only found between Greiner 655061, FALCON ProBIND, and NUNC PolySorp (P < .05 and P < .001, respectively) whereas differences were not statistically significant if interplate variability was analyzed as net-GPL. Results expressed as categorical variables (ie, positive/negative, according to a GPL cut-off and net-GPL cut-off, obtained with sera from 100 apparently healthy blood donors) showed a good or excellent Cohen's kappa coefficient of concordance among plates when positivity was evaluated on net-GPL. Our data strongly suggest that quantification and subtraction of sample blank may improve both interlaboratory agreement and reliability of anticardiolipin assay and minimize false-positive results.     

Candidate genes associated with ageing and life expectancy in the Jerusalem longitudinal study

In an exploratory study, 11 common polymorphisms were examined for contributing to longevity including: apolipoprotein E (apoE), methylenetetrahydrofolate reductase (MTHFR), cathepsin D (CAD), superoxide dismutase 2 (SOD2), angiotensinogen (AGT) and insulin-like growth factor 2 (IGF2), Leiden factor 7, p53 oncogene, dopamine D4 receptor (DRD4) and the serotonin transporter (SERT). Genotype and allele frequencies of these genes were compared in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity to a group of 441 younger subjects (22 years). Nominally significant results provide suggestive evidence in the Ashkenazi group that apoE, MHTFR, SOD2, IGF2 ApaI, and factor VII are risk factors for a single outcome, survival to 75. Overall, the more genetically homogenous Ashkenazi ethnic group showed evidence for association in five genes examined suggesting that future studies in this population would gainfully focus on this ethnic group.     

Fatal Dieulafoy's type ulcer in a case of gastric AL-amyloidosis

Dieulafoy's ulcer is a particular form of gastric ulcer confined to a persistent caliber artery and may lead to severe hemorrhage. We report a case of fatal gastric bleeding in a woman with benign biclonal gammapathy. Autopsy found a typical Dieulafoy's ulcer centered by a persistent caliber artery which wall was thickened by AL-amyloid deposits. Amyloidosis involved the gastric wall, but also middle caliber arteries of the liver, the lung, the pancreas, the kidney and the myocardium. AL-amyloidosis is a rare and late complication of monoclonal gammapathy and may be asymptomatic. Pathogenesis of Dieulafoy's ulcer remains unclear. In our case, local ischemia may have facilitated gastric ulceration, and amyloid deposits may have contributed to arterial rupture.     

A cellular model for myeloma cell growth and maturation based on an intraclonal CD45 hierarchy

Summary: Multiple myeloma (MM) is a plasma cell malignancy mainly characterized by the accumulation of malignant plasma cells within the bone marrow. This review shows that the biology of CD45 illuminates that of MM and, more specifically, provides a better delineation of a tumor cell ‘hierarchy’ of clinical interest. We show that in MM, as in normal plasma cell differentiation, there is an intraclonal CD45 hierarchy that is a gradient of CD45 expression on myeloma cells directly related to their proliferation rate and differentiation status. This CD45 hierarchy allows for the design of a cellular model for MM‐cell growth and maturation in which CD45 bright myeloma cells represent the proliferating compartment and CD45 low myeloma cells the quiescent compartment. This model includes an aberrant phenotype that is annihilation rather than decline of CD45, annihilation reflecting the terminal phase of the disease and/or an aggressive presentation of MM. Data from the literature suggest that CD45 bright myeloma cells are targeted by interleukin (IL)‐6, whereas CD45 negative myeloma cells with a high clonogenic capacity are targeted by insulin/insulin‐like growth factor 1 (IGF‐1). This model will be useful for both a better understanding of the basic biology of MM and a better stratification of and therapeutic approach to the patients. Finally, this model presents MM as a self‐renewing plasma cell disease, although the first oncogenic events such as 14q32 translocations clearly occur earlier in a B cell.     

Reproductive genetic counselling in non-mosaic 47,XXY patients: implications for preimplantation or prenatal diagnosis: Case report and review

With an incidence of approximately 1 in 500 male newborns, the 47,XXY genotype is one the most common sex chromosome anomalies. It is also the most frequent genetic cause of human infertility. Some non-mosaic 47,XXY patients have sperm production which allows infertility treatment to be offered by ICSI. Therefore, the risk of transmitting a chromosome anomaly to the next generation is an important problem in reproductive genetic counselling of these patients. Here, we report on a twin pregnancy where two karyotypically normal neonates 46,XX and 46,XY were born after the use of ICSI in assisted reproduction of a patient with a non-mosaic 47,XXY syndrome. To date, only 38 evolving pregnancies including the present cases, have been reported after ICSI using sperm from non-mosaic 47,XXY patients. Although these data are scarce, they suggest that the risk of chromosome anomaly in the offspring of these patients is low; hence, their reproductive genetic counselling can be reassuring, and management of the pregnancy can proceed with caution.     

Trisomy 7 mosaicism, maternal uniparental heterodisomy 7 and Hirschsprung's disease in a child with Silver-Russell syndrome

Prenatal trisomy 7 is usually a cell culture artifact in amniocytes with normal diploid karyotype at birth and normal fetal outcome. In the same way, true prenatal trisomy 7 mosaicism usually results in a normal child except when trisomic cells persist after birth or when trisomy rescue leads to maternal uniparental disomy, which is responsible for 5.5-7% of patients with Silver-Russell syndrome (SRS). We report here on the unusual association of SRS and Hirschsprung's disease (HSCR) in a patient with maternal uniparental heterodisomy 7 and trisomy 7 mosaicism in intestine and skin fibroblasts. HSCR may be fortuitous given its frequency, multifactorial inheritance and genetic heterogeneity. However, the presence of the trisomy 7 mosaicism in intestine as well as in skin fibroblasts suggests that SRS and HSCR might possibly be related. Such an association might result from either an increased dosage of a nonimprinted gene due to trisomy 7 mosaicism in skin fibroblasts (leading to SRS) and in intestine (leading to HSCR), or from an overexpression, through genomic imprinting, of maternally expressed imprinted allele(s) in skin fibroblasts and intestine or from a combination of trisomy 7 mosaicism and genomic imprinting. This report suggests that the SRS phenotype observed in maternal uniparental disomy 7 (mUPD(7)) patients might also result from an undetected low level of trisomy 7 mosaicism. In order to validate this hypothesis, we propose to perform a conventional and molecular cytogenetic analysis in different tissues every time mUPD7 is displayed.     

A member of a conserved Plasmodium protein family with membrane-attack complex/perforin (MACPF)-like domains localizes to the micronemes of sporozoites

Pore-forming proteins are employed by many pathogens to achieve successful host colonization. Intracellular pathogens use pore-forming proteins to invade host cells, survive within and productively interact with host cells, and finally egress from host cells to infect new ones. The malaria-causing parasites of the genus Plasmodium evolved a number of life cycle stages that enter and replicate in distinct cell types within the mosquito vector and vertebrate host. Despite the fact that interaction with host-cell membranes is a central theme in the Plasmodium life cycle, little is known about parasite proteins that mediate such interactions. We identified a family of five related genes in the genome of the rodent malaria parasite Plasmodium yoelii encoding secreted proteins all bearing a single membrane-attack complex/perforin (MACPF)-like domain. Each protein is highly conserved among Plasmodium species. Gene expression analysis in P. yoelii and the human malaria parasite Plasmodium falciparum indicated that the family is not expressed in the parasites blood stages. However, one of the genes was significantly expressed in P. yoelii sporozoites, the stage transmitted by mosquito bite. The protein localized to the micronemes of sporozoites, organelles of the secretory invasion apparatus intimately involved in host-cell infection. MACPF-like proteins may play important roles in parasite interactions with the mosquito vector and transmission to the vertebrate host.     

Intimate partner violence (IPV) and preeclampsia among Peruvian women

OBJECTIVE: Mounting evidence supports the view that intimate partner violence (IPV) is an important cause of maternal mortality. Some, but not all, prior studies suggest that IPV is associated with increased risks of maternal medical conditions such as hypertensive disorders of pregnancy which are leading causes of maternal mortality worldwide. We assessed the relation between IPV and risk of preeclampsia among Peruvian women. STUDY DESIGN: We conducted a case-control study at two large hospitals in Lima, Peru. Preeclampsia cases were 339 women with pregnancy-induced hypertension and proteinuria (i.e., preeclampsia). Controls were 337 normotensive women. Information concerning women's exposure to physical and emotional violence during pregnancy was collected during in-person interviews conducted after delivery and while patients were in hospital. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from logistic regression models. RESULTS: The prevalence of IPV was 43.1% among cases and 24.3% among controls. Compared with those reporting never exposure to IPV during pregnancy, women reporting any exposure had a 2.4-fold increased risk of preeclampsia (OR=2.4; 95% CI: 1.7-3.3). The association was strengthened slightly after adjusting for maternal age, parity and pre-pregnancy adiposity (OR=2.7; 95% CI: 1.9-3.9). Emotional abuse in the absence of physical violence was associated with a 3.2-fold (95% CI: 2.1-4.9) increased risk of preeclampsia. Emotional and physical abuse during pregnancy was associated with a 1.9-fold increased risk of preeclampsia (95% CI: 1.1-3.5). CONCLUSIONS: IPV among pregnant women is common and is associated with an increased risk of preeclampsia. These data support recent calls for coordinated global health efforts to prevent violence against women.