Mortality in Patients with Myalgic Encephalomyelitis and Chronic Fatigue Syndrome.

BACKGROUND: There is a dearth of research examining mortality in individuals with myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Some studies suggest there is an elevated risk of suicide and earlier mortality compared to national norms. However, findings are inconsistent as other researchers have not found significant increases in all-cause mortality for patients. OBJECTIVE: This study sought to determine if patients with ME or CFS are reportedly dying earlier than the overall population from the same cause. METHODS: Family, friends, and caregivers of deceased individuals with ME or CFS were recruited through social media, patient newsletters, emails, and advocate websites. This study analyzed data including cause and age of death for 56 individuals identified as having ME or CFS. RESULTS: The findings suggest patients in this sample are at a significantly increased risk of earlier all-cause (M = 55.9 years) and cardiovascular-related (M = 58.8 years) mortality, and they had a directionally lower mean age of death for suicide (M = 41.3 years) and cancer (M =66.3 years) compared to the overall U.S. population [M = 73.5 (all-cause), 77.7 (cardiovascular), 47.4 (suicide), and 71.1 (cancer) years of age]. CONCLUSIONS: The results suggest there is an increase in risk for earlier mortality in patients with ME and CFS. Due to the small sample size and over-representation of severely ill patients, the findings should be replicated to determine if the directional differences for suicide and cancer mortality are significantly different from the overall U.S. population.

Serum-free culture of mid-gestation mouse embryos: a tool for the study of endoderm-derived organs.

The experimental manipulation of mid-gestation mouse embryos is an important tool for the study of developmental biology. However, such techniques can be challenging due to difficulties accessing the embryos in utero, and therefore the ability to maintain mid-gestation mouse embryos in vitro has proved invaluable. Described here is an example of a whole embryo culture system, where a serum-free medium is used to support the development of mouse embryos in vitro from embryonic day 10.5 (E10.5) to E11.5. During this time the embryos increase in size and undergo developmental progression, as determined by morphological and molecular criteria. This makes it an ideal environment in which to support and maintain mid-gestation mouse embryos following experimental manipulations. Two applications of this whole embryo culture system are described here. In the first, protein-soaked beads are carefully positioned in the pharyngeal region of an E10.5 embryo, allowing the concentration of specific proteins to be altered within the tissue. In the second technique, morpholino oligonucleotides are electroporated into the pharyngeal region of the embryo at E10.5, creating an efficient system for the knockdown of gene function in the target cells. These techniques demonstrate the use of in vitro techniques to study organogenesis within the pharyngeal region of the mouse embryo, but with some modification they could be adapted to target any region of the endodermal gut tube.

Mitochondrial retention of Opa1 is required for mouse embryogenesis.

Mitochondria are dynamic cellular organelles that balance fission and fusion to regulate organelle morphology, distribution, and activity, and Opa1 is one of three GTPases known to regulate mitochondrial fusion. In humans, loss of a single Opa1 allele causes dominant optic atrophy, a degenerative condition that leads to loss of vision. Here we demonstrate that the lilR3 mutant mouse phenotype is due to a point mutation in the Opa1 gene resulting in mislocalized Opa1 protein from the mitochondria to the cytosol. Importantly, the mutation is in the middle domain of the Opa1 protein, for which no function had been described. Lack of mitochondrial retention of Opa1 is sufficient to cause the cellular Opa1 loss-of-function phenotype as the mitochondria are fragmented, indicating an inability to fuse. Despite the normally ubiquitous expression of Opa1 and the essential nature of mitochondria, embryos with aberrant Opa1 survived through midgestation and died at E11.5. These mutants displayed growth retardation, exencephaly, and abnormal patterning along the anterior-posterior axis, although the A-P axis itself was intact. The complex relationship between mitochondrial dynamics and cell death is emphasized by apoptosis in specific cell populations of lilR3 embryos. Our results define, for the first time, a function of the middle domain of the Opa1 protein and demonstrate that mitochondrial retention of Opa1 protein is essential for normal embryogenesis.

Hospitalization in HIV in Chicago.

BACKGROUND: Reduction in HIV-related morbidity and mortality in the highly active antiretroviral therapy (HAART) era has been unevenly distributed in the United States, and its impact on hospitalizations in urban minority populations in the public sector has been poorly characterized. METHODS: We conducted a retrospective analysis of clinical and administrative data sets of an urban public hospital HIV clinic from 1997 and 1998 to identify the correlates of hospitalization early in the HAART era. RESULTS: 2,647 unduplicated HIV-infected patients were seen in 1997 and 1998 at the CORE Center. There were 31.7 percent women, 71 percent African-Americans and 12 percent Hispanics, and the mean age was 38 years. Men who had sex with men (MSM), injection drug users (IDU), and heterosexuals each made up one third of the population. A majority of the patients had no health insurance, and 27 percent had Medicaid. The median CD4 T cell count was 266 cells/microL, and the median viral load was 1,901 copies/ml. Hospitalizations declined significantly from 1997 (1,579) to 1998 (1,160). Admissions were confined to 25 percent of clinic patients, and 16 patients (range 8-15) had eight or more admissions. African-Americans and Hispanics had significantly more and longer hospitalizations than whites, but there was no difference by gender. IDUs had significantly more admissions than non-IDUs (28 percent vs. 21 percent respectively). On multivariate analysis, lower CD4 T cell count and higher viral load predicted risk of admission in all periods. Unexpectedly, hospitalization rates were high in patients in the highest baseline CD4 T cell stratum, > 500 cells/ml (45 of 353, 13 percent), and lowest viral load stratum, < 500 copies/ml (103 of 675, 15 percent), and rose from 1997 to 1998. HAART (i.e., 1 or 2 drug regimens) predicted fewer hospitalizations compared to 1 or 2 drug regimens. In a subset of patients who filled prescriptions on site, HAART increased from 72 percent to 85 percent and 1-2 drug regimens fell from 28 percent to 15 percent from 1997 to 1998. Regular care was associated with more frequent hospitalization and more hospital days per admission than no regular care. Hospitalized patients had significantly higher mortality than patients not hospitalized (12 percent vs. 2 percent respectively). CONCLUSION: HIV-related hospitalizations were frequent in the HAART era and decreased over time. Older age, lack of HAART, lower CD4 T cell count, higher viral load, and minority race predicted hospitalization, while gender did not. However, patients with extremely favorable CD4 T cell and viral load counts also had higher than expected hospitalization rates. Three quarters of patients had no hospitalizations, and clustering of hospitalizations in a small number of patients may enable targeted programs to reduce recidivism.