Time in hemodialysis modulates the levels of genetic damage in hemodialysis patients

It is assumed that hemodialysis treatment can diminish the levels of genetic damage in circulating lymphocytes by cleaning the blood of uremic toxins that cause oxidative stress. However, the hemodialysis process by itself may also induce genomic damage by producing reactive oxygen species (ROS). We conducted a follow‐up study in a group of 70 hemodialysis patients followed for a mean time of 15 months. We investigated the effect of exposure time in hemodialysis on the levels of genetic damage in peripheral blood lymphocytes using the micronucleus assay. In addition, genetic damage after in vitro irradiation with 0.5 Gy was also analyzed to evaluate changes in radiosensitivity. Our results showed that, at the end of the study, there was a decrease in both the basal levels of genetic damage (9.9 ± 1.0 vs. 7.6 ± 0.7) and radiosensitivity values (38.5 ± 3.0 vs. 27.6 ± 2.4). We conclude that hemodialysis procedures may act as an ameliorating factor reducing the genetic damage present in chronic kidney disease patients. Environ. Mol. Mutagen. 55:363–368, 2014. © 2014 Wiley Periodicals, Inc.     

Genomic damage as a biomarker of chronic kidney disease status

Patients suffering from chronic kidney disease (CKD) exhibit a high incidence of cancer and cardiovascular diseases, as well as high levels of genomic damage. To confirm the association of CKD with genomic damage we have carried out the largest study to date addressing this issue, using a total of 602 subjects (187 controls, 206 pre‐dialysis CKD patients and 209 CKD patients in hemodialysis). DNA oxidative damage was measured in all individuals using the comet assay. Our results indicate that CKD patients have significantly higher levels of DNA damage than controls, but no significant differences were observed between pre‐hemodialysis (pre‐HD) and hemodialysis (HD) patients. When oxidative damage was measured, no differences were observed between patients and controls, although HD patients showed significantly higher levels of oxidative damage than pre‐HD patients. In addition, a positive relationship was demonstrated between genomic damage and all‐cause mortality. Our study confirms that genomic damage can be predictive of prognosis in CKD patients, with high levels of DNA damage indicating a poor prognosis in HD patients. Environ. Mol. Mutagen. 56:301–312, 2015. © 2014 Wiley Periodicals, Inc.     

Meningococcal meningitis with ‘normal’ cerebrospinal fluid

A prospective study was made of all patients with normal CSF counts and positive cultures for Neisseria meningitidis diagnosed in “El Vallés” County, Barcelona between January 1987 and December 1990. Meningococcal meningitis was documented in 82 patients, eight of whom (seven children, five boys and two girls with a mean age of 5·6 ± 3·3 years, and a 69-year-old male patient) had no apparent CSF abnormalities in the initial lumbar puncture. At the time of admission all patients had fever (mean 39·1 °C) of 10·8 ± 5·6 hour duration and petechial rash which had been present for a mean of 3·6 ± 3·3 hours. Signs of meningeal irritation were not found. A 4-month-old infant with symptoms of circulatory collapse, intracranial hypertension and impairment of consciousness subsequently died of septicemia in 48 hours. Group B N. meningitidis was isolated in six cases (reduced penicillin-susceptibility in two cases) and group C N. meningitidis in the remaining two (reduced penicillin-susceptibility in one case). Patients without pleocytosis did not differ in a statistically significant fashion from the patients with high pleocytosis in the duration of temperature, and petechial rash, leukopenia, positive blood culture and fatal outcome.     

Interrelationship between mitosis and endomitosis in cultures of human megakaryocyte progenitor cells [published erratum appears in Blood 1987 May;69(5):1547]

Sera from dogs rendered aplastic by total-body irradiation stimulate human bone marrow megakaryocyte progenitors to form megakaryocyte colonies in plasma clot cultures. In this investigation, we evaluated the effects of varying concentrations of such sera on both the mitotic and endomitotic phases of human megakaryocyte development in vitro. When low concentrations of aplastic canine sera (2.5% to 5.0% [vol/vol]) were added to cultures of human peripheral blood mononuclear cells in place of normal AB serum, megakaryocyte colony formation was augmented fivefold, cell numbers per colony increased approximately 2.5- fold, and the geometric mean megakaryocyte ploidy almost doubled. Further increasing the aplastic canine serum concentration from 10% to 30% (vol/vol) stimulated no additional colony formation. However, there was a further augmentation of cell numbers per colony associated with a progressive decrease in the mean megakaryocyte ploidy. Megakaryocyte cultures were harvested after 7, 12, 15, and 19 days of incubation, and these demonstrated that the lower mean ploidy values found at the higher concentrations of aplastic canine serum did not result from delayed endoreduplication. At all aplastic serum concentrations evaluated, there existed a strong correlation between nuclear ploidy and cell diameter. We conclude that both the mitotic and endomitotic events in human megakaryocytopoiesis may be influenced by a factor or factors present in aplastic canine serum. At lower in vitro concentrations, such sera stimulate both mitosis and endomitosis, which promotes the development of megakaryocyte colonies composed of larger cells with a higher mean ploidy. With increasing aplastic serum concentrations, colony formation plateaus and mitosis is favored over endomitosis. This results in colonies composed of more numerous but smaller megakaryocytes with a lower mean ploidy. Our data suggest that the size and extent of polyploidization that can be achieved by a developing megakaryocyte may be influenced by the mitotic prior history of its immediate precursor cell.     

Probability of liver cancer and survival in HCV-related or alcoholic-decompensated cirrhosis. A study of 377 patients.

BACKGROUND: Although chronic alcohol intake and chronic hepatitis C may progress to cirrhosis and hepatocellular carcinoma (HCC), few data are available about survival and probability of developing HCC in decompensated cirrhosis of both aetiologies. METHODS: This study identified factors related with probability of developing HCC and survival in a cohort of 377 consecutive patients with decompensated HCV-related cirrhosis (200 cases) or alcoholic cirrhosis (177 cases) without known HCC, hospitalized for their first hepatic decompensation, as well as to evaluate differences between both aetiologies. Patients were followed for a mean period of 39 +/- 2 months. RESULTS: During follow-up, 42 patients (11.1%) developed HCC (16.5% vs 5.1%) in groups HCV and alcohol, respectively; p = 0.0008), and 131 patients (34.7%) died (42% vs 26.6% in groups HCV and alcohol, respectively; p = 0.002). Age and HCV-cirrhosis were independently related to HCC development, while baseline age and Child-Turcotte-Pugh score were independently correlated with survival. CONCLUSION: Survival in decompensated HCV-related or alcoholic cirrhosis is influenced by age and baseline Child-Turcotte-Pugh score, without differences in cirrhosis aetiology. The risk of developing HCC is greater in HCV-related cirrhosis than in alcoholic cirrhosis.     

The prevention of osteoporosis and sarcopenia in older adults

Osteoporosis and sarcopenia are common in older adults. Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Bone fractures can result in changes in posture, pain, the need for surgical repair and functional impairment. Sarcopenia is the progressive and generalized loss of skeletal muscle mass, strength and/or physical performance. Older adults with sarcopenia experience increased risk of frailty, disability, hospitalizations, mortality, and a reduced quality of life. In this narrative review we provide guidance regarding the prevention of both osteoporosis and sarcopenia, including interventions that prevent both conditions from occurring, recommended screening and treatment to prevent progression.     

Anticardiolipin antibodies and acquired immunodeficiency syndrome: Prognostic marker or association with HIV infection?

Summary Anticardiolipin antibodies (ACA) frequently appear in patients with autoimmune disorders such as systemic lupus erythematosus, and have also been detected in infections, neoplasia, the primary antiphospholipid syndrome, in association with certain medications and also in subjects without apparent disease. Recently, anticardiolipin antibodies have been described in the acquired immunodeficiency syndrome. Eighty-four human immunodeficiency virus (HIV)-infected patients were studied to assess the influence of risk factors for HIV infection and of the stage of HIV-1 infection on the prevalence of IgG-ACA in HIV-seropositive patients. Patients were divided in two groups, one composed of 38 asymptomatic HIV-infected individuals and the other of 46 AIDS patients. A control group of 42 healthy HIV-negative blood donors was also studied. All subjects of the control group were IgG-ACA-negative. Of the 84 HIV-positive patients, 50 were IgG-ACA positive (59.5%) and 34 IgG-ACA negative (40.5%). None of the HIV-positive patients presented any thromboembolic phenomena. No significant differences were found with respect to sex, risk factors and stage of disease when the presence of IgG-ACA in HIV-positive patients was considered. ACA does not appear to be a pronostic marker in HIV-1-infected subjects. The presence of IgG-ACA is probably related to HIV-1-infection itself, and is indicative of impaired humoral immunity in these patients.

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Anticardiolipin-Antikörper und erworbenes Immunschwächesyndrom: Prognostischer Marker oder Assoziation mit HIV-Infektion?

Zusammenfassung Anticardiolipin-Antikörper (ACA) treten häufig bei Patienten mit Autoimmunkrankheiten wie Lupus erythematodes auf, wurden aber auch im Zusammenhang mit Infektionen, Neoplasien, dem primären Antiphospholipid-Syndrom und bestimmten Medikamenten beobachtet oder bei Personen ohne jegliche erkennbare Erkrankung. Kürzlich wurden Anticardiolipin-Antikörper bei erworbener Immunschwäche beschrieben. Um den Einfluß von Risikofaktoren für eine HIV-Infektion und des Krankheitsstadiums auf die Prävalenz von IgG- ACA zu ermitteln, wurden 84 HIV-infizierte Patienten untersucht. Sie wurden in zwei Gruppen, 38 asymptomatische HIV-Infizierte und 46 AIDS-Patienten unterteilt und mit einer Kontrollgruppe von 42 gesunden, HIV-negativen Blutspendern verglichen. Die Kontrollpersonen waren alle ACA-negativ. Aus der Gesamtgruppe der 84 HIV-positiven Patienten wiesen 50 ACA-IgG auf (59,5%), 34 waren negativ (40,5%). Thromboembolische Phänomene waren bei keinem dieser HIV-positiven Personen zu beobachten. Es bestand keine signifikante Differenz zwischen positiven und negativen ACA-Befunden hinsichtlich Geschlecht der Patienten, Risikofaktoren und Krankheitsstadium der HIV- Infektion. Bei HIV-1-Infizierten scheint der Nachweis von ACA keine prognostische Bedeutung zu haben. Die Antikörper sind wahrscheinlich mit der HIV-Infektion selbst assoziiert und ein Zeichen für die gestörten humoralen Immunfunktionen dieser Patienten.