Comparison of sleep-disordered breathing among healthy elderly in the seventh, eighth, and ninth decades of life

We investigated the prevalence of sleep-disordered breathing (SDB) in healthy 80 year-old subjects (n = 38) as compared with healthy 70-(n = 33) and 60-year-old subjects (n = 34). The apnea-hypopnea index (AHI) increased significantly across decades: 39.5% (15 of 38) of 80 year olds, 33.3% (11 of 33) of 70 year olds, and 2.9% (1 of 34) of 60 year olds had an AHI greater than or equal to 5 (chi 2 = 14.0, p less than 0.001). The prevalence of SDB as measured by a more stringent apnea index criterion of greater than or equal to 5 was 18.9% of those in their 80s, 12.1% in their 70s, and 0% in their 60s (chi 2 = 6.63, p less than 0.05). Significant gender differences were noted in the proportion of subjects with AHI greater than or equal to 10: 22.4% of men versus 5.4% of women (chi 2 = 4.25, p less than 0.05). These data suggest that SDB increases with advancing age even in the healthy elderly and may be more marked in healthy men than women.     

Brain structure in men remains highly heritable in the seventh and eighth decades of life

The midsagittal cross-sectional dimensions of the corpus callosum, the coronal cross-sectional area of the lateral ventricles at the level of the pons, and a three-dimensional estimate of intracranial volume were derived from magnetic resonance brain images obtained from 45 monozygotic and 40 dizygotic male twin pairs aged 68 to 78. Univariate genetic analyses indicated strong genetic influences contributing significantly to the variability of each brain structure. The estimated proportion of genetic variance (i.e. heritability) was 81% for intracranial volume, 79% for the midline cross-sectional area of the corpus callosum, and 79% for lateral ventricle size. There was no evidence that shared environmental influences contributed significantly to twin-pair similarities. We further used bivariate genetic modeling to estimate the genetic and environmental correlation between correlated brain structures. Intracranial volume and corpus callosum area was highly correlated, and this relationship was entirely due to shared genetic effects between these two brain structures. By contrast, the relationship between the height of the corpus callosum and the size of the lateral ventricles was due to both genetic and environmental influences in common. Corresponding genetic and environmental correlations were 0.68 and 0.58, respectively, indicating that more than half of the genetic and environmental influences on these two brain structures were shared. The manner in which the brain responds to the environment with advancing age is highly genetically determined, both for the lateral ventricles, which dilate with aging and disease, and for the corpus callosum, which is deformed in shape by age-related ventricular enlargement, whereas its midline cross-sectional area remains unchanged.     

Biparental inheritance of mitochondrial DNA in humans is not a common phenomenon

PurposeA recent report has raised the possibility of biparental mitochondrial DNA (mtDNA) inheritance, which could lead to concerns by health-care professionals and patients regarding investigations and genetic counseling of families with pathogenic mitochondrial DNA variants. Our aim was to examine the frequency of this phenomenon by investigating a cohort of patients with suspected mitochondrial disease.MethodsWe studied genome sequencing (GS) data of DNA extracted from blood samples of 41 pediatric patients with suspected mitochondrial disease and their parents.ResultsAll of the mtDNA variants in the probands segregated with their mother or were apparently de novo. There were no variants that segregated only with the father and none of these families showed evidence of biparental inheritance of their mtDNA.ConclusionPaternal mitochondrial transmission is unlikely to be a common occurrence and therefore at this point we would not recommend changes in clinical practice.     

Lack of endotoxin tolerance with respect to TNF alpha production in the subarachnoid space

To study endotoxin tolerance in the subarachnoid space 0.1 mg of endotoxin derived from Neisseria meningitidis was injected intracisternally into rabbits on 2 consecutive days. On day 1 the maximum peak level of TNF alpha was 7 ng/ml 2 h after injection, whereas on day 2 the highest levels were 3.6 ng/ml and 3.7 ng/ml, respectively, 1 and 2 h after injection. Pretreatment with intravenous endotoxin 5 or 21 h before consecutive intracisternal endotoxin did not affect the cerebrospinal fluid (CSF) levels of TNF alpha. In contrast, there was a marked endotoxin tolerance with respect to TNF alpha in the systemic circulation. Cells appearing in the CSF 5, 12 and 20 h after intracisternal injection of endotoxin were harvested, cultured, and then stimulated with 0.1 mg/ml of endotoxin. In 10 experiments a marked TNF alpha production in the range 10-70 ng/ml was detected in the supernatants, whereas unstimulated cells did not produce TNF alpha. We conclude that tolerance to endotoxin does not develop in the subarachnoid space as evaluated by the present experimental design. The pattern of TNF alpha production and endotoxin tolerance is distinctly different in the subarachnoid space and systemic circulation.     

Evidence that Tumour Necrosis Factor (TNF) is not Constitutively Present in Vivo The Association of TNF with Freshly Isolated Monocytes Reflects a Rapid in Vitro Production

Tumour necrosis factor (TNF) cytotoxic activity has been shown not to be present in detectable amounts in the serum of healthy humans, but it may be found in some patients with menin-gococcal disease. In this study we investigated whether TNF is constitutively present in vivo on or within monocytes. TNF was detected on freshly isolated paraformaldehyde-fixed monocytes from both healthy individuals and cancer patients. No significant difference was found between the two groups. TNF appeared first 40–60 min after in vitro monocyte adherence, which is the same time as it look TNF to appear extracellularly after the exposure of in vitro cultured monocytes to lipopolysaccharide (LPS). This indicates that TNF associated with freshly isolated monocytes was synthesized in vitro. The inducing signal may be monocyte contact with plastic. Exposure of whole blood to LPS immediately after vein puncture was followed by about twice as rapid TNF release as that observed with in vitro cultured monocytes. The release was inhibited by cycloheximide but not by actinomycin D, indicating that the TNF detected did not represent TNF present in vivo. This is consistent with the fact that no TNF cytotoxic activity was detected in blood cell extracts. However, TNF-mRNA may have been present in vivo. Thus, the available evidence indicates that TNF is not constitutively expressed in vivo.     

Chloroquine-induced inhibition of the production of TNF, but not of IL-6, is affected by disruption of iron metabolism.

There is now considerable evidence that cerebral malaria may be related to the over-production of tumour necrosis factor (TNF). Nevertheless, our knowledge is very poor concerning the biological events which lead up to this TNF over-production. Furthermore, interleukin-6 (IL-6) is produced in large amounts during malaria infection and seems to have inhibitory action on TNF production. Anti-malarial drugs were investigated for their ability to interfere with TNF and IL-6 secretion by human non-immune macrophages stimulated by lipopolysaccharides (LPS) or Plasmodium falciparum culture supernatant. Macrophages were pretreated with chloroquine, quinine, proguanil, mefloquine or halofantrine before stimulation. TNF and IL-6 production were suppressed in a dose-dependent manner when macrophages were treated with chloroquine, but not with other anti-malarial drugs. Considering that chloroquine probably acts via lysosomotropic mechanisms, and that iron metabolism may interfere with the non-specific immune response, we focused our attention on these biochemical events in order to investigate the mechanisms by which chloroquine inhibits cytokine production. Our results demonstrated that chloroquine-induced inhibition of TNF and IL-6 production is not mediated through a lysosomotropic mechanism, and that chloroquine probably acts on TNF secretion by disrupting iron homeostasis. Inhibition of IL-6 production seems not to be mediated through these pathways. These observations suggest that chloroquine may help to prevent cerebral malaria whatever the drug sensitivity of the parasite strain, and may provide new tools for an anti-disease therapy regardless of the emergence of parasite multi-drug resistance.     

The impact of a discrepancy between actual and preferred living arrangements on life satisfaction among the elderly in China

OBJECTIVES:

To explore the effects of a discrepancy between actual and preferred living arrangements on the relationship between living arrangements and life satisfaction among the elderly in China.

METHODS:

Secondary analysis of the 2005 dataset of the Chinese Longitudinal Healthy Longevity Survey was performed. A binary logistic regression model was used to analyze the relationship between life satisfaction and living arrangements.

RESULTS:

Among those with concordant actual and preferred living arrangements, living in a nursing home increased the likelihood of life satisfaction, whereas living alone and living with a spouse decreased the likelihood of life satisfaction compared to living with the next generation and a spouse. Among those with discordant living arrangements, there were no differences in life satisfaction between the various living arrangements, except that living with a spouse increased life satisfaction compared to living with the next generation and a spouse.

CONCLUSIONS:

A discrepancy between actual and preferred living arrangements modifies the relationship between life satisfaction and actual living arrangement. Living in a nursing home is a good option for Chinese elder care only if the older individual emotionally accepts it. Living alone or with a spouse is not a good arrangement for elder care, even though it is often preferred by the elderly. Those with discordant living arrangements are more satisfied living with their spouses.     

癌症患者心理适应与生命质量的关系

癌症作为一个重大的生活事件,对患者的身体和情绪产生巨大影响,而如何看待和应对癌症对于患者的康复具有重要的意义[1].本文探查癌症患者心理适应状况及与生命质量的关系,有针对性地对癌症患者进行心理适应状况的干预,以利于癌症患者的临床治疗.     

Serum TNF alpha in mouse typhoid and enhancement of a Salmonella infection by anti-TNF alpha antibodies.

Tumour necrosis factor alpha (TNF alpha) was detected by the L929 cell assay in the sera of mice 1 h after large i.v. inocula of virulent Salmonella typhimurium C5. TNF alpha was not detectable in sera from innately susceptible BALB/c mice during the course of a lethal infection commencing from a low inoculum, or from resistant A/J mice during the course of a lethal or sublethal infection, but only 1 h after i.v. challenge with large numbers of organisms. Administration of a single dose of rabbit polyclonal anti-TNF alpha antiserum on day 1 had no effect on the early course of a lethal infection in A/J mice. However, the same treatment exacerbated a sublethal infection in A/J mice. Anti-TNF alpha treatment did not accelerate the early bacterial net growth rate in the RES. Instead, the cfu count in treated mice continued to increase past the point at which the host response suppressed a further increase in bacterial numbers (the plateau phase) in normal controls. A second dose of anti-TNF alpha antiserum on day 4 together with a higher but still sublethal challenge caused a lethal infection in A/J mice. The results indicate that TNF alpha is important in mediating the plateau phase in a salmonella infection, and its effect may be local.     

The role of TNF alpha polymorphism and expression in susceptibility to nasal polyposis

Objective: In this study, we first performed a meta-analysis to assess the role of single-nucleotide polymorphism (SNP) within tumor necrosis factor alpha (TNF alpha) gene and TNF alpha expression in the risk of nasal polyposis.

Methods: STATA 12.0 software was utilized to conduct the Mantel–Haenszel statistics, Cohen statistics, Begg’s test, Egger’s tests and sensitivity analysis.

Results: We systemically carried out the database retrieval and initially identified 486 articles. After screening, 15 articles were included in our meta-analysis. For TNF alpha rs1800629 G/A SNP, compared with control group, an increased risk of nasal polyposis of case group was observed in the models of A vs. G [p (P value of association) = 0.009, OR (odds ratio) = 1.35], GA vs. GG (p = 0.001, OR = 1.69), GA+AA vs. GG (p = 0.010, OR = 1.47). The similar results were observed in Caucasian subgroup (p < 0.05, OR > 1). For TNF alpha rs361525 G/A SNP, no significant difference between control and case group was detected (all p > 0.05). In addition, a significant difference exists between case and control groups in the meta-analyses of TNF alpha expression in nasal mucosal cells, secreted TNF alpha (p < 0.05, OR > 1), but not serum TNF alpha (p = 0.090).

Conclusion: The present meta-analysis revealed that TNF alpha rs1800629, increased TNF alpha expression and secretion of nasal mucosal cells were associated with an increased risk of nasal polyposis.     

Postnatal upregulation of alpha4 and alpha3 nicotinic receptor subunits in the brain of alpha7 nicotinic receptor-deficient mice

The nicotinic receptor subtypes are important for several physiological functions in brain and may therefore play a critical role in brain development. The alpha7 nicotinic receptors which have high Ca2+ permeability are important for cognitive, neuroprotective and trophic functions. In this study, the brain development and the expression of alpha4, alpha3, alpha7, alpha5 and beta2 nicotinic receptors were investigated in the brains of alpha7 deficient (alpha7 -/-), alpha7 heterozygous null (alpha7 +/-) and alpha7 wild-type (alpha7 +/+) mice from postnatal days (P) 7-84. The specific binding of [3H] cytisine and [3H] epibatidine, as well as the expressions of alpha4 and alpha3 nicotinic receptor subunits at mRNA and protein levels, were significantly increased in the cortex and hippocampus of alpha7 -/- and alpha7 +/- mice compared with alpha7 +/+ mice. Furthermore, the alpha4 and alpha3 nicotinic acetylcholine receptor (nAChR) subunits appeared to co-assemble with the alpha5 nAChR subunit in these above brain regions of these mice. No significant change in synaptophysin level was observed. These data suggest that increased levels of alpha4, alpha3-containing nAChRs, co-assembled with the alpha5 nAChR subunit, may contribute to the normal brain development of alpha7 -/- and alpha7 +/- mice.     

Hematologic interactions of endotoxin, tumor necrosis factor alpha (TNF alpha), interleukin 1, and adrenal hormones and the hematologic effects of TNF alpha in Corynebacterium parvum-primed rats

Endotoxin reduces the release among other cytokines of tumor necrosis factor (TNF) and interleukin 1 (IL-1) and causes peripheral lymphopenia and a dose-response-dependent initial neutropenia followed by a monophasic neutrophilia. TNF alone induces lymphopenia and an initial neutropenia followed by a biphasic neutrophilia. IL-1 alone induces lymphopenia and a monophasic neutrophilia. TNF-plus-IL-1 caused a greater lymphopenia than either monokine alone, suggesting that both monokines contribute to LPS-induced lymphopenia. TNF-plus-IL-1 induced neutropenia similar in magnitude to that induced by TNF alone and induced a neutrophilia significantly greater than that induced by either monokine alone, suggesting that LPS-induced neutropenia is caused by TNF, while LPS-induced neutrophilia is due to the combined effects of TNF and II-1. TNF and IL-1 were administered together with LPS to simulate the in vivo condition of endogenous monokine release during gram-negative bacteremia. TNF combined with LPS increased both the duration and magnitude of LPS-induced lymphopenia, LPS-induced neutropenia, and LPS-induced neutrophilia. TNF-plus-LPS treated rats at 2 hours after injection exhibited a striking 93% decrease in bone marrow neutrophils even though no peripheral neutrophilia was yet apparent, suggesting that the subsequent neutrophilia was due to demargination and recirculation of neutrophils sequestered in the peripheral vasculature immediately after their release from the bone marrow. Epinephrine, which causes neutrophilia by demargination but not by release of marrow neutrophils, reversed the initial neutropenia in TNF-plus-LPS-treated rats and increased the neutrophilia. IL-1 combined with LPS increased LPS-induced neutrophilia, suggesting that endogenous IL-1 also contributed to LPS-induced neutrophilia. Corynebacterium parvum-primed rats with hyperplasia of the monocyte-macrophage system and treated with TNF differed from naive rats treated with TNF in that the second peak was as great as the initial peak of neutrophilia, supporting the hypothesis that the second peak of TNF-induced neutrophilia is due to the release of endogenous monokines. In conclusion, exogenous TNF, IL-1, and adrenal hormones affect circulating numbers of lymphocytes and neutrophils in a fashion consistent with their postulated endogenous role in the regulation of leukocyte trafficking during bacterial infection.     

老年高血压合并抑郁患者生命质量与社会支持关系的研究

目的了解老年高血压合并抑郁患者生命质量与社会支持的关系。方法对28例老年高血压合并抑郁患者（实验组）和45例高血压无抑郁患者（对照组）进行汉密尔顿抑郁量表（HAMD）、生命质量量表及社会支持评定量表的测定,分析生命质量与社会支持的相关性。结果老年高血压合并抑郁患者生命质量的生理功能、生理角色功能、躯体疼痛、总体健康、活力、社会功能、情感职能和心理健康8个维度及总分得分均较对照组降低,差异有统计学意义（P〈0.01）;客观支持、主观支持和社会支持总分分别为（6.78±2.02）、（20.12±3.41）、（32.70±7.72）分,均较对照组降低（P〈0.01）;社会支持与生命质量呈正相关（r=0.542,P〈0.01）。结论应加强对老年高血压合并抑郁患者的社会支持功能,提高生命质量。     

TNF-induced enterocyte apoptosis in mice is mediated by the TNF receptor 1 and does not require p53

Injection of recombinant mouse TNF into mice is known to induce a shrinkage of the duodenal villi, which becomes evident 30 – 90 min later and is associated with a detachment of enterocytes in the lumen. These cells can be collected by lavage and are all apoptotic, i.e. hypodiploid as seen by flow cytometric analysis. Thus the count of detached cells was used as an evaluation of the TNF-induced cell loss and apoptosis in the mucosa. TNF injection induced a cell loss of similar magnitude in wild-type (+/+) or in mice lacking the TNF receptor (TNFR)2 (p75, TNFR2 −/−), while mice lacking the TNFR1 (p55, TNFR1 −/−) were completely resistant to this effect. TNF increased the expression of p53 tumor suppressor gene in the enterocytes from the crypts but not from the villi, as seen by Western blots and histochemistry. TNF increased the expression of p53 in both TNFR2 −/− and TNFR1 −/− mice. Furthermore, enterocyte cell loss was not attenuated in p53 −/− mice. The results indicate that TNF, acting on its receptor 1, induces an apoptotic detachment of the enterocytes from the tip of the villi ( i.e. the old enterocytes), while in the enterocytes from the crypts (the young enterocytes) TNF increases, via either TNFR1 or TNFR2, the expression of p53, without inducing apoptosis.     

Histamine (HA) suppresses the production of tumor necrosis factor alpha (TNFα) in cultured astroglial cells

Inflammation Research -     

Tumor necrosis factor alpha is not implicated in the genesis of experimental autoimmune gastritis

Experimental autoimmune gastritis (EAG) characterised by mononuclear cell infiltrate, parietal and zymogenic cell destruction and circulating autoantibodies to gastric H(+)/K(+)ATPase is an animal model for human autoimmune gastritis, that leads to pernicious anaemia. We have previously shown that Fas has a role in initiating damage to target cells in EAG. Here we used three strategies to examine the role of TNFalpha in this disease. We administered neutralising anti-TNFalpha antibody either as a single injection or as twice weekly injections for 8 weeks to mice subjected to neonatal thymectomy-induced EAG. To address the role of apoptotic signals through TNFR1, TNFR1 deficient mice were either neonatally thymectomised or crossed to PC-GMCSF transgenic mice that spontaneously develop EAG. Neonatally thymectomised mice treated with anti-TNFalpha antibody developed destructive gastritis and autoantibodies to gastric H(+)/K(+)ATPase similar to control mice. Following either neonatal thymectomy or crossing to PC-GMCSF transgenic mice, TNFR1 deficient mice developed autoantibody-positive destructive gastritis at similar frequency compared with wild type and heterozygous littermates. Our observations that neutralisation of TNFalpha and absence of TNFR1 has no discernible effect on development of EAG suggest that TNFalpha is not required for mucosal cell damage or development of autoimmune gastritis. While blocking TNFalpha activity has therapeutic benefit in certain autoimmune diseases, this is not the case for EAG.     

Maternal, perinatal and infant outcome of spontaneous pregnancy in the sixth decade of life

Pregnancy in the older woman is a well-known risk factor for perinatal morbidity and mortality. OBJECTIVE: To evaluate perinatal and infant morbidity and mortality in women 50 or more years old. METHODS: A retrospective population based study (1990-2004) evaluating spontaneously pregnant Chilean women more than 50 years old (217 live or stillbirths) compared to women 20-34 years old (2,817,742 neonates, control group). The comparison was performed using Chi Square with Yates's correction or exact Fisher test as appropriate. The risk analysis was performed by odds ratio (OR) and confidence interval of 95% (CI 95%). RESULTS: Women over 50 had a significantly greater risk of fetal (OR: 3.7; CI 95%: 1.2-10.5), neonatal (OR: 10.4; CI 95%: 5.7-18.7), post-neonatal (OR: 9.5; CI 95%: 4.6-19.1) and infant death (OR: 10.5; CI 95%: 6.6-16.7). There were no differences between groups in the incidences of low and very low birth weight. CONCLUSION: Pregnancy over 50 years of age entails a very high risk of fetal, neonatal and early childhood death. Unprotected sexual life for these women should be considered only after evaluation of their potential fertility.     

TNF alpha, IL-1 alpha and bFGF are implicated in the complex disease of GM-CSF transgenic mice.

Transgenic mice aberrantly expressing the granulocyte-macrophage colony stimulating factor (GM-CSF) gene develop an unusual syndrome of blindness, tissue damage and wasting which is associated with accumulations of hemopoietic cells. In order to further characterize this disease state, we have used messenger RNA detection techniques to show that the genes for tumor necrosis factor (TNF alpha), interleukin-1 alpha (IL-1 alpha) and basic fibroblast growth factor (bFGF) are expressed at abnormally high levels in both macrophages and granulocytes in transgenic mice. Furthermore, since these cell types also express the GM-CSF transgene, it is likely that they are autocrine stimulated by GM-CSF. These observations raise the possibilities that, first, the expression of tumor necrosis factor alpha, interleukin-1 alpha and basic fibroblast growth factor in hemopoietic cells is a direct consequence of their autostimulation by GM-CSF, and second, that these cytokines may be responsible for some aspects of the transgenic mouse disease.     

Clostridium difficile is not associated with outbreaks of viral gastroenteritis in the elderly in the Netherlands

The coincidental increase in norovirus outbreaks and Clostridium difficile infection (CDI) raised the question of whether these events could be related, e.g. by enhancing spread by diarrhoeal disease outbreaks. Therefore, we studied the prevalence of C. difficile in outbreaks of viral gastroenteritis in nursing homes for the elderly and characterised enzyme immunoassay (EIA)-positive stool samples. Stool samples from nursing home residents (n = 752) in 137 outbreaks of viral aetiology were investigated by EIA for the presence of C. difficile toxins. Positive samples were further tested by a cell neutralisation cytotoxicity test, a second EIA and culture. Cultured isolates were tested for the presence of toxin genes, the production of toxins and characterised by 16S rRNA polymerase chain reaction (PCR) and sequencing. Twenty-four samples (3.2%) tested positive in the EIA. Of these 24 positive samples, only two were positive by cytotoxicity and three by a second EIA. Bacterial culture of 21 available stool samples yielded a toxinogenic C. difficile PCR ribotype 001 in one patient sample only. In conclusion, we found no evidence in this retrospective study for an association between viral gastroenteritis outbreaks and C. difficile. The high rate of false-positive EIA samples emphasises the need for second confirmation tests to diagnose CDI.