Myelinated nerve fibres in the subcortical white matter of cerebral hemispheres are preserved in alcoholic subjects

Previous studies have found that the primary change in the brain of chronic alcoholics is a selective loss of white matter in cerebral hemispheres. It is unknown whether the loss of white matter is due to alcohol-induced degeneration of axons in white matter, and this hypothesis has never been tested. We used a newly developed stereological method to investigate whether the length and diameter of myelinated fibres change in the subcortical white matter of male alcoholic subjects. We found no significant differences between control and alcoholic subjects with respect to the total volume, total length, and mean diameter of myelinated fibres in white matter. Our results do not find any support for the hypothesis that chronic alcoholic subjects may suffer from a degeneration of axons (myelinated fibres) in white matter in cerebral hemispheres.     

A role for interferon-gamma in focal cerebral ischemia in mice

The pro-inflammatory cytokine interferon-gamma (IFNgamma) has traditionally been associated with inflammatory CNS disease and more recently with ischemia-induced pathology. Using a murine model of focal cerebral ischemia, we found no evidence for induction of IFNgamma mRNA after permanent middle cerebral artery occlusion. In addition, we found that mice deficient in IFNgamma or IFNgamma receptors developed neocortical infarcts similar in size to those in wild type. In contrast, MBP promoter-IFNgamma-transgenic mice consistently developed significantly larger infarcts than non-transgenic mice. Because IFNgamma is a potent activator of microglia-macrophages, we investigated the involvement of microglial-macrophage-derived TNF in the larger infarcts. Numbers of TNF mRNA-expressing microglia-macrophages and levels of TNF mRNA and TNF in IFNgamma-transgenic and non-transgenic mice were similar. Furthermore, the ischemic brain damage in IFN-gamma-transgenic mice was unaffected by recombinant soluble TNF receptor I. Taken together, the data argues against a role for IFNgamma in cerebral ischemia under normal conditions. However, when present, IFNgamma significantly exacerbates ischemia-induced brain damage by mechanisms that appear to be independent of TNF or synergistic neurotoxic interactions of IFNgamma and TNF Irrespective of the mechanism(s) involved, this enhancing effect of IFNgamma on ischemia-induced neurotoxicity may need to be considered in diseases where immune IFNgamma is involved, such as multiple sclerosis.     

Willingness to pay for dental fear treatment

The aim of this paper is to discuss the social desirability of supplying dental fear treatment in addition to dental treatment using the results from a treatment programme for patients with severe dental fear. The programme consisted of three different dental fear treatments: Cognitive therapy, applied relaxation and nitrous oxide sedation, in addition to dental treatment. To evaluate the effects of uncertainty on the patients' benefits from the programme, we elicited their willingness to pay, both before and after receiving treatment, since we expected patients to be uncertain about the outcome of the dental fear treatment. We found that the social desirability of the treatment was very sensitive to uncertainty. While only 24% of the patients were willing to pay the actual cost of the treatment before attending, 71% were willing to pay afterwards. This implies that many patients who would benefit from the treatment ex post are not willing to pay the cost of the treatment ex ante, and will thus not receive any treatment unless it is subsidized.     

Age-related inflammatory cytokines and disease

Aging is associated with chronic low-grade increases in circulating levels of inflammatory markers. A wide range of environmental factors, including smoking, infections, and obesity, genetic factors, and the declining function of sex hormones may contribute to systemic low-grade inflammatory activity in older individuals. Age-associated disease may exacerbate this phenomenon. The multifunctional cytokines TNF-alpha and IL-6 have been associated with morbidity and mortality in the elderly. Evidence supports the direct role of TNF-alpha in the pathogeneses of atherosclerosis, type 2 DM, and AD in older individuals. Age-related increases in systemic levels of TNF-alpha could provide a unifying basis for these disorders. Furthermore, TNF-alpha induces a catabolic state that causes frailty. Circulating levels of IL-6 seem to be a strong risk factor for frailty in the elderly, which could reflect its association with increased production of TNF-alpha. IL-6 also may be a risk factor for thromboembolic complications. In healthy, elderly populations, high circulating levels of TNF-alpha and IL-6 predict mortality, independent of comorbidity, indicating that TNF-alpha and IL-6 cause morbidity and mortality. In cohorts of frail, older individuals, TNF-alpha and IL-6 also act as disease markers. Circulating levels of TNF-alpha seem to be the best predictor of mortality in frail, elderly populations with a high mortality rate, whereas IL-6 seems to be the strongest risk marker in healthy, elderly populations. This finding could reflect that in relatively healthy old populations the increase in circulating levels of IL-6 represent a systemic response to local proinflammatory activities; however, when age-related inflammatory diseases progress, levels of TNF-alpha increase in the circulation and become gradually a stronger risk marker than IL-6. In conclusion low-grade elevations in levels of circulating cytokines are strong independent risk factors of morbidity and mortality in the elderly, and lifestyle factors and comorbidities may modulate these levels. Exercise and dietary interventions may be possible strategies to decrease inflammatory activity and improve the health status of the elderly.     

Multiple telomeric aberrations in a telomerase-positive leukemia patient

Bone marrow samples from a pancytopenia/leukemia patient were routinely analyzed at first and second admission. At the first presentation, the karyotype was normal, whereas 17 months later several chromosome aberrations were recognized including presumed additions to the short arms of chromosomes 1 and 16 in all cells, and numerous other aberrations in subpopulations of cells. From the predominance of aberrations at chromosome ends, we suspected insufficient telomere maintenance as an underlying mechanism behind the karyotype changes, in particular as an interstitial deletion in the region harboring the gene for the RNA component (hTERC) of the telomerase enzyme was also noticed; however, while molecular cytogenetic investigation confirmed the terminal aberrations, we found the malignant cells positive for telomerase activity and the presence of an hTERC gene on both chromosomes 3. A presumed chromosome 1 addition turned out to reflect an amplification of a tandemly repeated sequence element. Labeling of multiple tandem repeat sequences in situ by a novel multicolor primed in situ hybridization showed no evidence of instability of other repeated DNA elements.     

99mTc-aprotinin scintigraphy in amyloidosis.

Changes in the amount and distribution of amyloid lesions have been difficult to monitor because they can usually be demonstrated only by evident symptoms or from a biopsy. The recent progress in the treatment of amyloidosis stresses the need for an early diagnosis and the need for noninvasive monitoring during the course of treatment. To validate (99m)Tc-aprotinin scintigraphy, we studied 23 consecutive patients with known or suspected amyloidosis. METHODS: (99m)Tc-Aprotinin (500-700 MBq) was injected intravenously and whole-body scans, regional images, and SPECT tomograms were obtained 90 min after tracer injection. RESULTS: Focal accumulations of (99m)Tc-aprotinin were seen in different organs of 22 patients with a total of 90 lesions, of which 20 were confirmed by biopsy or autopsy. Scintigraphy revealed "silent" amyloid deposits in at least 5 patients who later developed clinical symptoms. Physiologic uptake or excretion in liver and kidneys could not be differentiated from pathologic lesions in those organs. CONCLUSION: (99m)Tc-Aprotinin scintigraphy appears to be a fairly sensitive and specific diagnostic modality in patients with suspected amyloidosis. The technique is noninvasive, and it entails a minimal stress to the patient and is useful for detection of a wide range of lesions.     

Neighborhood environment,racial position,and risk of police-reported domestic violence: a contextual analysis

OBJECTIVES: The purpose of this study was to examine the contribution of neighborhood socioeconomic conditions to risk of police-reported domestic violence in relation to victim's race. Data on race came from police forms legally mandated for the reporting of domestic violence and sexual assault. METHODS: Using 1990 U.S. census block group data and data for the years 1996-1998 from Rhode Island's domestic violence surveillance system, the authors generated annual and relative risk of police-reported domestic violence and estimates of trends stratified by age, race (black, Hispanic, or white), and neighborhood measures of socioeconomic conditions. Race-specific linear regression models were constructed with average annual risk of police-reported domestic violence as the dependent variable. RESULTS: Across all levels of neighborhood poverty (< 5% to 100% of residents living below the federal poverty level), the risk of police-reported domestic violence was higher for Hispanic and black women than for white women. Results from the linear regression models varied by race. For black women, living in a census block group in which fewer than 10% of adults ages > or = 25 years were college-educated contributed independently to risk of police-reported domestic violence. Block group measures of relative poverty (> or = 20% of residents living below 200% of the poverty line) and unemployment (> or = 10% of adults ages > or = 16 years in the labor force but unemployed) did not add to this excess. For Hispanic women, three neighborhood-level measures were significant: percentage of residents living in relative poverty, percentage of residents without college degrees, and percentage of households monolingual in Spanish. A higher degree of linguistic isolation, as defined by the percentage of monolingual Spanish households, decreased risk among the most isolated block groups for Hispanic women. For white women, neighborhood-level measures of poverty, unemployment, and education were significant determinants of police-reported domestic violence. CONCLUSION: When data on neighborhood conditions at the block group level and their interaction with individual racial position are linked to population-based surveillance systems, domestic violence intervention and prevention efforts can be improved.     

Long-term combined supplementations with alpha-tocopherol and vitamin C have no detectable anti-inflammatory effects in healthy men

Inflammatory and oxidative stresses play a pivotal role in atherogenesis. Vitamin E and vitamin C are the two most important dietary antioxidants; moreover, vitamin E has anti-inflammatory effects. Combined supplementations with vitamin E and vitamin C twice daily for 3 y reduced lipid peroxidation and retarded the progression of common carotid atherosclerosis in healthy men in the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study. To further elucidate the underlying mechanisms that retarded the progression of atherosclerosis in the ASAP study, we investigated the effect of a combined intake of vitamin E and vitamin C on inflammatory markers in vivo. Circulating levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and C reactive protein (CRP) were measured in 45- to 69-y-old men from the ASAP study with cholesterol >5.0 mmol/L before and after treatment with either placebo (n = 52) or a combined supplementation with 91 mg (136 IU) alpha-tocopherol and 250 mg of slow-release vitamin C twice a day (n = 55) for 3 y. Antioxidant treatment for 36 mo had no effect on circulating levels of TNF-alpha, IL-6 or CRP. In conclusion, long-term combined supplementations with alpha-tocopherol and vitamin C in reasonable doses have no detectable systemic anti-inflammatory effects in a healthy population of men with slight hypercholesterolemia and no overt signs of inflammation.