Interleukins 2 and 12 produce recovery of cytotoxic function in tributyltin-exposed human natural killer cells

Cytotoxic function of human natural killer (NK) cells is modulated by a variety of cytokines. Interleukins (IL) 2 and 12 are both potent stimulators of NK cell cytotoxic function. Tributyltin (TBT) is used in a variety of consumer products and industrial applications. TBT is found in dairy products, meat, and fish. We and others have shown that there are measurable levels of TBT in human blood. Butyltins appear to increase the risk of cancer and viral infections in exposed individuals. We have demonstrated that the ability of NK cells to kill tumor cells is greatly diminished after a l-h exposure to TBT and that this inhibition persists even after removal of the compound. In the current study we examine the effects of the NK-stimulatory ILs, IL2 and IL12, on the ability of NK cells to recover from the persistent inhibitory effects of a 1-h TBT treatment. Highly purified NK cells (> 95% CD16(+)) or a lymphocyte preparation containing both T lymphocytes and NK cells were treated with 300 nM TBT and then allowed to recover for 24 h, 48 h, 4 days, and 6 days in TBT-free media containing no interleukin, 1000 U/mL IL2, 20 ng/mL IL l2, or a combination of IL2 plus IL12. Tumor killing function was then tested using a radioactive chromium release assay. As seen in our previous studies there is no recovery of NK cell cytotoxic function even after a 6-day recovery period when no interleukin is present in the medium. However, there is significant recovery of NK cytotoxic function when IL2, IL12, or the combination of IL2 plus IL12 is present in the medium during the recovery period.     

Interleukins 2 and 12 produce significant recovery of cytotoxic function in dibutyltin-exposed human natural killer cells

Cytotoxic function of human natural killer (NK) cells is modulated by a variety of cytokines. Interleukins (IL) 2, 12, 15, and 18 and Interferon gamma (IFNgamma) are potent stimulators of NK cell cytotoxicity. Butyltins (BTs) are used in a variety of consumer products and industrial applications. Dibutyltin (DBT) is found in plastic products, beverages stored in PVC pipes during manufacturing, and poultry products. BTs appear to increase the risk of cancer and viral infections in exposed individuals. Recently, we have demonstrated that the ability of NK cells to kill tumor cells is greatly diminished after a 1-h exposure to dibutyltin. This inhibition of tumor killing function continues even after removal of the compound. There is no significant recovery of NK cytotoxic function even when the cells are allowed to recover for 6 days. In the current study we examine the effects of NK-stimulatory cytokines on the ability of NK cells to recover from the inhibitory effects of a 1-h DBT treatment. Highly purified NK cells (>95% CD16(+)) or a lymphocyte preparation containing both T lymphocytes and NK cells were treated with 5 microM DBT and then allowed to recover for 24 h, 48 h, 4 days, and 6 days in DBT-free medium containing either no cytokine or a maximally stimulatory dose of several NK-stimulatory cytokines. Tumor killing function was tested using a radioactive chromium release assay. As seen in our previous studies there is no recovery of NK cell cytotoxic function even after a 6-day recovery period when no cytokine is present in the medium. However, there is significant recovery of NK cytotoxic function when IL2, IL12, or the combination of IL2 plus IL12 is present in the medium during the recovery period. The other cytokines tested (IL15, IL18, and IFNgamma) were unable to increase the cytotoxicity of DBT-exposed NK cells.     

Do written action plans improve patient outcomes in asthma? An evidence-based analysis

OBJECTIVE: Current guidelines recommend use of written action plans and peak flow monitoring as key components of asthma care. Our study assesses whether written action plans, with or without peak flow monitoring, have an independent effect on outcomes when used as a component of asthma self-management. STUDY DESIGN: This was a systematic review of published studies. Two independent reviewers followed a prospective protocol for study selection and data abstraction. Outcome data were synthesized qualitatively; they were not appropriate for quantitative meta-analysis. Our comprehensive literature search used MEDLINE, EMBASE, the Cochrane Library, and a hand search of recent bibliographies. The search was limited to full-length, peer-reviewed articles with abstracts in English. The studies were randomized controlled trials that compared the outcomes of an asthma self-management intervention with and without the use a written action plan. The primary outcomes of interest are utilization measures, such as hospitalizations and ER visits. Other outcomes of interest include measures of symptom control and lung function. POPULATION: There were 1501 evaluable patients with asthma; 1410 adults and 91 children. OUTCOMES MEASURED: We measured the frequency of waiting and examination room companions, the reasons for accompaniment, the influence on the encounter, and the overall helpfulness of the companion as assessed by patients and companions. We also determined the physicianamprsquos assessment of the companionamprsquos influence, helpfulness, and behavior during the encounter. RESULTS: Nine randomized controlled trials enrolling a total of 1501 patients met selection criteria. The majority of comparisons in these studies do not demonstrate improved outcomes associated with a written action plan. There are notable methodologic limitations: studies reporting negative findings lack sufficient power, and studies reporting positive findings demonstrate systematic bias. CONCLUSIONS: Although written action plans are widely used, there is insufficient evidence to determine whether their use, with or without peak flow monitoring, improves outcomes.     

2000 National Hospital Discharge Survey

OBJECTIVES; This report presents national estimates of the use of non-Federal short-stay hospitals in the United States during 2000. Numbers and rates of discharges, diagnoses, and procedures are shown by age and sex. Discharges are also shown by geographic region of hospital. Average lengths of stay are presented for all discharges and for selected diagnostic categories by age and by sex. Trend data for selected variables are also provided. METHODS: The estimates are based on medical abstract data collected through the National Hospital Discharge Survey for 2000. The survey has been conducted annually by the National Center for Health Statistics since 1965. Diagnoses and procedures presented are coded according to the International Classification of Diseases, 9th Revision, Clinical Modification, or ICD-9-CM. RESULTS: Trends in the utilization of non-Federal short-stay hospitals show that the rate of hospitalization of the elderly (those 65 years of age and over) increased over the entire period from 1970 to 2000, despite a decrease in the 1980s. The rates for the other age groups declined overall. In 2000, there were an estimated 31.7 million discharges of inpatients, excluding newborn infants, from non-Federal short-stay hospitals in the United States. The discharge rate was 1,140.1 per 10,000 population and the average length of stay was 4.9 days. There were 40 million procedures performed on hospital inpatients during 2000. Males had more cardiovascular procedures than females (3.4 million versus 2.5 million), while females had more operations on the digestive system than males (3.0 million versus 2.2 million). About one-quarter of all procedures performed on females were obstetrical.     

Diabetes mellitus is a risk factor for vascular dementia,but not for Alzheimer's disease: a population-based study of the oldest old

BACKGROUND: The purpose of this study was to examine if Type 2 diabetes mellitus is a risk factor for dementia in very old age, specifically for Alzheimer's disease (AD) and vascular dementia (VaD). METHODS: We evaluated the risk of dementia in relation to Type 2 diabetes using a population-based sample of 702 individuals aged 80 years and older (mean age 83 years). A total of 187 persons received a dementia diagnosis. Thirty-one individuals had a diabetes diagnosis prior to onset of the dementia. RESULTS: Cox proportional hazard analyses, adjusted for age, gender, education, smoking habits, and circulatory diseases, indicated an elevated risk to develop VaD (relative risk = 2.54, 95% confidence interval 1.354.78) in individuals with diabetes mellitus. No association was found between diabetes and AD. CONCLUSION: Type 2 diabetes is selectively related to the different subtypes of dementia. There is no increased risk of AD but more than a twofold risk of VaD in persons with diabetes.     

Telephone screening to identify potential dementia cases in a population-based sample of older adults

This study examined the utility of the TELE, a telephone assessment for dementia, in a sample of 269 individuals that was not selected on the basis of previous dementia diagnosis. Thus, the conditions of the study reflect the actual situation in which a screening instrument might be employed. Scores on TELE were compared to dementia diagnoses. Using the best cutoff score, sensitivity was .86 and specificity was .90. Longitudinal follow-up established that false positives primarily included those who subsequently developed dementia. Telephone screening for dementia has both clinical and research applications. One recommendation based on our experience is that longitudinal studies should include a telephone interview component for anyone who drops out of the study, to enable characterizing the cognitive status of dropouts.     

Reduction in the minimum candidate interval in the dominant-intermediate form of Charcot-Marie-Tooth neuropathy to D19S586 to D19S432

As part of an on-going genomic screen of unlinked Charcot-Marie-Tooth disease type 2 (CMT2) families, we identified 11 regions in the genome with lod scores ≥1.0. One of these regions was near the recently identified CMTDI1 locus on 19q. We show evidence of linkage of DUK 1118 to this region and our data reduce the minimum candidate interval for CMTDI1 to the 9-cM interval spanned by D19S586 and D19S432.We also demonstrate that five additional CMT2 families are unlinked to 19q markers, providing further evidence of CMT2 heterogeneity. Electronic Publication     

Community-based strategies for focus group recruitment of minority veterans

Minority recruitment is crucial to successful clinical research and associated community-based outreach programs. Reaching and retaining a diverse sample is particularly challenging when research targets not only ethnic or racial minorities but also subcultural groups such as veterans of different war periods. We describe various strategies that address the special challenges of minority recruitment through our experience engaging an ethnically diverse sample of 258 veterans as part of an evaluation of ambulatory care services at Department of Veterans Affairs health care facilities. Most veterans were recruited by liaison with the community center, which accounted for 29% of the total sample. Other strategies included on-site recruitment (21%), word of mouth (21%), mailings to veterans' organizations (12%), and newspaper advertisements (7%). Strategies varied in their effectiveness at reaching specific racial or ethnic groups and veterans from different cohorts of war service.     

A comparative multi-laboratory assessment of three factor VIII/von Willebrand factor concentrates

Five expert laboratories have participated in a cross-laboratory study to co-evaluate and compare three commercial Factor VIII/von Willebrand factor (VWF) concentrates. A total of nine factor concentrate lots were evaluated, comprising AHF (High Purity) (AHF HP; x3), Biostate (x3) and Humate/Haemate (x3). All laboratories blind tested for FVIII: C, VWF: Ag and VWF: CB, four tested for VWF: RCo, and one performed VWF: Multimers. The study yielded inter-laboratory CVs for VWF: Ag and FVIII:C around 10-15%, and for VWF:CB and VWF:RCo around 20%, significantly lower than those of previous multi-laboratory surveys. All three lots of AHF HP contained in the vicinity of 25 U/ml FVIII:C, around 60-75 U/ml of VWF:Ag, but only 30-45 U/ml of VWF:CB and 40-50 U/ml of VWF:RCo (thus, CB/Ag ratio around 0.5-0.6 and RCo/Ag ratio around 0.6-0.7). Study determined that FVIII: C and VWF: RCo levels were similar to manufacturer assigned levels. Some loss of the high molecular weight (HMW) multimers was observed, together with an intense low molecular weight (LMW) VWF band consistent with some reduction or proteolysis of HMW VWF. All three lots of Humate/Haemate contained in the vicinity of 23-32 U/ml of FVIII:C, 70-105 U/ml of VWF: Ag, 50-90 U/ml of VWF: CB and VWF: RCo (i.e. CB/Ag ratio around 0.6-0.9 and RCo/Ag ratio around 0.6-1.1). Study-determined FVIII: C and VWF: RCo levels were similar to manufacturer-assigned levels. The LMW multimer band seen with AHF HP was also observed with Humate/Haemate. All three lots of Biostate contained in the vicinity of 40-55 U/ml of FVIII:C, 105-170 U/ml of VWF:Ag, 90-150 U/ml of VWF:CB, and 90-135 U/ml of VWF:RCo (i.e. CB/Ag and RCo/Ag ratios around 0.7-1.0). Study-determined FVIII:C levels were similar to manufacturer-assigned levels. The LMW multimer band seen with AHF HP was not observed with Biostate. The defined pattern of increasing CB/ Ag from AHF HP to Humate/Haemate and Biostate was consistently observed in study data from each of the five laboratories. In conclusion, study findings indicate some differences in the retention of functional/ HMW VWF between factor concentrates, and this is expected to have significant implications in terms of clinical efficacy for therapy in VWD.