Neuro-QOL: brief measures of health-related quality of life for clinical research in neurology.

OBJECTIVE: To address the need for brief, reliable, valid, and standardized quality of life (QOL) assessment applicable across neurologic conditions. METHODS: Drawing from larger calibrated item banks, we developed short measures (8-9 items each) of 13 different QOL domains across physical, mental, and social health and evaluated their validity and reliability. Three samples were utilized during short form development: general population (Internet-based, n = 2,113); clinical panel (Internet-based, n = 553); and clinical outpatient (clinic-based, n = 581). All short forms are expressed as T scores with a mean of 50 and SD of 10. RESULTS: Internal consistency (Cronbach α) of the 13 short forms ranged from 0.85 to 0.97. Correlations between short form and full-length item bank scores ranged from 0.88 to 0.99 (0.82-0.96 after removing common items from banks). Online respondents were asked whether they had any of 19 different chronic health conditions, and whether or not those reported conditions interfered with ability to function normally. All short forms, across physical, mental, and social health, were able to separate people who reported no health condition from those who reported 1-2 or 3 or more. In addition, scores on all 13 domains were worse for people who acknowledged being limited by the health conditions they reported, compared to those who reported conditions but were not limited by them. CONCLUSION: These 13 brief measures of self-reported QOL are reliable and show preliminary evidence of concurrent validity inasmuch as they differentiate people based upon number of reported health conditions and whether those reported conditions impede normal function.

Membrane actions of vitamin D metabolites 1alpha,25(OH)2D3 and 24R,25(OH)2D3 are retained in growth plate cartilage cells from vitamin D receptor knockout mice.

1alpha,25(OH)(2)D(3) regulates rat growth plate chondrocytes via nuclear vitamin D receptor (1,25-nVDR) and membrane VDR (1,25-mVDR) mechanisms. To assess the relationship between the receptors, we examined the membrane response to 1alpha,25(OH)(2)D(3) in costochondral cartilage cells from wild type VDR(+/+) and VDR(-/-) mice, the latter lacking the 1,25-nVDR and exhibiting type II rickets and alopecia. Methods were developed for isolation and culture of cells from the resting zone (RC) and growth zone (GC, prehypertrophic and upper hypertrophic zones) of the costochondral cartilages from wild type and homozygous knockout mice. 1alpha,25(OH)(2)D(3) had no effect on [(3)H]-thymidine incorporation in VDR(-/-) GC cells, but it increased [(3)H]-thymidine incorporation in VDR(+/+) cells. Proteoglycan production was increased in cultures of both VDR(-/-) and VDR(+/+) cells, based on [(35)S]-sulfate incorporation. These effects were partially blocked by chelerythrine, which is a specific inhibitor of protein kinase C (PKC), indicating that PKC-signaling was involved. 1alpha,25(OH)(2)D(3) caused a 10-fold increase in PKC specific activity in VDR(-/-), and VDR(+/+) GC cells as early as 1 min, supporting this hypothesis. In contrast, 1alpha,25(OH)(2)D(3) had no effect on PKC activity in RC cells isolated from VDR(-/-) or VDR(+/+) mice and neither 1beta,25(OH)(2)D(3) nor 24R,25(OH)(2)D(3) affected PKC in GC cells from these mice. Phospholipase C (PLC) activity was also increased within 1 min in GC chondrocyte cultures treated with 1alpha,25(OH)(2)D(3). As noted previously for rat growth plate chondrocytes, 1alpha,25(OH)(2)D(3) mediated its increases in PKC and PLC activities in the VDR(-/-) GC cells through activation of phospholipase A(2) (PLA(2)). These responses to 1alpha,25(OH)(2)D(3) were blocked by antibodies to 1,25-MARRS, which is a [(3)H]-1,25(OH)(2)D(3) binding protein identified in chick enterocytes. 24R,25(OH)(2)D(3) regulated PKC in VDR(-/-) and VDR(+/+) RC cells. Wild type RC cells responded to 24R,25(OH)(2)D(3) with an increase in PKC, whereas treatment of RC cells from mice lacking a functional 1,25-nVDR caused a time-dependent decrease in PKC between 6 and 9 min. 24R,25(OH)(2)D(3) dependent PKC was mediated by phospholipase D, but not by PLC, as noted previously for rat RC cells treated with 24R,25(OH)(2)D(3). These results provide definitive evidence that there are two distinct receptors to 1alpha,25(OH)(2)D(3). 1alpha,25(OH)(2)D(3)-dependent regulation of DNA synthesis in GC cells requires the 1,25-nVDR, although other physiological responses to the vitamin D metabolite, such as proteoglycan sulfation, involve regulation via the 1,25-mVDR.

The effect of arbitration program characteristics on applicants' intentions toward potential employers.

The authors examined intentions toward prospective employers with different alternative dispute resolution (ADR) policies and no ADR policy. In Study 1, students (N = 124) were randomly assigned to 1 of 4 conditions in which 2 variables, arbitration policy presence or absence and firm desirability, were manipulated. The presence of a voluntary, nonbinding arbitration policy had no impact on intentions and did not interact with firm desirability. In Study 2, students (N = 273) were randomly assigned to 1 of 8 conditions (mandatory vs. voluntary arbitration, binding vs. nonbinding arbitration, and highly desirable vs. less desirable employer). Both mandatory and binding arbitration policies were related to less favorable intentions toward firms. Predictions regarding the interaction of ADR policy and firm desirability were partially supported. Some support was found for the interaction between ADR policy and ethnicity.

Nursing assessment of adult females who are alcohol dependent and victims of sexual abuse.

Women who develop alcohol dependence pose a serious health threat to themselves, their families, and their communities. One of the factors theorized to be a major influence in the development of maladaptive behaviors relative to alcohol use in women is childhood sexual abuse. This paper uses King's theory of dynamic interacting systems to examine relationships between the personal, family, and community variables that may influence women who have been victims of childhood sexual abuse and develop alcohol dependence. Guidelines for a research-based nursing assessment are suggested.

Using follow-up support with grand rounds CME in community hospitals.

PURPOSE: To determine the proportion of regional primary care physicians who would attend grand rounds on preventive services and their interest in and use of free follow-up enabling and reinforcing assistance to implement changes in their practice routines. METHOD: From January to July 1992 grand rounds on early detection of cancer were offered by Dartmouth Medical School at 38 acute care community hospitals in New Hampshire and Vermont. The target audience of 679 family physicians and general internists was identified through state medical society and hospital attending lists. The hour-long grand rounds program described preventive service guidelines and an office system that promoted their implementation. Follow-up practice support with planning, office staff training, and materials were offered to augment the effects of the grand rounds. Attendance was determined by sign-in documents. In addition, all attendees were asked to complete a survey regarding practice and personal characteristics and interest in follow-up assistance. Statistical comparisons were made using chi square and Fisher's exact tests. RESULTS: In all, 261 family medicine physicians and general internists (38.4%) attended. Certain categories of physicians were more likely to have attended: internists, those younger than 55 years, and physicians on the staffs of hospitals located in small towns. Assistance was requested by 70.1% of the attendees; many requested more than one type of assistance. Physicians from hospitals in smaller towns were more likely to show interest in follow-up assistance and use it when offered. CONCLUSION: Many of the grand rounds attendees were receptive to follow-up assistance that could improve the preventive services they provided. Most hospitals offer grand rounds, and many organizations have interest in and resources for helping physicians provide high-quality care. Future research should establish the best linkage to the actual care provided in practices and explore the relevance of similar approaches to clinical areas beyond prevention.

Physician preventive care philosophy and the five year durability of a preventive services office system.

A group of 30 community physicians who practiced in northeastern United States and who participated in the Cancer Prevention in Community Practice project in 1988 were interviewed five years later. The aim of the interviews was to assess the long-term impact of the preventive services office system which had been introduced by the project. The qualitative analysis of interviews revealed three distinct physician philosophies about the provision of preventive services: a Request Only focus, responding to specific patient inquiries about prevention but taking no initiative to recommend indicated services; a Health Maintenance Visit focus, providing indicated services only during visits specifically scheduled for preventive care; and an Opportunistic Prevention focus, providing indicated preventive services at every chance. Physicians demonstrated these philosophies in their overall view of disease prevention, perceived obstacles to delivery of preventive care, as well as in their continued use of flow sheets and their impression of the value of the Cancer Prevention in Community Practice project. The long-term impact of the office system was the most apparent in the Opportunistic Prevention group. We conclude that the durability of a preventive services office system is influenced by a physician's preventive care philosophy.

Virologic markers of human immunodeficiency virus type 1 in cerebrospinal fluid of infected children.

To identify virologic correlates associated with central nervous system (CNS) abnormalities in children infected with human immunodeficiency virus type 1 (HIV-1), cerebrospinal fluid (CSF) was examined for virologic markers and correlated with neurodevelopmental status and neuroimaging abnormalities. Of 30 children, 18 (60%) had at least 1 culture-positive CSF sample; in total, 21 (55%) of 38 CSF specimens were culture-positive. CSF white blood cell counts were higher in specimens that were culture-positive (P = .01). HIV-1 RNA was detected in 90% of CSF samples, and RNA levels > or = 10,000 copies/mL were found in 6 (75%) of 8 children with severe neurocognitive impairment (P = .08) and 11 (73%) of 15 children with a cognitive index < or = 85 (P = .04). Higher RNA levels were associated with abnormal brain imaging scans (P = .04) and with neurocognitive deficits (P = .04). Thus, HIV-1 is present within the CNS of most infected children, and neurocognitive impairment appears to be associated with increased HIV-1 replication.

Virologic characterization of primary human immunodeficiency virus type 1 infection in a health care worker following needlestick injury.

A health care worker (HCW) was infected via needlestick with human immunodeficiency virus (HIV) type 1 from a subject with AIDS who harbored a zidovudine-resistant, syncytium-inducing (SI) HIV strain. The phenotypic characteristics of the HIV-1 isolates obtained from the HCW and markers of virus load were followed for 20 months. Although the HCW was initially infected with an SI strain, within 75 days of infection the isolate became non-SI and remained so for > or = 635 days. Even though the AIDS patient had a zidovudine-resistant virus, the HCW was infected with a zidovudine-sensitive virus. Plasma RNA levels peaked 20 days after infection, declined rapidly within 2 weeks, and remained stable for the duration of follow-up. Similarly, the HCW's CD4 lymphocyte count remained stable throughout the study. Thus, selection for non-SI and zidovudine-sensitive virus occurred in the HCW, who, after initial symptomatic infection associated with high levels of plasma HIV-1 RNA, developed low plasma RNA copy numbers and stable CD4 lymphocyte counts.

Viral measurement by polymerase chain reaction-based assays in human immunodeficiency virus-infected infants.

Serial samples from human immunodeficiency virus-infected infants in the first year of life were analyzed by quantitative human immunodeficiency virus polymerase chain reaction assays. Very high, persistent levels of plasma RNA and proviral DNA were detected throughout the study period, suggesting the absence of an effective immune response. Most patients had normal CD4 lymphocyte counts and were symptom free for the first 3 to 6 months despite high levels of viral replication. These findings support the evaluation of early intervention (before symptoms develop) and efforts to establish the predictive value of these assays.

Rapid and simple PCR assay for quantitation of human immunodeficiency virus type 1 RNA in plasma: application to acute retroviral infection.

A method for quantitating human immunodeficiency virus type 1 plasma viremia may be useful in monitoring disease progression and the responsiveness of patients to a therapeutic regimen or vaccine. A quantitative assay for viral RNA in plasma or sera that differs in several aspects from those reported previously was developed. First, whereas conventional reverse transcriptase-PCR assays involve a two-step process and use two enzymes, the method described uses a single enzyme, rTth DNA polymerase, for both reverse transcription and PCR. The reactions are carried out in a single tube and with a single buffer solution with uninterrupted thermal cycling. Second, uracil-N-glycosylase and dUTP are incorporated into the reaction mixtures to ensure that any carryover of DNA from previous amplifications will not compromise quantitation. Third, a quantitation standard is incorporated into each reaction mixture so that differences in amplification efficiency caused by sample interferents, variability in reaction conditions, or thermal cycling can be normalized. To ensure comparable amplification efficiency, the quantitation standard has the same primer-binding regions as the human immunodeficiency virus type 1 target and generates an amplified product of the same size and base composition. The probe-binding region was replaced with a sequence that can be detected separately. Fourth, a colorimetric detection format was modified to provide at least a four-log-unit dynamic range. The quantitative assay requires only a single amplification of the sample and can be completed in less than 8 h. The procedure was used on archival samples to demonstrate the viremic spike in acute infection and the suppressed levels of circulating virus following seroconversion.

Low incidence of HTLV infections in random blood donors with indeterminate western blot patterns.

Peripheral blood mononuclear cells (PBMCs) were recovered from platelet units of 61 blood donors who were HTLV-I positive and 3 blood donors who were HTLV-I negative on enzyme-linked immunosorbent assay (ELISA). Western blot analyses were performed on the sera and DNA was prepared from the PBMCs and analyzed by the polymerase chain reaction (PCR). Of the 61 repeatably reactive samples, 2 were positive, 26 were negative, and 33 were interpreted as indeterminate on Western blot. HTLV-II sequences were detected by PCR in one of the Western blot-positive samples, as well as in one Western blot-indeterminate sample that showed reactivity to p24 only. HTLV-I sequences were detected in the second Western blot-positive sample. HTLV sequences were not detected in the remaining samples, which suggested that the majority of individuals with indeterminate results on Western blots that used one set of commercially available reagents are not infected with HTLV. It is demonstrated in this study that PCR can be used not only to resolve the infection status of individuals with indeterminate Western blots but also to distinguish between HTLV-I and HTLV-II.

High prevalence of HTLV-II among intravenous drug abusers: PCR confirmation and typing.

The polymerase chain reaction (PCR) was used to confirm the presence of human T-cell lymphotropic viruses (HTLV) in intravenous drug users (IVDU) whose sera were reactive by immunofluorescence assay (IFA) for HTLV-1/-II antibody. Peripheral blood mononuclear cells from 41 IFA-positive and 19 IFA-negative individuals were analyzed. HTLV sequences were detected in 39/41 IFA-positive samples; 36 were HTLV-II positive and 3 were HTLV-I positive. Two IFA antibody-positives were negative by both PCR and by enzyme immunoassay (EIA). One IFA and EIA antibody-negative sample was positive for HTLV-II by PCR. This study indicates a high prevalence of HTLV-II among IVDUs and further demonstrates the feasibility of using PCR to differentiate between HTLV-I and -II.

Effects of primer-template mismatches on the polymerase chain reaction: human immunodeficiency virus type 1 model studies.

We investigated the effects of various primer-template mismatches on DNA amplification of an HIV-1 gag region by the polymerase chain reaction (PCR). Single internal mismatches had no significant effect on PCR product yield while those at the 3'-terminal base had varied effects. A:G, G:A, and C:C mismatches reduced overall PCR product yield about 100-fold, A:A mismatches about 20-fold. All other 3'-terminal mismatches were efficiently amplified, although the G:G mismatches appeared to be more sensitive to sequence context and dNTP concentrations than other mismatches. It should be noted that mismatches of T with either G, C, or T had a minimal effect on PCR product yield. Double mismatches within the last four bases of a primer-template duplex where one of the mismatches is at the 3' terminal nucleotide, in general, reduced PCR product yield dramatically. The presence of a mismatched T at the 3'-terminus, however, allowed significant amplification even when coupled with an adjacent mismatch. Furthermore, even two mismatched Ts at the 3'-terminus allowed efficient amplification.