An Assessment of the Human Subjects Protection Review Process for Exempt Research.

Medical and public health research includes surveys, interviews, and biospecimens - techniques that do not present substantial risks to subjects. Consequently, this research is exempt from regulation under the Federal Common Rule. Nevertheless, at many institutions, exempt research is frequently subject to the same regulatory process that is required for non-exempt research, requiring the consumption of time and resources for review by Institutional Review Board members or staff. The federal government has indicated an intention to reform and centralize this system, but has not yet specified the form that it will use instead. By examining the policies of the top 50 research institutions, this article assesses institutional practices surrounding exempt research, quantifies the extent of exempt-research review requirements, documents a problem of "over-compliance," and makes recommendations for reform.

Reduced Myxobolus cerebralis actinospore production in a Colorado reservoir may be linked to changes in Tubifex tubifex population structure.

Elucidating the dynamics of a parasitic infection requiring two hosts in a natural ecosystem can be a daunting task. Myxobolus cerebralis (Mc), the myxozoan parasite that causes whirling disease in some salmonids, was detected in the Colorado River upstream of Windy Gap Reservoir (WGR) in 1988. Subsequently, whirling disease was implicated in the decline of wild Rainbow Trout Oncorhynchus mykiss in the river when WGR was identified as a point source of Mc triactinomyxons (TAMs). Between 1997 and 2004, numerous investigations began to elucidate the etiology of Mc in WGR. During this period, Mc TAM production in WGR declined more than 90%. Explanations for the decline have included differences in stream discharge between years, changes in the thermal regime of the lake, severe drought, changes in the fish population structure in WGR, and reductions in the prevalence and severity of Mc infection in salmonids in the Colorado and Fraser rivers upstream of WGR. All of these have been discredited as explanations for the reduced TAM production. In 2005, a new study was conducted to replicate the studies completed in 1998. In this paper, the results of a new real-time polymerase chain reaction assay utilized to quantify the mitochondrial 16S rDNA specific to each of four lineages of Tubifex tubifex in pooled samples of 50 oligochaetes are presented. These results suggest that compared with 1998, the densities of aquatic oligochaetes and T. tubifex have increased, TAM production has been greatly reduced, and the decline is congruent with the dominance of lineages I, V, and VI of T. tubifex-three lineages that are refractory or highly resistant to Mc infection-in the oligochaete population. While it is possible that the resistant lineages function as biofilters that deactivate Mc myxospores, the reason for the decline in TAM production in WGR remains an enigma.

Inhibition of the A-type K+ channels of dorsal root ganglion neurons by the long-duration anesthetic butamben.

n-Butyl-p-aminobenzoate (BAB; butamben) is a long-duration anesthetic used for the treatment of chronic pain. Epidural administration of BAB is thought to reduce the electrical excitability of dorsal root nociceptor fibers by inhibiting voltage-gated ion channels. To further investigate this mechanism, we examined the effects of BAB on the potassium currents of acutely dissociated neurons from the rat dorsal root ganglion (DRG). These neurons express a rapidly inactivating A-type K(+) current (I(A)) that is resistant to tetraethylammonium (20 mM) but inhibited by 4-aminopyridine (5 mM). At low concentrations, BAB (< or =1 microM) selectively inhibited the I(A) component of DRG K(+) current. The voltage dependence of activation and inactivation, kinetics of recovery from inactivation, and the pharmacology of the DRG I(A) were similar to those of the Kv4 family of K(+) channels. Reverse transcription-polymerase chain reaction was used to establish that the messages encoding for all three of the mammalian Kv4 channel subunits (Kv4.1-Kv4.3) were present in the rat DRG. BAB produced a high-affinity, partial inhibition of heterologously expressed Kv4.2 channels (K(D) = 59 nM) but did not alter the kinetics or voltage sensitivity of gating. Substituting polar threonines for conserved hydrophobic residues of the S6 segment weakened BAB binding but did not alter the voltage-dependent gating of the Kv4.2 channel. At physiological pH, BAB is uncharged, suggesting that hydrophobic interactions may contribute to drug binding. The data support a mechanism in which BAB binds near the narrow cytoplasmic entrance of Kv4 channels and inhibits current by a pore blocking mechanism.

Healthcare and the information revolution: re-configuring the healthcare service encounter.

Utilisation of internet-derived information by patients within the healthcare service encounter is increasing. Encompassing both the use of unidirectional information sites as well as bidirectional computer-mediated communities, this is manifest in the growth of consumerist expectations on the part of patients. Based on interviews with patients, professionals and internet site managers, this paper examines the role of the internet as a source of patient information and support, and in particular the effect on the relationship between 'informed' consumers and professionals involved in the delivery of healthcare services. The core challenge for informed consumers is to develop frameworks that facilitate robust dialogue, exchange of information and emotional support to complement their rising authority. The parallel challenge is for the established medical profession to recognize the consequences of this evolving dialogue and develop approaches to service delivery that effectively engage with consumers on the basis of this increasing authority.

Characteristics of rheumatoid arthritis patients: who participates in long-term research and who drops out?

OBJECTIVE: A 10-year study of rheumatoid arthritis (RA) patients was conducted to identify characteristics associated with continued participation in a long-term research project. METHODS: Nine hundred eighty-eight RA patients were recruited from 56 private rheumatology practices. Over the course of the study, 45 patients died and were eliminated from the analysis. Patients were interviewed by phone each year for 10 years, and their physicians provided clinical data. Variables measured included demographic characteristics, perceived health status, employment status, family responsibilities, social support, and clinical health status. RESULTS: Forty-six percent of patients remained in the study after 10 years. Survival analysis using Cox regression techniques assessed baseline factors that significantly predicted characteristics of patients who remained in the study. The multivariate analysis found that more educated patients, female patients, those with moderate to high levels of social support, patients having fewer joint groups with flares, and employed patients were more likely to remain in the study. Disease characteristics of stage of disease, level of pain, self-reported level of physical disability, and duration of RA were not significantly associated with continued study participation. CONCLUSION: The results suggest that psychosocial and socioeconomic factors are more important determinants of continued participation in long-term research studies than are most clinical disease characteristics. Among clinical variables, only the active disease characteristic of joint flares predicted continued study participation. Overall disease characteristics such as disease stage or duration did not predict subject attrition.

Marital satisfaction in couples with rheumatoid arthritis.

OBJECTIVE: To understand correlates of marital satisfaction in persons with rheumatoid arthritis (RA) and their spouses. METHODS: In a cross-sectional survey, 79 persons with RA and 78 spouses completed the Kansas Marital Satisfaction Scale, the revised Ways of Coping Questionnaire scales, and the Health Assessment Questionnaire. A series of linear regression analyses were then performed to investigate correlates of marital satisfaction for patients and spouses. RESULTS: Seventy-six percent of patients were women. Mean patient age was 56.5 years (+/- 12.5 years), number of years married was 30.7 (+/- 13.5), and duration of RA was 14.2 years (+/- 9.0 years). Demographic features of spouses resembled those of patients. Patients and spouses were generally satisfied with their marriages. Linear regression analyses showed that lower marital satisfaction in patients was associated with higher education level (P < 0.01), patient's greater use of escape into fantasy (P < 0.01), patient's greater use of finding blame (P < 0.05), and spouse's higher use of escape into fantasy (P < 0.001). Spouses less satisfied with their marriages were more likely to use passive acceptance (P < 0.05) and less likely to find blame (P < 0.05). Female spouses were less likely to be satisfied in their marriages (P < 0.01) than male spouses. CONCLUSIONS: This study indicates that certain passive coping styles are associated with lower marital satisfaction in persons with RA and their spouses. More highly educated patients and female spouses are also less satisfied in their marriages. These cross-sectional correlations should not be regarded as causal and should be examined further in longitudinal studies.

Employment patterns and their effect on health outcomes among women with rheumatoid arthritis followed for 7 years.

OBJECTIVE: To evaluate the effect of employment on health outcomes in a sample of women with rheumatoid arthritis (RA) and to test the hypothesis that employment confers a health benefit to women. METHODS: Seven hundred sixty women with a diagnosis of RA were recruited from a national random sample of private rheumatology practices in 1988, and 416 remained in the study after 7 years of followup in 1994. Women were interviewed each year by telephone to collect data on demographic variables, health status, and employment status. Clinical data were provided by referring physicians. RESULTS: Most women (175, 42%) were not employed outside the home 1988-94, although 96 of those women (23% of the sample) had been employed previously. Twenty-seven percent (n = 112) were employed all 7 years and 31% (n = 129) had been employed between one and 6 years. Women who were employed had significantly better health outcomes measured by pain, disability, role functioning, and clinical status compared to those who were never employed and those who had been employed before the study. Women who were previously employed, but not employed during the study period experienced the worst health outcomes. This difference in health status, however, appeared before entry into this study. CONCLUSION: Employed women with RA had better health status than women who were not employed outside the home. Previously employed women had worse health outcomes than both working women and women who were never employed, suggesting that loss of employment is associated with worse health. Further research is needed to investigate underlying factors contributing to worse health status among unemployed women and to better health among employed women.

Gene mapping from a bovine 1;29 DNA library prepared with chromosome microdissection.

Bovine gene mapping is progressing rapidly using syntenic group mapping based on somatic cell hybrids and linkage, and to a lesser extent on in situ hybridization. Single chromosome DNA libraries are a logical next step, and this was, therefore, the aim of our laboratory. Since we have access to several cattle with t(1;29) and this chromosome is readily distinguishable, we chose this as our first target--recognizing that we would not produce a "single" chromosome library in the strict sense because two autosomes are represented. We utilized an inverted microscope and a micromanipulator fitted with glass instruments pulled specifically to dissect off approximately 100 t(1;29) chromosomes per microdrop. A glass chamber made to accommodate a hanging drop was used to extract the DNA under a dissecting microscope. The DNA was then cleaved with EcoRI and inserted in lambda gtwes arms. Host cells were then infected with these phage and positive clones obtained. The first clone, isolated from this library by hybridization with a human collagen 6A1 cDNA, was mapped by in situ hybridization to bovine Chromosome some (Chr) 1q12-q14, near the centromere. The second clone, an anonymous DNA fragment (D1S11), was mapped to 1q43-q46, near the terminal end.

RFLPs for somatotropic genes identify quantitative trait loci for growth in mice.

Restriction fragment length polymorphisms for somatotropic genes were tested for associations with body weight and postweaning growth rate in mice. Polymorphisms for growth hormone (GH) and insulin-like growth factor 2 (IGF-2) genes were identified in stock population lines which had been subjected to long-term selection for high 42-day body weight (H lines) or randomly mated (FP and C lines). Two F2 populations of mice (5F2 and MF2) were generated from crosses between a single H line of mice and two unselected control lines and subsequently, two divergently weight selected sublines were generated from each F2 population. The GHh allele which had originally been fixed in three of four H lines and absent from all FP and C lines was found to have a significant (P less than 0.01) effect on 42-day weight and postweaning growth rate in the F2 populations. However, GHh was associated with lower 42-day weight in the F2 populations, suggesting that the positive association between GHh and weight in the stock population was unique to the high weight selected genetic background of those lines. In agreement with this, the frequency of GHh increased in sublines selected for high 42-day weight and decreased in sublines selected for low 42-day weight. The IGF-2H5 allele was associated with higher weights in a sex-dependent manner in 5F2. In the high selected subline derived from 5F2, a significant increase in the frequency of IGF-2H5 was observed. Therefore this allele, in contrast to GHh, appears to be a positive indicator of growth irrespective of genetic background.

The geometry of the adult canine proximal femur.

The canine is often used as a model to study functional bone adaptation after total hip replacement. To improve our understanding of the model, we defined the central tendencies and statistical variations in the cross-sectional geometry, angle of anteversion, and cervicodiaphyseal angle of the proximal femur in 15 adult male mongrel dogs and compared the results with published reports of the human femur. Numerous similarities in the cross-sectional geometry of the canine and the human femur were noted, supporting the use of the canine as a model. The two species differed in that the orientation of the principal axes in the proximal cross sections was not related to the angle of anteversion in the canine femur, whereas these angles are related in humans. In addition, the canine medullary canal is larger than the human medullary canal relative to the external dimensions of the femur, and hence the canine has relatively thinner cortical bone. This difference in femoral cross-sectional geometry may explain, in part, why the canine provides an accentuated model of bone loss in hip arthroplasty experiments.