An RNA pseudoknot stimulates HTLV-1 pro-pol programmed -1 ribosomal frameshifting.

Programmed -1 ribosomal frameshifts (-1 PRFs) are commonly used by viruses to regulate their enzymatic and structural protein levels. Human T-cell leukemia virus type 1 (HTLV-1) is a carcinogenic retrovirus that uses two independent -1 PRFs to express viral enzymes critical to establishing new HTLV-1 infections. How the cis-acting RNA elements in this viral transcript function to induce frameshifting is unknown. The objective of this work was to conclusively define the 3' boundary of and the RNA elements within the HTLV-1 pro-pol frameshift site. We hypothesized that the frameshift site structure was a pseudoknot and that its 3' boundary would be defined by the pseudoknot's 3' end. To test these hypotheses, the in vitro frameshift efficiencies of three HTLV-1 pro-pol frameshift sites with different 3' boundaries were quantified. The results indicated that nucleotides included in the longest construct were essential to highly efficient frameshift stimulation. Interestingly, only this construct could form the putative frameshift site pseudoknot. Next, the secondary structure of this frameshift site was determined. The dominant structure was an H-type pseudoknot which, together with the slippery sequence, stimulated frameshifting to 19.4(±0.3)%. The pseudoknot's critical role in frameshift stimulation was directly revealed by examining the impact of structural changes on HTLV-1 pro-pol -1 PRF. As predicted, mutations that occluded pseudoknot formation drastically reduced the frameshift efficiency. These results are significant because they demonstrate that a pseudoknot is important to HTLV-1 pro-pol -1 PRF and define the frameshift site's 3' boundary.

Bioaccumulation of trace metals in shellfish and fish of Bonny River and creeks around Okrika in Rivers State, Nigeria.

Lead, nickel, vanadium and cadmium were determined in fish and shellfish muscles, to assess contamination levels and identify bio-indicators. Vanadium was not detectable. Lead and cadmium were slightly above legal limits used in South East Asia, but lower than those of Australia and New Zealand. Higher contents of nickel, cadmium and lead in Pachymelania aurita and Crassostrea rhizophorae, lead in Mugil cephalus and cadmium in Periophthalmus koelreuteri, mark these species out as possible bio-indicators for the three metals in aquatic systems. Patterns of bioaccumulation seem to suggest that biophysiological and ecological characteristics influence bioaccumulation of trace metals in fish and shell fish.

A randomized trial of a brief intervention to increase fruit and vegetable intake: a replication study among callers to the CIS.

BACKGROUND: Results are reported from a large randomized trial designed to increase fruit and vegetable consumption among callers to the National Cancer Institute's Cancer Information Service (CIS) (n = 1,717). METHODS: CIS callers assigned to the intervention group (n = 861) received a brief proactive educational intervention over the telephone at the end of usual service, with two follow-up mailouts. Key educational messages and print material derived from the NCI 5 A Day for Better Health program were provided to intervention participants. Participants were interviewed by telephone at 4 weeks (n = 1,307), 4 months (n = 1,180), and 12 months for follow-up (n = 1,016). RESULTS: Results obtained from a single-item measure of fruit and vegetable consumption indicate a significant intervention effect of 0.88 servings per day at 4 weeks follow-up (P < 0.001), 0.63 servings per day at 4 months follow-up (P < 0.001), and 0.43 servings per day at 12 months follow-up (P < 0.001). Using a 7-item food frequency measure, an intervention effect of 0.63 servings per day was obtained at 4 weeks follow-up (P < 0.001), compared with 0.39 servings per day at 4 months follow-up (P = 0.002) and 0.44 servings per day at 12 months follow-up (P = 0.002). A 24-h recall assessment included in the 4-month interviews also yielded a significant intervention effect of 0.67 servings per day (P = 0.015). The vast majority of callers (90%) endorsed the strategy of providing 5 A Day information proactively within the CIS. CONCLUSIONS: This brief educational intervention was associated with higher levels of self-reported fruit and vegetable intake at both short- and long-term follow-up. Additional research is recommended to test this or a similar intervention in diverse populations.

Smoking cessation interventions among hospitalized patients: what have we learned?

BACKGROUND: We conducted a structured review of controlled studies on inpatient hospital-based smoking cessation interventions. METHODS: Electronic searches were conducted with two different search engines, and reference sections of articles located were also reviewed. The RE-AIM framework was used to organize the review around the issues of reach, efficacy, adoption, implementation, and maintenance of interventions. RESULTS: Thirty-one intervention articles were located, 20 of which included a comparison condition and were included in the review. Overall, a moderate number of studies (13/20) reported on reach, which was highly variable and limited (30-50% in most studies), while few reported on implementation (7/20). Longer term cessation results produced relative risk ratios of 0.9-2.3, with a median of 1.5. Increases in quit rates above the control condition ranged from -1 to 10% (median 4%) among general admission patients and from 7 to 36% (median 15%) among cardiac admission patients. Studies with a dedicated smoking cessation counselor and 3-5 months of relapse prevention had a significant impact on cessation rates. Study settings (adoption) were limited to university, Veterans affairs, and HMO hospitals. Maintenance at the individual level was variable and related to the presence of a relatively intensive initial intervention and a sustained relapse prevention intervention. CONCLUSIONS: Efficacious inpatient smoking programs have been developed and validated. The challenge now is to translate these interventions more widely into practice, given changing hospitalization patterns.

Motor neuron diseases in the University Hospital of Fortaleza (Northeastern Brazil): a clinico-demographic analysis of 87 cases

In this retrospective (1980-1998) study, we have analyzed clinico-demographically, from the records of the University Hospital of Fortaleza (Brazil), a group of 87 patients showing signs and symptoms of motor neuron diseases (MNDs). Their diagnosis was determined clinically and laboratorially. The WFN criteria were used for amyotrophic lateral sclerosis (ALS) diagnosis. The clinico-demographic analysis of the 87 cases of MNDs showed that 4 were diagnosed as spinal muscular atrophy (SMA), 5 cases as ALS subsets: 2 as progressive bulbar paralysis (PBP), 2 as progressive muscular atrophy (PMA) and 1 as monomelic amyotrophy (MA), and 78 cases of ALS. The latter comprised 51 males and 27 females, with a mean age of 42.02 years. They were sub-divided into 4 groups according to age: from 15 to 29 years (n= 17), 30 to 39 years (n= 18), 40 to 69 years (n= 39) and 70 to 78 years (n= 4). From the 78 ALS patients, 76 were of the classic sporadic form whilst only 2 were of the familial form. The analysis of the 87 patients with MNDs from the University Hospital of Fortaleza showed a predominance of ALS patients, with a high number of cases of juvenile and early onset adult sporadic ALS

Physician perspectives on increasing minorities in cancer clinical trials: an Eastern Cooperative Oncology Group (ECOG) Initiative.

PURPOSE: This paper describes the ECOG-NMA Minority Accrual Initiative to assure minority participation in cancer clinical trials. METHODS: Focus groups were held to identify physician-reported barriers to the enrollment of minority patients in Cleveland, OH, Indianapolis, IN, Santa Clara County, CA, and Philadelphia, PA. Community physicians affiliated with the National Medical Association (NMA), and Eastern Cooperative Oncology Group (ECOG) investigators participated in the focus groups. A four-step process consisting of focus group workshops were conducted to (i) identify barriers, (ii) develop potential solutions to the barriers, (iii) define solutions to barriers involving specific clinical trials, and (iv) implement the solutions. RESULTS: Focus group participants identified physician lack of information, patient fears and suspicion, the fear of losing patients, and distrust of the health care system as the major barriers to enrollment of African Americans. We found significant differences between community physicians and cancer program physicians in several areas. Community physicians emphasized personal contacts to address the lack of information and to overcome patient fears and suspicions, while the cancer program physicians emphasized printed materials. There was no difference by region in the barriers identified in the focus group workshops; however, the proposed solutions to overcoming the barriers were specific to each site. CONCLUSION: The four-step process developed by the ECOG and the NMA used the focus group methodology to identify and overcome barriers to participation of African Americans in cancer clinical trials. Outreach efforts to educate patients, their families, and community physicians about cancer clinical trials should be directed at overcoming patient suspicions and providing practical information to physicians about specific trials and how to enroll patients.

Age-related differences in the quality of life of breast carcinoma patients after treatment.

BACKGROUND: The objective of this study was to compare the quality of life (QOL) of younger (< or =50 years) versus older (>50 years) women on recent completion of treatment of breast carcinoma. METHODS: Data reported herein were obtained from a baseline assessment of 304 breast carcinoma patients. These patients were enrolled in a multiinstitutional, randomized trial testing a psychosocial telephone counseling intervention for breast carcinoma patients immediately after treatment. The assessment was made using a self-administered (mail) questionnaire, with an overall response rate of 86%. Included in this questionnaire were standardized measures of QOL using the Functional Assessment of Cancer Therapy-Breast instrument, the Center for Epidemiologic Studies Depression Scale, and the Impact of Event Scale. RESULTS: Comparisons of baseline data analyzed according to age approximating menopausal status (< or =50 years and >50 years) indicated that younger women reported significantly greater QOL disturbance. QOL was significantly worse for younger women globally (P = 0.021), and with regard to domains of emotional well-being (P = 0.0002) and breast carcinoma specific concerns (P = 0.022). Furthermore, symptoms of depression (P = 0.041) and disease specific intrusive thoughts (P = 0.013) were significantly worse for younger women. No significant sexual dysfunction or body image differences were noted. CONCLUSIONS: Results from this analysis suggest that younger women with breast carcinoma should be considered to be at high risk for QOL disruption and significant clinical distress. Targeted interventions for this cohort are recommended.

The effect of baclofen on spontaneous and evoked behavioral expression of experimental neuropathic chronic pain

Baclofen (Beta-p-chlorophenyl-GABA) has been used in humans to treat spasticity, as well as trigeminal neuralgia Since GABA (gamma-aminobutyric acid) has been implicated in inhibitory and analgesic effects in the nervous system, it was of interest to study the effect of baclofen in experimental neuropathic pain. With this purpose, experiments were carried out in 17 neuropathic rats with constrictive sciatic injury, as described by Bennet and Xie (1988), taking as pain parameters scratching behaviour and the latency to the thermal nociceptive stimulus. The results showed that baclofen induces, in a dose-dependent manner, significant decrease (p<0.05) of scratching behaviour and significant increase (p<0.05) of the latency to the nociceptive thermal stimulus. The absence of antagonism of naloxone suggested a non-participation of an opioid-mediated mechanism in this analgesic effect of baclofen on experimental neuropathic pain.

Recruiting minority cancer patients into cancer clinical trials: a pilot project involving the Eastern Cooperative Oncology Group and the National Medical Association.

PURPOSE: Minority accrual onto clinical trials is of significant interest to cooperative oncology study groups. The Eastern Cooperative Oncology Group (ECOG) conducted a study to identify barriers and solutions to African American accrual onto clinical trials. METHODS: We hypothesize that the National Medical Association (NMA) might provide insight into ways to increase minority participation and that ECOG might facilitate that participation. Four sites were selected in which NMA chapters existed and ECOG main institutions with less than half of the corresponding percentage of minorities in their communities entered trials for 1992. Fifteen workshops were conducted using discussions and open-ended, self-administered questionnaires. RESULTS: Seventy percent of NMA physicians cited mistrust of the research centers, fear of losing patients, and a lack of respect from ECOG institutions as the most important barriers to minority cancer patient referrals, compared with 30% for ECOG physicians. Sixty-nine percent of NMA and 43% of ECOG physicians cited a lack of information about specific trials. Nearly half of NMA physicians (47%) cited a lack of minority investigators as a barrier, compared with 4% of ECOG physicians. Solutions by both groups were improved communication (73%) and culturally relevant educational materials (40%). ECOG physicians cited more minority outreach staff as a potential solution (22% v 6%). NMA physicians cited increased involvement of referring physicians (44% v4%). CONCLUSION: NMA physicians who serve a significant sector of the African American population demonstrated a willingness to participate and work with a cooperative group effort to increase participation of minority patients and investigators.

Promoting cancer screening among the first-degree relatives of breast and colorectal cancer patients: the design of two randomized trials.

BACKGROUND: In this paper two large nationwide trials are described, both of which will test a comparable telephone-based counseling intervention to promote cancer screening among the first-degree relatives (FDRs) of breast and colorectal cancer patients. The unit of randomization will be the family unit of eligible FDRs. Access to FDRs will be obtained from their relatives with cancer. Selected intervention and design issues are reviewed, including how both projects will respond to FDRs who exhibit significant levels of cancer-specific anxiety or distress and how potential high-risk cancer families will be accommodated. METHODS: Pursuant to the development of both studies, two feasibility surveys were conducted to determine whether patients would grant access to their FDRs and whether the FDRS identified by these patients would be receptive to the telephone intervention. RESULTS: Approximately 80% (106 of 132) of breast cancer patients agreed to provide access to their eligible FDRs when contacted on-site at participating hospitals and clinics. Of those subsequently selected for telephone follow-up (n = 95 or 90%), 80% (n = 76) were successfully contacted by telephone, and of these 97% (n = 74) provided the names and telephone numbers of their FDRs. Among colorectal cancer patients contacted on-site (n = 46), 96% (n = 44) agreed to provide access to their FDRs, and of those contacted by telephone (n = 33 or 75%), 91% (n = 30) provided the requested information about their FDRs. Once contacted, 95% of breast cancer FDRs (55 of 58) and 91% of colorectal cancer patients (51 of 56) endorsed the intervention strategy. CONCLUSIONS: It is argued that this intervention, if proven effective, could provide an exportable strategy for reaching large numbers of high-risk individuals to promote cancer screening.

New directions for risk communication research: a discussion with additional suggestions.

The papers by Huerta and Macario and Kreuter share the theme of suggesting new directions for risk communication research in cancer prevention and control. Huerta and Macario remind us once again that sociocultural factors must be considered when conducting risk communication research on underserved populations. Of special note is their recommendation to target the family, which could introduce a compelling new chapter in risk communication research in cancer prevention and control. In contrast, Kreuter challenges us to consider multiple cancer risks and risk-reducing behaviors in our research and provides a provocative framework for achieving this goal. Given this common theme and the need to position specific recommendations within the larger context of other competing research questions, this paper also highlights several additional recommendations for future research. These recommendations include the following: more research on risk presentation; establishing guidelines for measuring risk; additional research testing strategies to de-bias optimistic and pessimistic perceptions of risk and evaluating risk communication as a strategy for behavior change; more research investigating the sociology of risk communication, with a special emphasis on the family as the unit of investigation; and, finally, more research that specifically targets underserved populations in diverse community settings.

The cancer information service research consortium: an emerging laboratory for cancer control research.

The Cancer Information Service (CIS) was established in 1975 by the National Cancer Institute (NCI) to provide accurate, up-to-date information about cancer to the nation. Although the CIS has in the past served as a venue for cancer communications research, up until very recently the research capacity of the CIS was underutilized. In 1993, this situation changed dramatically with funding from the NCI to form the Cancer Information Service Research Consortium (CISRC). In this article the CISRC is described for the first time, including its research agenda and administrative structure. Early indications from the CISRC suggest that the CIS can serve as one of the premiere laboratories in the country for cancer communications and cancer control research. Several factors are suggested for the early success of the CISRC in sustaining this collaborative effort with the CIS. The progress that has been made by the CISRC could provide a useful model for other large health information programs to maximize their contributions to behavioral science and health promotion research, as well as to establish their own program of policy-relevant research.

Increasing fruit and vegetable consumption among callers to the CIS: results from a randomized trial.

BACKGROUND: Results are reported from a large randomized trial designed to increase fruit and vegetable consumption among callers to the Cancer Information Service (CIS). METHODS: CIS callers assigned to the intervention group received a brief proactive educational intervention over the telephone at the end of usual service, with two follow-up mailouts. Key educational messages and print material derived from the NCI 5 A Day for Better Health program were provided to intervention subjects. Subjects were interviewed by telephone at both 4-week (n = 1,672) and 4-month (n = 1,286) follow-up. RESULTS: A single-item measure of fruit and vegetable consumption revealed a significant intervention effect of approximately 0.65 servings per day at 4-week follow-up (P < 0.001) and 0.41 servings per day at 4-month follow-up (P < 0.001). Using a seven-item food frequency measure that was also included in the 4-month interviews, a similar intervention effect of 0.34 servings per day was obtained (P = 0.006). The vast majority of CIS callers (88%) endorsed the strategy of providing 5 A Day information proactively. CONCLUSIONS: A brief educational intervention delivered to CIS callers at the end of usual service was associated with an increase in self-reported fruit and vegetable intake.

The cancer information service research consortium: a brief retrospective and a preview of the future.

The Cancer Information Service Research Consortium (CISRC) was initially funded by the National Cancer Institute (NCI) in 1993 to examine seven key research questions. In this paper, the final results pertaining to these seven research questions are briefly reviewed, as well as several key lessons that have been learned from this unique research collaboration. Also described is the second generation of CISRC research that was recently funded by the NCI and is now in its first year of development. The results obtained from the first generation of research should provide the Cancer Information Service, as well as other organizations and agencies, with several viable programmatic options for the future.

A feasibility test of a brief educational intervention to increase fruit and vegetable consumption among callers to the Cancer Information Service.

BACKGROUND: In this paper, results are reported from a pilot study designed to test the feasibility of a proactive educational intervention delivered to callers of the Cancer Information Service (CIS). METHODS: The study used a randomized two-group design (intervention vs control). Callers assigned to the intervention condition received a brief educational intervention at the end of usual service to increase fruit and vegetable consumption. As part of the intervention, key education messages and materials drawn from the 5 A Day for Better Health program of the National Cancer Institute were provided to CIS callers over the telephone and then reinforced with two follow-up mailings. RESULTS: Results from this pilot study indicated high levels of adherence to protocol by CIS Information Specialists who delivered the intervention to eligible CIS callers. Results obtained from the 4-week telephone follow-up interviews indicated that intervention subjects (n = 142) reported higher consumption of fruits and vegetables, averaging approximately 0.75 servings more per day (P < 0.01) than control subjects (n = 134). CONCLUSION: Nearly 80% of CIS callers endorsed the strategy of providing 5 A Day information at the end of usual service, even if such information was not specifically requested by the caller (i.e., the information was provided to CIS callers proactively.

Reducing loss-to-follow-up among women with abnormal Pap smears. Results from a randomized trial testing an intensive follow-up protocol and economic incentives.

OBJECTIVES: This study evaluates the efficacy of two interventions designed to reduce loss-to-follow-up among women with abnormal Pap smears. METHODS: The two interventions were evaluated in two large public hospitals using a randomized 2 x 2 factorial design. One intervention involved an intensive follow-up protocol that relied on multiple attempts (mail and telephone) to contact the patient. The second intervention provided patients with economic vouchers to offset out-of-pocket expenses associated with the follow-up visits. Loss-to-follow-up was addressed by medical chart reviews and telephone interviews. RESULTS: The study population (n = 1453) was primarily Hispanic, married or otherwise living with a significant other, relatively young in age, and with no source of payment for health care. Overall, 30% of the total sample was loss-to-follow-up (i.e., no return visits). Among patients assigned to the control condition, loss-to-follow-up was 36.1% compared with 27.8% for the intensive follow-up condition, 28.8% for the voucher condition, and 29.0% for the intensive follow-up plus voucher condition. Both intervention conditions significantly improved follow-up rates. The odds ratio for intensive follow-up was 1.56 compared with 1.50 for the voucher intervention. The combined intervention condition (intensive follow-up x voucher program) did not have a significant effect after taking into account the main effects of the two interventions. Correlates of loss-to-follow-up included age (younger women had lower return rates), race/ethnicity (African American women had lower return rates), live-in relationship (women who were not married or living as married had lower return rates), and severity of the abnormal Pap smear (less severe abnormalities were associated with lower return rates). CONCLUSIONS: Both interventions were associated with moderate reductions in loss-to-follow-up in this underserved population. The implications of these findings are discussed relative to implementing cervical cancer control programs within state and local health departments.

A review of cervical cancer screening intervention research: implications for public health programs and future research.

In this paper we review the published literature with respect to cervical cancer screening intervention research. Mass media campaigns appear to work best in promoting cervical cancer screening when multiple media are used, when they promote specific screening programs that eliminate or reduce access barriers, or when they are used in combination with other strategies. Many positive examples of using outreach staff to promote cervical cancer screening, as well as using mobile examination rooms in the community, were found. Substantial evidence that letters mailed to patient populations are efficacious was found, especially in promoting interval screening; however, bulk mailings to nonpatient populations have generally not been successful. Both physician and patient prompts have shown promise as well as opportunistic screenings in both the outpatient and the inpatient settings. In addition, several strategies for reducing loss to follow-up among women with abnormal test results were identified, including telephone follow-up, educational mailouts, audiovisual programs, clinic-based educational presentations and workshops, transportation incentives, and economic vouchers. Of special note is the success of other countries in establishing centralized recall systems to promote interval screening for cervical cancer. Ultimately, such systems could replace the need for opportunistic screening in underserved populations and perhaps many community outreach efforts. It is argued that health departments represent a logical starting point for developing a network of recall systems in the United States for underserved women.

Telephone counseling of breast cancer patients after treatment: a description of a randomized clinical trial.

The Telephone Counseling Trial for Breast Cancer Survivors is a randomized, controlled study designed to test the impact of a telephone-based counseling intervention on quality of life of early-stage breast cancer patients who have completed adjuvant treatment. A psychoeducational counseling model is utilized to promote adaptive coping to re-entry stressors and survivorship issues. Adaptation is fostered through the exploration of thematic materials, application of active coping strategies, encouragement of a personal expression of the breast cancer experience and the provision of psychological support. Patients are being recruited in collaboration with two NCI-designated clinical cooperative oncology groups: the Eastern Cooperative Oncology Group (ECOG) and the Southwest Cooperative Oncology Group (SWOG). The recruitment goal is 400 breast cancer survivors with Stage 1, Stage 2 and Stage 3 disease (with no greater than 10 positive lymph nodes involved). Patients are being enrolled by data managers on-site during their last treatment visit. The intervention is being delivered by the Cancer Information and Counseling Line (CICL) of the AMC Cancer Research Center. It includes 16 telephone outcalls which are delivered over a 12-month period. Primary outcome measures are quality of life, mood, social support, self-efficacy, and sexual functioning, assessed at baseline, 3, 6, 12 and 18 months follow-up. This article provides a description of the intervention protocol and study design. It is argued that this study could provide a model for developing and testing other psychosocial interventions within clinical cooperative groups nationwide.