Canadian cancer screening disparities: a recent historical perspective.

Across Canada, introduction of the Pap test for cervical cancer screening, followed by mammography for breast cancer screening and, more recently, the fecal occult blood test for colorectal cancer screening, has contributed to a reduction in cancer mortality. However, another contribution of screening has been disparities in cancer mortality between certain populations. Here, we explore the disparities associated with breast and cervical cancer screening and preliminary data concerning disparities in colorectal cancer screening. Although some disparities in screening utilization have been successfully reduced over time (for example, mammography and Pap test screening in rural and remote populations), screening utilization data for other populations (for example, low-income groups) clearly indicate that disparities have existed and continue to exist across Canada. Organized screening programs in Canada have been able to successfully engage 80% of women for regular cervical cancer screening and 70% of women for regular mammography screening, but of the women who remain to be reached or engaged in regular screening, those with the least resources, those who are the most isolated, and those who are least culturally integrated into Canadian society as a whole are over-represented. Population differences are also observed for utilization of colorectal cancer screening services. The research literature on interventions to promote screening utilization provides some evidence about what can be done to increase participation in organized screening by vulnerable populations. Adaption and adoption of evidence-based screening promotion interventions can increase the utilization of available screening services by populations that have experienced the greatest burden of disease with the least access to screening services.

[Paleopathology of deafness: skulls of the Dupuytren Museum]. / Paléopathologie de la surdité: inédits ostéo-archéologiques.

In the 18th and 19th centuries, the Dupuytren Museum was indispensable for the knowledge of pathological anatomy for physicians and surgeons. Nowadays, it is more a museum than a learning unit, but it provides an opportunity to understand through numerous scientific studies the origin of diseases, injuries mechanism and the functional consequences of which could suffer some patients. This study illustrates the interest of the study on pieces in pathological anatomy's museums, this time across selected skulls which belonged to hearing loss people. bizarre.

The use of Omegaven in treating parenteral nutrition-associated liver disease.

Parenteral nutrition (PN), containing fat emulsions derived from soybean, has been implicated in the progression of PN-associated liver disease and cholestasis, particularly in infants with short bowel syndrome. Clinical use of Omegaven, a parenteral fish-oil emulsion, has been shown in recent studies to be a promising therapy to reverse liver disease and cholestasis. This review summarizes the rationale, relevant clinical investigations and future direction of Omegaven therapy for PN-dependent infants.

Aging skeletal muscle mitochondria in the rat: decreased uncoupling protein-3 content.

The goal of the present study was to discern the cellular mechanism(s) that contributes to the age-associated decrease in skeletal muscle aerobic capacity. Skeletal muscle mitochondrial content, a parameter of oxidative capacity, was significantly lower (25 and 20% calculated on the basis of citrate synthase and succinate dehydrogenase activities, respectively) in 24-mo-old Fischer 344 rats compared with 6-mo-old adult rats. Mitochondria isolated from skeletal muscle of both age groups had identical state 3 (ADP-stimulated) and ADP-stimulated maximal respiratory rates and phosphorylation potential (ADP-to-O ratios) with both nonlipid and lipid substrates. In contrast, mitochondria from 24-mo-old rats displayed significantly lower state 4 (ADP-limited) respiratory rates and, consequently, higher respiratory control ratios. Consistent with the tighter coupling, there was a 68% reduction in uncoupling protein-3 (UCP-3) abundance in mitochondria from elderly compared with adult rats. Congruent with the respiratory studies, there was no age-associated decrease in carnitine palmitoyltransferase I and carnitine palmitoyltransferase II activities in isolated skeletal muscle mitochondria. However, there was a small, significant decrease in tissue total carnitine content. It is concluded that the in vivo observed decrease in skeletal muscle aerobic capacity with advanced age is a consequence of the decreased mitochondrial density. On the basis of the dramatic reduction of UCP-3 content associated with decreased state 4 respiration of skeletal muscle mitochondria from elderly rats, we propose that an increased free radical production might contribute to the metabolic compromise in aging.

The emotional consequences of false positive mammography: African-American women's reactions in their own words.

High false positive rates associated with screening for breast cancer in the United States have an unintended psychological consequence for women (Lerman et al., 1991) that has raised concerns in recent years (Sox, 1998). This study uses inductive qualitative analysis of open-ended interviews with 45 African American women living in New York City who were part of a larger study of women and their experiences after receiving an abnormal mammogram. Themes resulting from the analyses included: inadequate provider-patient communication, anxieties exacerbated by waiting and wondering, and fears of iatrogenic effects of follow-up tests such as biopsies and repeat mammograms. While more research is needed on message-framing strategies for women entering mammographic testing and follow-up, modest changes in service delivery such as improved medical communication can help to alleviate fears and enhance trust.

Rat liver mitochondrial contact sites and carnitine palmitoyltransferase-I.

In hepatic mitochondria, the outer membrane enzyme, carnitine palmitoyltransferase-I (CPT-I), appears to colocalize with contact sites. We have prepared contact sites that are essentially devoid of noncontact site membranes. The contact site fraction has a high specific activity for CPT-I and contains a protein at 88 kDa that is recognized by antibodies directed at two different peptide epitopes on CPT-I. Similarly long-chain acyl-CoA synthetase (LCAS) specific activity is high in this fraction; a protein at 79 kDa is recognized by an antibody against LCAS. Although activity of carnitine palmitoyltransferase-II (CPT-II) is present, it is not enriched in the contact site fraction, and a protein of 68 kDa weakly reacted with anti-CPT-II antibody. Likewise, carnitine-acylcarnitine translocase (CACT) protein is present, but at a somewhat reduced level. Using an analytical continuous sucrose gradient, we demonstrate that the activities of CPT-I and LCAS and their associated immunoreactive proteins are present in a constant amount throughout the contact site subfractions. The enzymatic activity of CPT-II and its associated immunoreactive protein, as well as immunoreactive CACT, is absent in the lighter density gradient subfractions and is present in the higher density subfractions only in trace amounts. This heterogeneity of the contact site fraction is due to unvarying amounts of outer membrane and increasing amounts of attached inner membrane with increasing density of the subfractions.

Mitochondrial dysfunction in cardiac disease: ischemia--reperfusion, aging, and heart failure.

Mitochondria contribute to cardiac dysfunction and myocyte injury via a loss of metabolic capacity and by the production and release of toxic products. This article discusses aspects of mitochondrial structure and metabolism that are pertinent to the role of mitochondria in cardiac disease. Generalized mechanisms of mitochondrial-derived myocyte injury are also discussed, as are the strengths and weaknesses of experimental models used to study the contribution of mitochondria to cardiac injury. Finally, the involvement of mitochondria in the pathogenesis of specific cardiac disease states (ischemia, reperfusion, aging, ischemic preconditioning, and cardiomyopathy) is addressed.

Improving knowledge of the prostate cancer screening dilemma among African American men: an academic-community partnership in Washington, DC.

OBJECTIVE: Studies have shown that African American men are at greater risk than other men for prostate cancer in terms of both incidence and mortality. At the same time, the utility of screening asymptomatic men for prostate cancer remains controversial. The combination of high incidence and high mortality with the uncertain benefits of screening poses a difficult problem for African American men. This study was part of an ongoing project that sought to develop and evaluate health education materials designed to help African American men make an informed decision about prostate cancer screening. The project represented a collaboration between the Most Worshipful Prince Hall Grand Lodge of the District of Columbia and the Lombardi Cancer Center of Georgetown University. METHODS: The authors conducted eight focus groups with 44 members of the Prince Hall Masons. The focus groups covered men's understanding of prostate cancer screening and their preferences for methods of health education. RESULTS: Participants demonstrated a high level of awareness of the availability of prostate cancer screening, a low awareness of the screening controversy, and a desire for detailed epidemiologic information and information about the benefits and limitations of screening. The preferred forms of educational materials were video and print-based materials, which the research team has recently developed. CONCLUSIONS: These findings demonstrate the feasibility of developing an academic-community collaboration with the goal of improving a health-related problem in the African American community. A randomized trial is underway to evaluate the impact of the video and print education materials.

Screening mammography and breast cancer treatment patterns in older women.

OBJECTIVE: To examine the impact of mammography screening on treatment options received by a cohort of older breast cancer patients. SETTING AND POPULATION: We studied 718 newly diagnosed breast cancer patients, 67 years and over, diagnosed with TNM Stage I and II disease between 1995 and 1997 at 29 hospitals in five regions. METHODS: Data were collected from patients, surgeons, and medical records. A breast cancer diagnosis was considered to have been by screening mammography if so reported by both patient and medical records. Bivariate and logistic regression were used to identify predictors of a women having her cancer detected by screening mammography and the relationships between mode of detection, stage of disease at diagnosis, and local treatment. RESULTS: Women with high school or greater education were 1.75 times (95%, CI 1.11-2.75) more likely to have their cancers diagnosed by screening mammography than women who had not completed high school, controlling for other factors. Screening found earlier stage disease: 96% of women with mammographically diagnosed cancer had T1 lesions, compared to 81% of women diagnosed by other means (p = 0.001). Women with mammography detected lesions were more likely to have ductal cancer, and to be referred to radiation oncologists more than women diagnosed by other means. Controlling for stage and histology, screening remained associated with a higher likelihood of receiving breast conserving surgery (BCS) with radiation (RT) (OR 1.56, 95%, CI 1.10-2.22) than other local therapies. CONCLUSIONS: Beyond the impact on stage, ductal cancers were more likely to be diagnosed by screening. Mammographically detected lesions were associated with referrals to radiation oncologists and higher rates of BCS and RT. Research is needed to explain the residual independent effects of mammography screening on breast cancer treatment.

Effectiveness of interventions to improve follow-up after abnormal cervical cancer screening.

OBJECTIVE: The purpose of this study was to determine the effectiveness of interventions designed to improve follow-up after an abnormal Pap smear. METHODS: We performed a qualitative meta-analysis of interventions designed to improve follow-up after an abnormal Pap smear and included studies that met the following criteria: randomized or concurrently controlled study design, defined outcomes, and data available for abstraction. Interventions were classified as behavioral, cognitive, sociologic, or combined strategies (e.g., behavioral and cognitive). Abnormal Pap smears were defined as any test result requiring additional follow-up. Effectiveness was measured by the rate of compliance with recommended follow-up. RESULTS: Twenty-two interventions in 10 studies met the inclusion criteria. Cognitive interventions utilizing interactive telephone counseling were the most effective, improving compliance by 24 to 31%. Behavioral interventions, such as patient reminders, were also effective, increasing follow-up by up to 18%. Not all of these results achieved statistical significance. The single sociologic intervention we identified used video-taped peer discussions to provide a message about abnormal Pap smears and appropriate follow-up. This intervention was not associated with increased follow-up after an abnormal test. The effectiveness of interventions using multiple types of strategies to improve follow-up was inconsistent. CONCLUSIONS: Cognitive strategies led to the greatest improvement in compliance with follow-up of abnormal Pap smear screening tests. Extension of similar interventions to follow-up of abnormal breast and colon cancer screening, development of physician- and system-targeted interventions, and evaluation of the cost-effectiveness of these strategies are important priorities for future research.

Patterns of breast carcinoma treatment in older women: patient preference and clinical and physical influences.

BACKGROUND: Older women have high rates of breast carcinoma, and there are substantial variations in the patterns of care for this population group. METHODS: The authors studied 718 breast carcinoma patients age 67 years and older who were diagnosed with localized disease between 1995 and 1997 from 29 hospitals in 5 regions. Data were collected from patients, charts, and surgeons. Logistic regression analysis was used to evaluate determinants of treatment. RESULTS: Women who were concerned about body image were 1.8 times more likely (95% confidence interval [95% CI], 1.1-2.8) to receive breast conservation surgery and radiotherapy than women without this preference, controlling for other factors. In contrast, women who preferred receiving no therapy beyond surgery were 3.9 times more likely (95% CI, 2.9-6.1) to undergo mastectomy than other women, after considering other factors. Radiotherapy was omitted after breast conservation 3.4 times more often (95% CI, 2.0-5.6) among women age 80 years and older than among women ages 67-79 years, controlling for covariates. Black women tended to have radiotherapy omitted after breast conservation surgery 2.0 times more often (95% CI, 0.9-4.4) than white women (P = 0.09). Women age 80 years and older also were 70% less likely (odds ratio = 0.3; 95% CI, 0.1-0.8) to receive chemotherapy than women ages 67-79 years, controlling for health, functional status, and other covariates. CONCLUSIONS: After considering other factors, patient preferences and age were found to be associated with breast carcinoma treatment patterns in older women. Further research and training are needed to provide care for the growing population of older women that is both clinically appropriate and consonant with a woman's preferences.

Fatty acid import into mitochondria.

The mitochondrial carnitine system plays an obligatory role in beta-oxidation of long-chain fatty acids by catalyzing their transport into the mitochondrial matrix. This transport system consists of the malonyl-CoA sensitive carnitine palmitoyltransferase I (CPT-I) localized in the mitochondrial outer membrane, the carnitine:acylcarnitine translocase, an integral inner membrane protein, and carnitine palmitoyltransferase II localized on the matrix side of the inner membrane. Carnitine palmitoyltransferase I is subject to regulation at the transcriptional level and to acute control by malonyl-CoA. The N-terminal domain of CPT-I is essential for malonyl-CoA inhibition. In liver CPT-I activity is also regulated by changes in the enzyme's sensitivity to malonyl-CoA. As fluctuations in tissue malonyl-CoA content are parallel with changes in acetyl-CoA carboxylase activity, which in turn is under the control of 5'-AMP-activated protein kinase, the CPT-I/malonyl-CoA system is part of a fuel sensing gauge, turning off and on fatty acid oxidation depending on the tissue's energy demand. Additional mechanism(s) of short-term control of CPT-I activity are emerging. One proposed mechanism involves phosphorylation/dephosphorylation dependent direct interaction of cytoskeletal components with the mitochondrial outer membrane or CPT-I. We have proposed that contact sites between the outer and inner mitochondrial membranes form a microenvironment which facilitates the carnitine transport system. In addition, this system includes the long-chain acyl-CoA synthetase and porin as components.

Growth in human milk-Fed very low birth weight infants receiving a new human milk fortifier.

BACKGROUND/AIMS: Human milk fortification has been advocated to enhance premature infants' growth. We, therefore, undertook this study of a new human milk fortifier containing more protein than a reference one. METHODS: Open, randomized, controlled, multiclinic trial, with weekly growth parameters and safety evaluations in premature infants <1,500 g. RESULTS: The 2 groups did not differ in demographic and baseline characteristics. The adjusted daily milk intake was significantly higher in the infants fed reference human milk fortifier (n = 29; 154.2 +/- 2.1 vs. 144.4 +/- 2.5 ml/kg/day, mean +/- SE; p < 0.05). Both human milk fortifiers produced increases over baseline in weight, length, and head circumference, with greater gains observed in the new human milk fortifier-fed infants for the former two parameters (weight gain 26.8 +/- 1.3 and 20.4 +/- 1.2 g/day, p < 0.05; head circumference 1.0 +/- 0.1 and 0.8 +/- 0.1 cm/week; length 0.9 +/- 0.1 and 0.8 +/- 0.1 cm/week, respectively). Serum chemistries were normal and acceptable for age. Study events were typical for premature infants and similar in both groups. CONCLUSIONS: This new human milk fortifier had comparable safety to the reference human milk fortifier and promoted faster weight gain and head circumference growth.

Equitable access to cancer services: A review of barriers to quality care.

BACKGROUND: Barriers to cancer care have been documented in nearly all settings and populations; such barriers represent potentially avoidable morbidity or mortality. A conceptual framework was used to describe patient, provider, and system barriers to cancer services. METHODS: A review of the English language literature on cancer care from 1980-1998 was conducted; key research was summarized for each domain in the conceptual model. RESULTS: Key patient barriers are related to old age, minority race, and low socioeconomic class; the common pathways by which these sociodemographic factors appear to mediate cancer outcomes include social class and race-related or class-related attitudes. Providers are often ill-prepared to communicate the complexities of cancer care to their diverse patient populations; constraints of the medical care system also can impede the delivery of care. To the authors' knowledge the impact of the rapid growth in managed care organizations (MCOs) on access to care has yet to be evaluated fully. Although MCOs historically have provided high levels of cancer screening in healthy populations, to the authors' knowledge there are fewer data regarding outcomes for elderly and poor populations and for treatment services. CONCLUSIONS: Additional research is needed to develop and test interventions to overcome barriers to care and evaluate the impact of the growth of managed care on access to cancer care for diverse populations.

A 22 kDa polyanion inhibits carnitine-dependent fatty acid oxidation in rat liver mitochondria.

The transport of activated fatty acids across the mitochondrial outer membrane has not been fully addressed. A polyanion (M(n)=22 kDa) inhibited the ADP-stimulated carnitine-dependent oxidation of both palmitoyl-CoA and palmitate plus CoA as well as mitochondrial hexokinase binding. In contrast, the oxidation of palmitoylcarnitine plus malate, as well as glutamate oxidation, was essentially unaffected. Mitochondrial carnitine palmitoyltransferase-1 was not inhibited by the polyanion. The data suggest an additional component in carnitine-dependent mitochondrial fatty acid oxidation, possibly porin.

Altered neurotransmitter receptor expression in transgenic mouse models of Huntington's disease.

Alterations in neurotransmitter receptors are a pathological hallmark of the neurodegeneration seen in Huntington's disease (HD). However, the significance of these alterations has been uncertain, possibly reflecting simply the loss of brain cells. It is not known for certain whether the alteration of neurotransmitter receptors occurs before the onset of symptoms in human HD. Recently we developed transgenic mice that contain a portion of a human HD gene and develop a progressive abnormal neurological phenotype. Neurotransmitter receptors that are altered in HD (receptors for glutamate, dopamine, acetylcholine and adenosine) are decreased in the brain transgenic mice, in some cases before the onset of behavioural or motor symptoms. In transgenic mice, neurotransmitter receptor alterations occur before neuronal death. Further, receptor alterations are selective in that certain receptors, namely N-methyl-D-aspartate and gamma-aminobutyric acid receptors, are unaltered. Finally, receptor decreases are preceded by selective decreases in the corresponding mRNA species, suggesting the altered transcription of specific genes. These results suggest that (i) receptor decreases precede, and therefore might contribute to, the development of clinical symptoms, and (ii) altered transcription of specific genes might be a key pathological mechanism in HD.

Correlation between pre-operative periprosthetic bone density and post-operative bone loss in THA can be explained by strain-adaptive remodelling.

Periprosthetic adaptive bone remodelling after total hip arthroplasty can be simulated in computer models, combining bone remodelling theory with finite element analysis. Patient specific three-dimensional finite element models of retrieved bone specimens from an earlier bone densitometry (DEXA) study were constructed and bone remodelling simulations performed. Results of the simulations were analysed both qualitatively and quantitatively. Patterns of predicted bone loss corresponded very well with the DEXA measurements on the retrievals. The amount of predicted bone loss, measured quantitatively by simulating DEXA on finite element models, was found to be inversely correlated with the initial bone mineral content. It was concluded that the same clinically observed correlation can therefore be explained by mechanically induced remodelling. This finding extends the applicability of numerical pre-clinical testing to the analysis of interaction between implant design and initial state of the bone.

Racial differences in testing motivation and psychological distress following pretest education for BRCA1 gene testing.

OBJECTIVES: We conducted a randomized trial to investigate racial differences in response to two alternate pretest education strategies for BRCA1 genetic testing: a standard education model and an education plus counseling (E + C) model. MATERIALS AND METHODS: Two hundred twenty-eight Caucasian women and 70 African American women with a family history of breast or ovarian cancer were contacted for a baseline telephone interview to assess sociodemographic characteristics, number of relatives affected with cancer, and race before pretest education. Outcome variables included changes from baseline to 1-month follow-up in cancer-related distress and genetic testing intentions, as well as provision of a blood sample after the education session. RESULTS: African American women were found to differ significantly from Caucasian women in the effects of the interventions on testing intentions and provision of a blood sample. Specifically, in African American women, E + C led to greater increases than education only in intentions to be tested and provision of a blood sample. These effects were independent of socioeconomic status and referral mechanisms. In Caucasian women, there were no differential effects of the interventions on these outcomes. Reductions in cancer-specific distress were evidenced in all study groups. However, this decrease, although not significantly different, was smallest among African American women who received E + C. CONCLUSIONS: In low- to moderate-risk African American women, pretest education and counseling may motivate BRCA1 testing. Further research is needed to explore the mechanisms of impact of the alternate pretest education strategies and to increase the cultural sensitivity of education and counseling protocols.

Breast and cervix cancer screening among multiethnic women: role of age, health, and source of care.

OBJECTIVE: The aim of this study was to evaluate the relationships between age, health status, access to care, and breast and cervical cancer screening among multiethnic elderly and nonelderly women. METHODS: A structured telephone survey of a quota sample of 1,420 New York City women from four Hispanic groups (Columbian, Dominican, Puerto Rican, Ecuadorian) and three black groups (U.S., Caribbean, and Haitian) was performed. Outcome measures included "ever" and "recent" self-reported use of mammography, clinical breast examination (CBE), and Pap smears. Logistic regression models assessed the predictors of screening use. RESULTS: Having a regular source of care significantly predicted all screening use for both elderly and nonelderly, controlling for ethnicity, sociodemographics, health status, access to care, proportion of life in the United States, and cancer attitudes. Elderly women (>/=65 years) were significantly less likely to have ever had (OR = 0.79, 95% CI 0.65-0. 96) and to have recently had (OR = 0.67, 95% CI 0.57-0.79) Pap smears than younger women, controlling for the other variables; being elderly also tended to be an independent predictor of ever and recent mammography and CBE use. Interestingly, there was a trend for health status to act differently in predicting Pap smear use for the two age groups. For younger women, being in poor health increased the odds of Pap smear screening, while for elderly women, being in good health increased the odds of screening. CONCLUSIONS: Elderly women reported being screened less than younger women; interactions between health status and age need further exploration.