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.

Involvement of p59fynT in interleukin-5 receptor signaling.

Previous studies implicate the nonreceptor protein tyrosine kinase (PTK) p59fyn in the propagation of signals from the B cell antigen receptor. To elucidate the functions of this kinase, we examined B cell responsiveness in mice engineered to lack the hematopoietic isoform of p59fyn. Remarkably, antigen receptor signaling was only modestly defective in fynTnull B cells. In contrast, signaling from the interleukin (IL)-5 receptor which ordinarily provides a comitogenic stimulus with antiimmunoglobulin, was completely blocked. Our results document the importance of p59fynT in IL-5 responses in B cells, and they support a general model for cytokine receptor signal transduction involving the simultaneous recruitment of at least three families of PTK.

Controlled trial of pretest education approaches to enhance informed decision-making for BRCA1 gene testing.

BACKGROUND: In response to the isolation of the BRCA1 gene, a breast-ovarian cancer-susceptibility gene, biotechnology companies are already marketing genetic tests to health care providers and to the public. Initial studies indicate interest in BRCA1 testing in the general public and in populations at high risk. However, the optimal strategies for educating and counseling individuals have yet to be determined. PURPOSE: Our goal was to evaluate the impact of alternate strategies for pretest education and counseling on decision-making regarding BRCA1 testing among women at low to moderate risk who have a family history of breast and/or ovarian cancer. METHODS: A randomized trial design was used to evaluate the effects of education only (educational approach) and education plus counseling (counseling approach), as compared with a waiting-list (control) condition (n = 400 for all groups combined). The educational approach reviewed information about personal risk factors, inheritance of cancer susceptibility, the benefits, limitations, and risks of BRCA1 testing, and cancer screening and prevention options. The counseling approach included this information, as well as a personalized discussion of experiences with cancer in the family and the potential psychological and social impact of testing. Data on knowledge of inherited cancer and BRCA1 test characteristics, perceived risk, perceived benefits, limitations and risks of BRCA1 testing, and testing intentions were collected by use of structured telephone interviews at baseline and at 1-month follow-up. Provision of a blood sample for future testing served as a proxy measure of intention to be tested (in the education and counseling arms of the study). The effects of intervention group on study outcomes were evaluated by use of hierarchical linear regression modeling and logistic regression modeling (for the blood sample outcome). All P values are for two-sided tests. RESULTS: The educational and counseling approaches both led to significant increases in knowledge, relative to the control condition (P < .001 for both). The counseling approach, but not the educational approach, was superior to the control condition in producing significant increases in perceived limitations and risks of BRCA1 testing (P < .01) and decreases in perceived benefits (P < .05). However, neither approach produced changes in intentions to have BRCA1 testing. Prior to and following both education only and education plus counseling, approximately one half of the participants stated that they intended to be tested; after the session, 52% provided a blood sample. CONCLUSIONS: Standard educational approaches may be equally effective as expanded counseling approaches in enhancing knowledge. Since knowledge is a key aspect of medical decision-making, standard education may be adequate in situations where genetic testing must be streamlined. On the other hand, it has been argued that optimal decision-making requires not only knowledge, but also a reasoned evaluation of the positive and negative consequences of alternate decisions. Although the counseling approach is more likely to achieve this goal, it may not diminish interest in testing, even among women at low to moderate risk. Future research should focus on the merits of these alternate approaches for subgroups of individuals with different backgrounds who are being counseled in the variety of settings where BRCA1 testing is likely to be offered.

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.

Effect of malonyl-CoA on the kinetics and substrate cooperativity of membrane-bound carnitine palmitoyltransferase of rat heart mitochondria.

The effect of malonyl-CoA on the kinetic parameters of carnitine palmitoyltransferase (outer) the outer form of carnitine palmitoyltransferase (palmitoyl-CoA: L-carnitine O-palmitoyltransferase, EC 2.3.1.21) from rat heart mitochondria was investigated using a kinetic analyzer in the absence of bovine serum albumin with non-swelling conditions and decanoyl-CoA as the cosubstrate. The K0.5 for decanoyl-CoA is 3 microM for heart mitochondria from both fed and fasted rats. Membrane-bound carnitine palmitoyltransferase (outer) shows substrate cooperativity for both carnitine and acyl-CoA, similar to that exhibited by the enzyme purified from bovine heart mitochondria. The Hill coefficient for decanoyl-CoA varied from 1.5 to 2.0, depending on the method of assay and the preparation of mitochondria. Malonyl-CoA increased the K0.5 for decanoyl-CoA with no apparent increase in sigmoidicity or Vmax. With 20 microM malonyl-CoA and a Hill coefficient of n = 2.1, the K0.5 for decanoyl-CoA increased to 185 microM. Carnitine palmitoyltransferase (outer) from fed rats had an apparent Ki for malonyl-CoA of 0.3 microM, while that from 48-h-fasted rats was 2.5 microM. The kinetics with L-carnitine were variable: for different preparations of mitochondria, the K0.5 ranged from 0.2 to 0.7 mM and the Hill coefficient varied from 1.2 to 1.8. When an isotope forward assay was used to determine the effect of malonyl-CoA on carnitine palmitoyltransferase (outer) activity of heart mitochondria from fed and fasted animals, the difference was much less than that obtained using a continuous rate assay. Carnitine palmitoyltransferase (outer) was less sensitive to malonyl-CoA at low compared to high carnitine concentrations, particularly with mitochondria from fasted animals. The data show that carnitine palmitoyltransferase (outer) exhibits substrate cooperativity for both acyl-CoA and L-carnitine in its native state. The data show that membrane-bound carnitine palmitoyltransferase (outer) like carnitine palmitoyltransferase purified from heart mitochondria exhibits substrate cooperativity indicative of allosteric enzymes and indicate that malonyl-CoA acts like a negative allosteric modifier by shifting the acyl-CoA saturation to the right. A slow form of membrane-bound carnitine palmitoyltransferase (outer) was not detected, and thus, like purified carnitine palmitoyltransferase, substrate-induced hysteretic behavior is not the cause of the positive substrate cooperativity.

The nature of maturational decline of intestinal lactase activity.

We have examined the nature of the decline of lactase (EC 3.2.1.23) activity in the maturing rat intestine. It was established in an initial study that the activity decline reflected a proportional reduction in the concentration of the enzyme protein. Accumulation patterns of label into lactase, total intestinal proteins and sucrase (EC 3.2.1.48)-isomaltase (EC 3.2.1.10) were compared, 4 h following administration of a tracer dose of [3H]leucine to weanling rats exhibiting a wide range of lactase decline. Accumulation of increasing amounts of label in total intestinal proteins and sucrase-isomaltase pools was found to accompany the lactase decline, in contrast to accumulation of a constant amount of label in the declining lactase pools. The pattern of increased label accumulation in total intestinal proteins was shown in a corollary study to reflect a corresponding acceleration of total protein synthesis. On this basis, the finding of a constant amount of label in the declining lactase pools suggested a constant synthesis of lactase. We proposed earlier that associated reductions in enterocyte life-span (leading to correspondingly less lactase accumulation) rather than suppressed synthesis may provide the primary causal basis of lactase decline in the postweaned mammal.

Continuity of care and the use of breast and cervical cancer screening services in a multiethnic community.

OBJECTIVE: To examine how continuity of care affects the use of breast and cervical cancer screening in a multiethnic population. METHODS: All data came from a structured telephone survey of a population-based quota sample designed to determine the cancer prevention needs of multiethnic blacks and Hispanics in New York, NY, in 1992. The study included 1420 women of 7 racial/ethnic groups: US-born blacks, English-speaking Caribbean-born blacks, Haitian blacks, and Puerto Rican, Dominican, Colombian, and Ecuadorian Hispanics. The main outcome measures were ever and recently having had a Papanicolaou smear, clinical breast examination (CBE), or mammogram. RESULTS: Among respondents who qualified for the survey on the basis of age and ethnicity, the refusal rate for completing the interview was 2.1%. Compared with women without a usual site of care, those with a usual site, but no regular clinician, were 1.56, 2.45 (P < or = .01), and 2.32 (P < or = .05) times as likely ever to have received a Papanicolaou smear, CBE, or mammogram, respectively and 1.84, 1.92 (P < or = .05), and 1.75 times as likely to have received a recent Papanicolaou smear, CBE, or mammogram, respectively. Compared with women without a usual site of care, women with a regular clinician at that usual site of care were 2.63 (P < or = .01), 2.83 (P < or = .01), and 2.30 (P < or = .05) times as likely ever to have received a Papanicolaou smear, CBE, or mammogram, and were 2.00 (P < or = .05), 2.65 (P < or = .01), and 1.40 times as likely to have recently received a Papanicolaou smear, CBE, or mammogram, respectively (adjusted odds ratios). For uninsured women, presence of a usual site of care was associated with increases in recent use of cancer screening for all screening tests. CONCLUSIONS: There is a linear trend in increasing breast and cervical cancer screening rates when one goes from having no usual source of care, to having a usual source, and to having a regular clinician at that usual source. Emphasis on continuity of care, especially on usual source of care, may help to bridge the gap in access to cancer prevention services faced by minority women.

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.

Expression of N-methyl-D-aspartate receptor subunit mRNAs in the human brain: striatum and globus pallidus.

N-methyl-D-aspartate receptors (NRs) play an important role in basal ganglia function. By using in situ hybridization with ribonucleotide probes, we investigated the regional and cellular distribution of NR subunit mRNA expression in the human basal ganglia: caudate nucleus, putamen, lateral globus pallidus (LGP), and medial globus pallidus (MGP). Analysis of both film autoradiograms and emulsion-dipped slides revealed distinct distribution patterns for each subunit. On film autoradiograms, the signal for NR1, NR2B, and NR2C in the striatum (STR) was higher than in globus pallidus (GP). The NR2D probe gave a stronger signal in GP than in STR. For NR2A we found a signal in all regions. Analysis of emulsion-dipped sections demonstrated that in striatal neurons, the NR2B signal was higher than in GP neurons. In GP neurons, NR2D was more abundant than in striatal neurons. Despite the relatively low signal on film for NR2C in GP, we found a slightly higher signal in GP per neuron than in STR since in the pallidal areas neurons were sparse but intensely labeled. NR1 and NR2A were more evenly distributed over neurons of STR and GP Between the different parts of STR and GP, we observed only minor differences in the expression of NRs. In MGP a subpopulation of neurons exhibiting low NR2D signals could be separated from the majority of neurons showing an intense NR2D signal. Since the physiological properties of NRs are dependent on subunit composition, these data suggest a high degree of regional specialization of NR properties in the human basal ganglia.

Expression of N-methyl-D-aspartate receptor subunit mRNAs in the human brain: hippocampus and cortex.

N-methyl-D-aspartate receptor (NR) activation in the hippocampus and neocortex plays a central role in memory and cognitive function. We analyzed the cellular expression of the five NR subunit (NR1 and NR2A-D) mRNAs in these regions with in situ hybridization and human ribonucleotide probes. Film autoradiograms demonstrated a distinct pattern of hybridization signal in the hippocampal complex and the neocortex with probes for NR1, NR2A, and NR2B mRNA. NR2C and NR2D probes yielded scattered signals without a distinct organization. At the emulsion level, the NR1 probe produced high-density hybridization signals across the hippocampal complex. NR2A mRNA was higher in dentate granule cells and pyramidal cells in CA1 and subiculum compared to hilus neurons. NR2B mRNA expression was moderate throughout, with higher expression in dentate granule cells, CA1 and CA3 pyramidal cells than in hilus neurons. In the hippocampal complex, the NR2C probe signal was not different from background in any region, whereas the NR2D probe signal resulted in low to moderate grain densities. We analyzed NR subunit mRNA expression in the prefrontal, parietal, primary visual, and motor cortices. All areas displayed strong NR1 hybridization signals. NR2A and NR2B mRNAs were expressed in cortical areas and layers. NR2C mRNA was expressed at low levels in distinct layers that differed by region and the NR2D signal was equally moderate throughout all regions. Pyramidal cells in both hippocampus and neocortex express NR1, NR2A, NR2B, and, to a lesser extent, NR2D mRNA. Interneurons or granular layer neurons and some glial cells express NR2C mRNA.

A national survey of attitudes and practices of primary-care physicians relating to nutrition: strategies for enhancing the use of clinical nutrition in medical practice.

A nationwide mail survey was used to determine the degree to which primary-care physicians indicated that they practice the "core competencies" in clinical nutrition identified by Young et al (Am J Clin Nutr 1983;38:800-10). We also surveyed the nutrition-related attitudes of these physicians. Although the 3416 physicians who responded to the survey tended to report favorable attitudes toward using nutrition in their practice, these favorable attitudes were not consistent with their own reports of clinical performance. Neither the positive- or negative-attitude score correlated highly with the reported behavior-practice score. The clinical practices reported by those surveyed are well below the minimum level defined by the Young et al essential core competencies in clinical nutrition. The attitudes, practices, and demographic characteristics associated with the clinical performance variables suggest educational strategies for improving the competence of primary-care physicians and medical students in clinical nutrition.

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.

Microvillous inclusion disease. The importance of electron microscopy for diagnosis.

We report two cases of microvillous inclusion disease (MID) occurring in a set of siblings. Although it is a rare disorder, MID appears to be a common cause of familial intractable secretory diarrhea. Diagnosis rests on the ultrastructural finding of intracytoplasmic inclusions that are lined by intact microvilli. These inclusions are present in the absorptive surface epithelial cells of the small and large intestine and are associated with poorly developed surface brush border microvilli. The prognosis of MID is poor and curative therapy is not currently available. Because MID appears to be a hereditary disorder, genetic counseling of affected families is essential.

Cloning and stable expression of the mGluR1b subtype of human metabotropic receptors and pharmacological comparison with the mGluR5a subtype.

We isolated and characterized a cDNA encoding the human metabotropic glutamate receptor subtype 1b (hmGluR1b). In situ hybridization studies in human brain regions revealed a higher distribution of mGluR1 mRNA in the dentate gyrus of the hippocampus, the substantia nigra pars compacta and the Purkinje cell layer of the cerebellum compared to other regions studied. We established stable expression of recombinant hmGluR1b in L(tk-) mouse fibroblast and Chinese hamster ovary (CHO-dhfr-) cells. In both expression systems, agonist activation of hmGluR1b stimulated inositol phosphate (InsP) formation and elevation of the cytosolic free calcium ([Ca2+]i), and both responses were blocked by (S)-MCPG. The rank order of potency for agonists was quisqualate > glutamate > (1S,3R)-ACPD in both expression systems. Comparison of the agonist profiles of hmGluR1b and hmGluR5a, both stably expressed in L(tk-) cells, indicated the same rank order of potency (quisqualate > glutamate > or = (RS)-3,5-DHPG > or = (1S,3R)-ACPD), but each of the four agonists were more potent on hmGluR5a than on hmGluR1b. In antagonist studies, (S)-MCPG inhibited the agonist-induced InsP formation and elevation of [Ca2+]i in both hmGluR1b- and hmGluR5a-expressing cells. (S)-4CPG and (S)-4C3HPG both inhibited agonist responses only in hmGluR1b-expressing cells. However, in hmGluR5a-expressing cells the antagonist activity of (S)-4CPG and (S)-4C3HPG was dependent on the agonist used in the study, since they inhibited responses to glutamate but not to quisqualate. Stable cell lines expressing specific subtypes of human mGluRs represent valuable tools for the study of the mechanism of action of mGluRs at the molecular and cellular level and as screening targets for identification of subtype-selective agonists or antagonists.

Late morbidity among survivors of necrotizing enterocolitis.

Of 40 survivors of necrotizing enterocolitis 19 were completely normal children at the time of follow-up, one to three years later. Among the other 21 children, only six had moderate to severe neurologic impairment, representing 15% of all survivors. Despite the fact that intestinal injury is the main feature of the neonatal disease, only four children were symptomatic from gastrointestinal sequelae, and none of these suffered failure to thrive. Thus, 81% (17) of the children with late morbidity had problems unrelated to the gastrointestinal tract. The nongastrointestinal morbidity was associated with prematurity and the degree of perinatal stress.

Effects of microwave radiation on anti-infective factors in human milk.

In intensive care nurseries it has become common practice to use microwave thawing of frozen human milk for more rapid accessibility. Twenty-two freshly frozen human milk samples were tested for lysozyme activity, total IgA, and specific secretory IgA to Escherichia coli serotypes 01, 04, and 06. The samples were heated by microwave for 30 seconds at a low- or high-power setting and then reanalyzed. One-mL aliquots of 10 additional human milk samples were microwaved at low (20 degrees C to 25 degrees C), medium (60 degrees C to 70 degrees C), and high (greater than or equal to 98 degrees C) setting before the addition to each of 1 mL of diluted E coli suspension. E coli growth was determined after 3 1/2 hours of incubation at 37 degrees C. Microwaving at high temperatures (72 degrees C to 98 degrees C) caused a marked decrease in activity of all the tested antiinfective factors. E coli growth at greater than or equal to 98 degrees C was 18 times that of control human milk. Microwaving at low temperatures (20 degrees C to 53 degrees C) had no significant effect on total IgA, specific IgA to E coli serotypes 01 and 04, but did significantly decrease lysozyme and specific IgA to E coli serotype 06. Even at 20 degrees C to 25 degrees C, E coli growth was five times that of control human milk. Microwaving appears to be contraindicated at high temperatures, and questions regarding its safety exist even at low temperatures.

Pivampicillin-promoted excretion of pivaloylcarnitine in humans.

Pivampicillin treatment of seven children (five boys and two girls) for 7 days significantly reduced the amounts of total acid-soluble carnitine, free carnitine, and long-chain acylcarnitines and increased the amounts of acid-soluble acylcarnitine in plasma. The fasting plasma levels of 3-hydroxybutyrate at the end of treatment were 15% of the control value. The levels of free fatty acids were decreased, whereas triglyceride levels were unaffected, indicating impaired fat metabolism. Daily urinary excretion of total carnitine was four to five times higher than controls after the first day of treatment, although the amounts of free carnitine and acetylcarnitine were decreased. The urinary acylcarnitines were isolated and characterized by gas chromatography/electron impact mass spectrometry and fast-atom bombardment mass spectrometry. Pivaloylcarnitine was the predominant urinary acylcarnitine; it represented greater than 96% of the increased excretion of total carnitine and 75-80% of the total conjugated pivalic acid. The renal clearance of acylcarnitines was comparable to that of creatinine, indicating no reabsorption of pivaloylcarnitine. These data suggest a detoxification function of carnitine for pivalic acid in humans.

Effect of etomoxiryl-CoA on different carnitine acyltransferases.

The effects of etomoxiryl-CoA on purified carnitine acyltransferases and on carnitine acyl-transferases of rat heart mitochondria and rat liver microsomes were determined. At nanomolar concentrations, the data agreed with that of other investigators who have shown that etomoxiryl-CoA must be binding to a high affinity site with specific inhibition of mitochondrial carnitine palmitoyltransferase (CPTo). Micromolar amounts of etomoxiryl-CoA inhibited both short- and long-chain carnitine acyltransferases. The concentrations of etomoxiryl-CoA required for 50% inhibition of the different carnitine acetyltransferases and microsomal and peroxisomal carnitine octanoyltransferase were in the low micromolar range. Mixed-type and uncompetitive inhibition kinetics were obtained, depending on the source of purified enzyme. When purified rat heart CPT was incubated with etomoxiryl-CoA, it increased the K0.5 and decreased the Hill coefficient for acyl-CoA. Both proteins and phospholipids of mitochondria and microsomes formed covalent adducts of [3H]etomoxir, with the predominant labeling in phospholipids. None of the purified enzymes formed covalent adducts when incubated with [3H]etomoxiryl-CoA, in contrast to intact mitochondria or microsomes. The major 3H-labeled protein for rat heart mitochondria had a molecular weight of 81,000 +/- 4000, and the major proteins from microsomes had a molecular weight of 51,000-57,000. Malonyl-CoA prevented most of the tritum incorporation into the 81,000 Da protein of mitochondria, but it had little effect on incorporation of tritiated etomoxir into the 51,000-57,000 Da proteins of microsomes. When 50 microM etomoxiryl-CoA was added to microsomes and to mitochondria that had been incubated with radioactive etomoxiryl-CoA, much of the radioactive etomoxir disappeared from the major microsomal proteins, but virtually none was displaced from the mitochondrial protein. Thus, at least two different types of covalent etomoxir complexes were formed. This pulse-chase experiment showed that the mitochondrial protein-etomoxir complex was not turned over, consistent with other data showing that etomoxir inhibited carnitine palmitoyltransferase. In contrast, the major protein-etomoxir complex in microsomes was turned over during the pulse-chase experiment.

Geographically-based cancer control: methods for targeting and evaluating the impact of screening interventions on defined populations.

Successful implementation of cancer control programs depends on efficient targeting to those at highest risk of developing and dying from the disease. This study presents a methodology for targeting cancer screening on the basis of population and disease variation among small geographic areas. Techniques for quantifying the impact of targeting on the predictive value of a positive test are demonstrated, using 329 New York City health areas. Age-truncated crude incidence, late-stage incidence and mortality rates for breast, cervix, and colorectal cancer are used, using site-specific truncation points relevant to the age groups appropriate for screening. Coefficient alpha was used to determine rate stability with 2, 3, 5 and 7 years of data. The stability of most small area rates was found to reach acceptable levels only with 5 and 7 years of data. Targeting into areas where breast cancer prevalence was high increased the expected predictive value of a positive test by as much as 50% when compared with areas of average prevalence. Geographic targeting will be most useful where between-area variability in prevalence is large and within-area variability is small. The implications of these results are discussed and future studies are suggested.