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Biomedical subjects

J Kerner

Publications and source records attributed to J Kerner.

At least 37 records · Page 2Linked to original sources

Barriers to follow-up of abnormal screening mammograms among low-income minority women. Cancer Control Center of Harlem.

OBJECTIVE: To describe factors related to compliance diagnostic follow-up among minority women of low socioeconomic status with abnormal screening mammograms. METHODS: A retrospective cross-sectional survey using a structured telephone interview. Three cancer screening clinics at an urban inner-city public hospital. All women with abnormal screening mammograms between September 1990 and January 1992 were eligible; women were interviewed in August 1992. Abnormal mammograms were those requiring specific, non-routine clinical follow-up; non-compliance was defined as delayed follow-up (four to six months after the date of the mammogram), or no follow-up at the time of interview (more than 6 months after abnormal). RESULTS: Sixty-two of 442 screened women had abnormal results; the overall rate of non-compliance with follow-up was 50%. Among the 42 (68%) women who agreed to be interviewed, non-compliers were less likely to state that they had been told to receive follow-up than compliers (65% versus 100%; p = 0.008). Non-compliant women were less likely to have suspicious mammography interpretations (p = 0.05), and more likely to report barriers to follow-up, such as cost of lost wages and medical care, system barriers, or fears, than compliant women (61.9% versus 9%, p = 0.01). There were no differences between the two groups for age, education, insurance, source of care, family history, knowledge or attitudes. CONCLUSIONS: These preliminary results suggest that follow-up of low income, minority women with abnormal screening mammograms could be enhanced by improved communication of results. Future studies should extend these findings with larger samples and in other settings and populations.

Adolescent↗

The late-stage diagnosis of colorectal cancer: demographic and socioeconomic factors.

OBJECTIVES: This study described factors related to colorectal cancer stage at diagnosis. METHODS: Logistic regression analyses were used on data from the New York State Tumor Registry and US Census area-level social class indicators. RESULTS: After the effects of other predictors were controlled for, the odds of late-stage cancer increased as age decreased; women and African Americans were significantly more likely to have late stage than men and Whites; and individuals living in areas of low socioeconomic status (SES) were significantly more likely to be diagnosed at late stage than those living in higher SES areas. Stratified analyses showed that living in a low SES area was the most important determinant of stage for all age, race, gender and source-of-care groups. CONCLUSIONS: While all populations would benefit from the systematic use of screening socioeconomically disadvantaged groups may also benefit from targeted screening.

Adult↗

Validation of an acculturation measure for Hispanic adolescents.

Based on the continuing growth and youthfulness of the Hispanic population in the United States, valid cultural measures are needed for Hispanic adolescents. Hispanics living in this country experience acculturation or cultural change during their exposure to American culture. A matched sample of 994 Hispanic students and their parents completed acculturation measures. Scores on a 10-item acculturation scale completed by the adolescents' parents correlated significantly .49 with a single-item rating, a measure of acculturation by adolescents. This finding supports construct validity for a measure of language use as an index of linguistic acculturation for Hispanic adolescents.

Acculturation↗

Intravenous amitriptyline in pediatrics.

Oral amitriptyline has been used as an analgesic in a wide range of pain settings. Despite long-term availability of a parenteral form, the few reports about this formulation have been limited to pharmacokinetic studies in normal volunteers, trials in depressed patients, and analyses of electroencephalogram (EEG) activation. We retrospectively reviewed our experience using intravenous (IV) amitriptyline at Children's Hospital, Boston and at Children's Hospital at Stanford. Eight children (aged 5-16.6 years), who were unable to tolerate medications by the oral route, received IV amitriptyline for a variety of indications, including neuropathic pain, depression, sleep disturbance, and as an adjuvant agent for opioid analgesia. One patient experienced an extrapyramidal reaction temporally related to the administration of IV amitriptyline, which was successfully managed with diphenhydramine. Further prospective, controlled studies are needed to further assess the safety, efficacy and tolerability of this novel use of amitriptyline.

Adolescent↗

Impaired gut lipid absorptive capacity after trauma-hemorrhage and resuscitation.

Although the barrier function of the intestinal mucosa is impaired after hemorrhage, it remains unclear whether this is associated with a deficit in mucosal function. The aim of this study, therefore, was to determine whether trauma-hemorrhage affects the in vivo lipid absorptive capacity of the gut and, if so, to characterize the uptake process of free fatty acids in isolated enterocytes. To study this, rats were anesthetized, a laparotomy was performed (i.e., trauma was induced), and various blood vessels were cannulated. For in vivo lipid absorption, the main intestinal lymph vessel was cannulated and a jejunostomy feeding tube was inserted. The animals were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of shed blood volume was returned in the form of Ringer lactate. They were then resuscitated with four times the volume of maximal bleed out with Ringer lactate. The in vivo and in vitro lipid absorptive capacities were assessed by measuring lymph triglyceride output after a fat load and by determining the linoleic acid uptake rates on isolated enterocytes, respectively. The results show that the in vivo lipid absorption capacity of the gut is severely depressed after trauma-hemorrhage and resuscitation. Similarly, in enterocytes isolated from hemorrhaged rats, fatty acid uptake capacity, as reflected by the decreased maximal uptake rates, was significantly reduced: 1.2 +/- 0.2 and 2.6 +/- 0.6 nmol.min-1 x 10(6) cells-1 for hemorrhaged and sham, respectively. Thus gut lipid absorptive function is depressed after trauma-hemorrhage and resuscitation, which is at least partially due to the depressed uptake mechanism of the enterocyte.

Animals↗

Impact of access and social context on breast cancer stage at diagnosis.

This study examined the impact of individual demographic characteristics (age, race/ethnicity, and type of reporting hospital), together with measures of social context, including area of residence socioeconomic status (SES), change in SES, and access to screening (area mammography capacity), on breast cancer stage at diagnosis among New York City residents diagnosed between 1980 and 1985. Three logistic regression models evaluated the impact of individual variables, social context variables, and both classes of variables combined on the outcome of having late-stage (regional or distant) compared to early-stage (local) cancer. The logistic regression models indicated that women aged 50 to 64 years were independently more likely to have late-stage cancer than those younger or older. Controlling for individual and social context variables, African American women were 25 percent more likely than White women to have late-stage breast cancer (p < 0.0001); higher odds seen in the individual model for Hispanic women disappeared after controlling for area SES. In the combined model, women diagnosed from public hospitals were 44 percent more likely to have late-stage disease than those diagnosed in nonpublic settings (p < 0.0001). In both the social context and combined models, area mammography capacity was a significant independent predictor of stage (p = 0.016); area-level SES, but not change in SES, was independently related to late-stage disease (p = 0.002). These data suggest that breast cancer control activities should more actively ensure adequate access to screening, particularly for minorities, populations living in socioeconomically disadvantaged areas, and those cared for in the public sector.

Adult↗

Characterization of the malonyl-CoA-sensitive carnitine palmitoyltransferase (CPTo) of a rat heart mitochondrial particle. Evidence that the catalytic unit is CPTi.

A post 30,000 x g particulate fraction was isolated from rat heart. This mixed membrane fraction is enriched in a carnitine palmitoyltransferase which is sensitive to both malonyl-CoA and etomoxiryl-CoA at concentrations that inhibit the malonyl-CoA-sensitive carnitine palmitoyltransferase (CPTo/CPT-I) of intact mitochondria. Tritiated etomoxiryl-CoA labels two proteins with the same molecular weight as the labeled proteins from rat heart mitochondria. Malonyl-CoA-sensitive carnitine palmitoyltransferase in the particulate fraction is stable to freeze-thawing, and the activity is not latent. These data show that the carnitine palmitoyltransferase associated with this particle is CPTo/CPT-I. Positive Western blots were obtained, with the particle using anti-CPTi/CPT-II at a molecular weight identical with the CPT1/CPT-II purified from rat heart mitochondria. Catalytic activity was purified to near homogeneity in approximately 40% yield. The purified protein has a molecular weight identical with CPTi/CPT-II, it cross-reacts with antibody against CPTi/CPT-II, it is not inhibited by malonyl-CoA or etomoxiryl-CoA, and mass spectral analyses of the tryptic peptides give the same molecular masses as CPTi/CPT-II, and, when mixed with equal amounts of CPTi/CPT-II, one uniform spot is found by two-dimensional electrophoresis. These data indicate that the catalytic subunit of CPTo/CPT-I is the same as CPTi/CPT-II. The average inhibition of the CPT of frozen-thawed particles is 71% by 50 nM etomoxiryl-CoA and 62% by 50 nM malonyl-CoA. The inhibitor sensitivity, but not the catalytic activity, is lost by solubilization in 1% Triton X-114; removal of Triton X-114 using Extracti-Gel D restores etomoxiryl-CoA and malonyl-CoA sensitivity (both 50 nM) of CPT to an average of 77 and 48%, respectively. Consistent with previous reports, these results show that CPTo/CPT-I is NOT inactivated by detergents, rather detergents both desensitize it to malonyl-CoA and alter its Vmax. These data show the assumption that CPTo/CPT-I is inactivated by detergents is untenable.

Amino Acid Sequence↗

Rapid determination of amino acids by high-performance liquid chromatography: release of amino acids by perfused rat liver.

Perfused rat liver can be considered as one of the most suitable ex vivo models for studies of liver metabolism. To assess the possible effect of L-carnitine and some of its acyl esters on proteolysis in the rat liver, the amino acid derivatization and high-performance liquid chromatographic separation of Tapuhi et al. [Anal. Biochem., 115 (1981) 123] was modified.

Amino Acids↗

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.

Adenosine Triphosphate↗

Smoking prevention among urban minority youth: assessing effects on outcome and mediating variables.

We tested the effectiveness of a social resistance/competence enhancement approach to smoking prevention among predominantly Hispanic seventh graders (N = 3,153) from 47 New York City schools. After blocking on school type (public and parochial) and ethnic composition (percent Hispanic), schools were randomly assigned either to receive the 15-session prevention program or to serve as no-contact controls. Using the school as the unit of analysis, significant program effects were found for cigarette smoking, normative expectations concerning peer and adult smoking, smoking prevalence knowledge, social acceptability knowledge, and knowledge of smoking consequences. Using structural modeling techniques, a significant relation was found between the normative expectation and knowledge variables affected by the intervention and posttest smoking, suggesting that changes on these variables mediated the impact of the intervention on cigarette smoking. This study extends the results of previous prevention research and demonstrates the generalizability of this approach to predominantly Hispanic urban minority students.

Adolescent↗

Determinants of late stage diagnosis of breast and cervical cancer: the impact of age, race, social class, and hospital type.

Previous studies of the relationship between cancer stage, age, and race have not controlled for social class and health care setting. Logistic regression analyses, using information from the New York State Tumor Registry and area-level social class indicators, demonstrated that, in New York City, older Black, lower class women in public hospitals were 3.75 and 2.54 times more likely to have late stage breast or cervical cancer, respectively, than were younger White, high social class women in non-public hospitals.

Adult↗

Isolation of a malonyl-CoA-sensitive CPT/beta-oxidation enzyme complex from heart mitochondria.

The goal of this study was to establish conditions for solubilization and characterization of CPTo, the malonyl-CoA sensitive form of mitochondrial carnitine palmitoyltransferase. CPTo of heart mitochondria is soluble in 1% octyl glucoside with retention of malonyl-CoA sensitivity. The degree of malonyl-CoA sensitivity is dependent on both the concentration of octyl glucoside and the presence of salt (KCl). In mannitol-sucrose, 0.5-1% octyl glucoside solubilizes CPTo without loss of malonyl-CoA sensitivity; however, either increasing the detergent concentration or addition of KCl promotes loss of malonyl-CoA sensitivity. The immunoglobulin fraction from immune serum obtained from rabbits immunized with the malonyl-CoA-insensitive form of CPT (CPTi) purified from beef heart mitochondria was used for preparation of an affinity column. The antibody column retained both malonyl-CoA-sensitive and -insensitive CPT activity without apparent selectivity. In addition to CPT, several other major protein bands were detected when the antibody column eluates were subjected to SDS-PAGE; however, native gel electrophoresis gives a large, high molecular weight, diffuse band. After elution of the antibody-CPT column with salt, a 68,000-Da protein is retained by the column. The retained protein contains the CPT activity, but it is not inhibited by malonyl-CoA. Thus, salt elution separates catalysis from inhibition. When the salt eluate is subjected to affinity chromatography using agarose-CoA, two protein peaks are obtained; both bind malonyl-CoA. One of the two fractions contains beta-hydroxyacyl-CoA dehydrogenase, beta-ketothiolase, and crotonase activity. These data show that octyl glucoside solubilized CPTo and CPTi are associated with a complex that contains beta-oxidation enzymes.

Acyl Coenzyme A↗

Differential excretion of xenobiotic acyl-esters of carnitine due to administration of pivampicillin and valproate.

The fate of supplemental carnitine was studied in human subjects treated with drugs known to cause carnitine deficiency. Six children were treated with pivampicillin and equimolar L-carnitine for 7 days. On the last day of treatment, the plasma levels of total and free carnitine were decreased, but acylcarnitine levels were increased. A 12-fold increase in urinary excretion of acylcarnitines was found; it increased from 188.5 +/- 82.7 to 2218.4 +/- 484.1 mumole/day, and 84% was pivaloylcarnitine. Free carnitine excretion was reduced. Ten epileptic children on chronic valproate treatment received equimolar carnitine for a 2-week period. Plasma carnitine levels were elevated on the last day of treatment. A 3.4-fold increase in urinary acylcarnitines was found, but most of the excreted carnitines were free (64.5-fold increases). These data show that pivalate is readily converted to carnitine esters, in contrast to the limited conversion of valproate to acylcarnitines in humans.

Adolescent↗

L-carnitine replacement therapy in chronic valproate treatment.

Ten epileptic children with chronic valproic acid (VPA) treatment were given L-carnitine for 14 days. As compared to age and sex matched control subjects the carnitine status of the VPA treated children showed carnitine insufficiency prior to the carnitine administration with lower total and free carnitine in plasma and in urine. In response to the extra intake the plasma free and esterified carnitines increased 1.7-fold. The daily excreted amount of esterified carnitines increased 6.5-fold (1.55 +/- 0.23 vs 10.1 +/- 1.68 mumol/kg/day, means +/- SEM, p less than 0.005) showing that a considerable part of the administered carnitine participated in the elimination of acyl groups from the body. The depressed level of beta-hydroxybutyrate in the plasma (31.8 +/- 7.42 vs controls 118.0 +/- 16.0 mumol/l, means +/- SEM, p less than 0.005) remained unaffected by the carnitine administration (29.7 +/- 7.06 mumol/l) suggesting that the hypoketonemia is not a direct consequence of the carnitine insufficiency. No differences were observed in the plasma level of free fatty acids, triglycerides and in insulin: glucagon ratios between the VPA treated and control subjects, suggesting that lipolysis of fats and the hepatic hormonal control mediated by these hormones are not the sites at which VPA causes reduced fasting ketogenesis. The plasma level of VPA and the seizure control remained unaffected by carnitine treatment.

Adolescent↗

Ethnicity and psychosocial factors in alcohol and tobacco use in adolescence.

Research on ethnic group differences has suggested that (a) adolescents from various groups differ on a number of dimensions that have been related to risk for substance use initiation, and (b) adolescents of different groups choose different substances. However, there is little consensus regarding the reasons for such differences. There is an especially high rate of alcohol use among Hispanic adolescents, and Hispanics are at high risk for alcohol abuse. In light of ethnic group differences in both substance use and the precursors of substance use in adolescence, this study examined differences among black, Anglo, Puerto Rican, and Dominican adolescents in the relation between cigarette and alcohol use and psychosocial functioning. Comparisons between the Puerto Rican and Dominican subjects were of special interest due to preexisting differences between these groups that may be attributed to acculturation. Results provided evidence of the importance of acculturation in modifying psychosocial vulnerability, especially for alcohol use, with the Dominican group at highest risk.

Acculturation↗

Carnitine ester excretion in pediatric patients receiving parenteral nutrition.

Carnitine plasma concentrations and the excretion of carnitine and individual carnitine esters were determined in 25 children and adolescents with gastrointestinal diseases receiving carnitine-free parenteral nutrition for at least 1 mo using radiochemical and radioisotopic exchange HPLC methods. Children less than 12-y-old usually had carnitine plasma concentrations less than -2 SD from the normal mean for age, whereas patients greater than 12-y-old had carnitine plasma concentrations within the normal range. Age was the only variable to correlate significantly with plasma carnitine concentrations during parenteral nutrition. Free carnitine (FC) excretion was closely correlated with plasma FC concentrations and minimal at values less than 25 mumols/L. The excretion of FC and short-chain acylcarnitines was reduced by an order of magnitude in younger compared with older patients and controls, but the excretion of "other" acylcarnitines was less affected. Some of the latter were tentatively identified using gas-liquid chromatographic and mass spectroscopic techniques as unsaturated and/or branched medium-chain carnitine esters with a carbon chain of C8-C10. The results suggest that FC and short-chain acylcarnitine are conserved by the kidney in nutritional carnitine deficiency but that there may be an obligatory renal excretion of other carnitine esters that contributes to the development of hypocarnitinemia in the younger age group.

Absorption↗

Feeding preterm infants with L-carnitine supplemented formula.

A total of 29 preterm infants maintained on mixed enteral nutrition (50% pooled human milk, 50% formula daily) were studied over a 15 days period. 16 of them received L-carnitine supplemented formula during the first seven consecutive days (600 nmol/ml, as added supplement), 13 infants served as controls. In response to enhanced dietary intake, the plasma levels and urinary excretion rates of carnitines were increased by the 7th day of study. The plasma carnitines then returned to the initial values, whilst the urinary excretion remained elevated at the 14th day of study. The elevated daily urinary excretion of carnitines was accompanied by increased clearance and decreased relative reabsorption rates in the supplemented group. In the control group the plasma carnitine levels remained unchanged throughout the observations, while the daily excretion of free carnitine decreased by the end of the study. In the supplemented group statistically significant decrease was found in the daily excreted ammonia and urea with a decrease of plasma alanine and glutamine levels by the 7th day of study. The plasma levels of beta-hydroxybutyrate, glucose and creatinine remained unchanged in both groups.

Absorption↗