Pancreatic cancer and serum organochlorine levels.

Occupational exposure to p,p'-dichlorodiphenyltrichloroethane (DDT) has been associated with increased pancreatic cancer risk. We measured organochlorine levels in serum obtained at the study enrollment from 108 pancreatic cancer cases and 82 control subjects aged 32-85 years in the San Francisco Bay Area between 1996 and 1998. Cases were identified using rapid case-ascertainment methods; controls were frequency-matched to cases on age and sex via random digit dial and random sampling of Health Care Financing Administration lists. Serum organochlorine levels were adjusted for lipid content to account for variation in the lipid concentration in serum between subjects. Median concentrations of p,p'-dichlorodiphenyldichloroethylene (DDE, 1290 versus 1030 ng/g lipid; P = 0.05), polychlorinated biphenyls (PCBs; 330 versus 220 ng/g lipid; P<0.001), and transnonachlor (54 versus 28 ng/g lipid; P = 0.03) were significantly greater among cases than controls. A significant dose-response relationship was observed for total PCBs (P for trend <0.001). Subjects in the highest tertile of PCBs (> or =360 ng/g lipid) had an odds ratio (OR) of 4.2 [95% confidence interval (CI) = 1.8-9.4] compared to the lowest tertile. The OR of 2.1 for the highest level of p,p'-DDE (95% CI = 0.9-4.7) diminished (OR = 1.1; 95% CI = 0.4-2.8) when PCBs were included in the model. Because pancreatic cancer is characterized by cachexia, the impact of this on the serum organochlorine levels in cases is difficult to predict. One plausible effect of cachexia is bioconcentration of organochlorines in the diminished lipid pool, which would lead to a bias away from the null. To explore this, a sensitivity analysis was performed assuming a 10-40% bioconcentration of organochlorines in case samples. The OR associated with PCBs remained elevated under conditions of up to 25% bioconcentration.     

Racial variation in the use of do-not-resuscitate orders

OBJECTIVE: To compare the use of do-not-resuscitate (DNR) orders in African-American and white patients using a large, multisite, community-based sample. MEASUREMENTS: Our sample included 90,821 consecutive admissions to 30 hospitals in a large metropolitan region with six nonsurgical conditions from 1993 through 1995. Demographic and clinical data were abstracted from medical records. Admission severity of illness was measured using multivariate risk-adjustment models with excellent discrimination (receiver-operating characteristic curve areas, 0.82–0.88). Multiple logistic regression analysis was used to determine the independent association between race and use of DNR orders, adjusting for age, admission severity, and other covariates. MAIN RESULTS: In all patients, the rate of DNR orders was lower in African Americans than whites (9% vs 18%; p<.001). Rates of orders were also lower (p<.001) among African Americans in analyses stratified by age, gender, diagnosis, severity of illness, and in-hospital death. After adjusting for severity and other important covariates, the odds of a DNR order remained lower (p<.001) for African-Americans relative to whites for all diagnoses, ranging from 0.38 for obstructive airway disease to 0.71 for gastrointestinal hemorrhage. Results were similar in analyses limited to orders written by the first, second, or seventh hospital day. Finally, among patients with DNR orders, African Americans were less likely to have orders written on the first hospital day and more likely to have orders written on subsequent days. CONCLUSIONS: The use of DNR orders was substantially lower in African Americans than in whites, even after adjusting for severity of illness and other covariates. Identification of factors underlying such differences will improve our understanding of the degree to which expectations for care differ in African American and white patients. Dr. Rosenthal is a Research Associate, Health Services Research and Development Service, Department of Veterans Affairs, and was a recipient of a Picker/Commonwealth Scholar’s Award from the Commonwealth Fund when this work was conducted. Presented in part at the annual meeting of the Society of General Internal Medicine, Washington, DC, April 1997, and at the annual meeting of the Midwest Society of General Internal Medicine, Chicago, Ill., September 1997.     

塞来昔布在类风湿性关节炎中对甲氨喋呤的药代动力学影响

目的：确定塞来昔布对于经常服用稳定剂量甲氨喋呤（ＭＴＸ）治疗类风湿性关节炎（ＲＡ）患者的肾脏清除率和血浆药代动力学方面的影响。方法：选取１４例至少已服用ＭＴＸ３个月,且每个星期的剂量稳定在５－１５ｍｇ,有类风湿关节炎的成年妇女,随机给予塞来昔布（２００ｍｇ．ｂｉｄ）或安慰剂单盲治疗,每一阶段７,分二阶段交叉试验,研究ＭＴＸ的药代动力学和肾脏平均清除率。结果：当ＭＴＸ和塞来昔布或安慰剂合用时,ＭＴＸ     

Targeted ingrowth and glial relationships of olfactory receptor axons in the primary olfactory pathway of an insect

Olfactory receptor axons in many species terminate centrally in an array of distinct glomeruli that are thought to encode the molecular features of odors. Particular molecular attributes are detected by receptor neurons widely distributed over the sensory epithelium, but these neurons then project to a small number of glomeruli in the olfactory bulb. This raises perplexing questions about olfactory axon guidance, especially how axons sort by odor specificity and how they find their appropriate targets in the brain. Taking advantage of the relative cellular simplicity of the moth antennal system, we have examined receptor axons in normally developing animals and also in preparations in which the nerve was experimentally misrouted. Just before they enter the antennal lobe, receptor axons undergo a dramatic reorganization in a discrete zone filled with glial cells. Here they shed neighbor relationships and become associated with axons that have common targets and presumably share common odor specificies. Electron microscopy revealed that the growth cones of early arriving axons travel preferentially next to glial processes. The growth cones of receptor axons were relatively simple except as they entered newly forming glomeruli. Misrouted nerves turned and ran along the surface of the brain until they reached the region of the antennal lobe. In only 6% of cases did misrouted axons enter the brain ectopically, never forming glomeruli. Our results suggest that olfactory receptor axons are attracted to the antennal lobe by soluble or surface-bound cues and sort by odor specificity by using a mechanism that may involve glial cells. J. Comp. Neurol. 398:119–138, 1998. © 1998 Wiley-Liss, Inc.     

Asplenia syndrome in a child with a balanced reciprocal translocation of chromosomes 11 and 20 [46,XX,t(11;20)(q13.1;q13.13)]

We present a 6-year-old girl with a balanced 11;20 translocation [46,XX,t(11;20)(q13.1;q13.13)pat], asplenia, pulmonic stenosis, Hirschsprung disease, minor anomalies, and mental retardation. This case represents the second report of an individual with situs abnormalities and a balanced chromosome rearrangement involving a breakpoint at 11q13. Polymerase chain reaction (PCR) analysis of microsatellite markers excluded uniparental disomy for chromosomes 11 and 20. Segregation analysis of markers in the 11q13 region in the proposita and her phenotypically normal carrier sibs did not show a unique combination of maternal and paternal alleles in the patient. We discuss several possible explanations for the simultaneous occurrence of situs abnormalities and a balanced 11;20 translocation. These include (1) chance, (2) a further chromosome rearrangement in the patient, (3) gene disruption and random situs determination, and (4) gene disruption plus transmission of a recessive or imprinted allele from the mother. © 1996 Wiley-Liss, Inc.     

Recapture of GFP chromophore fluorescence in a protein host

When encapsulated by human serum albumin (HSA), certain derivatives of the green fluorescent protein (GFP) chromophore recover their fluorescence due to inhibition of torsional motion. These derivatives show remarkable sensitivity and selectivity as well as favorable spectroscopic properties toward HSA, thus providing selective probes for this and similar proteins and demonstrating the use of GFP chromophores as topological fluorophores.     

Personality heterogeneity in female adolescent inpatients with features of eating disorders

Objective

This study examined evidence for personality variability in adolescents with eating disorder features in light of previous evidence that personality variability in adult women with eating disorder symptoms carries important clinical implications.

Method

Millon Adolescent Clinical Inventory personality data from adolescent girls with disturbed eating who were psychiatrically hospitalized were cluster analyzed, and resulting groups were compared in eating and comorbid psychopathology.

Results

Three subgroups were identified among the 153 patients with eating disorder features: high functioning, internalizing, and externalizing. The internalizing group was marked by eating-related and mood dysfunction; the externalizing group by elevated eating and mood psychopathology as well as impulsivity, aggression, and substance use; and the high-functioning group by lower levels of psychopathology and relatively high self-esteem.

Conclusions

These findings converge with previous research using different personality models in adult samples and highlight the clinical use of considering personality heterogeneity among adolescent and adult women with disturbed eating.     

Physical Activity Disparities Between US-born and Immigrant Children by Maternal Region of Origin

We examined and compared patterns in physical activity participation for children of US-born and immigrant mothers from seven world geographic regions, and tested whether the physical activity differences were attenuated by socioeconomic status or maternal language proficiency. Using the Early Childhood Longitudinal Study-Kindergarten data (N = 18,850) we utilized logistic regression to predict adequate vigorous physical activity and participation in group and individual sports for kindergarten children. US-born children of US-born parents have significantly higher rates of physical activity compared to immigrant children. Children of Mexican, Southeast Asian, and Caribbean immigrants were especially unlikely to participate in sports. These disparities were not significantly attenuated by socioeconomic status, but accounting for language proficiency reduced some differences between the US-born and immigrant children, particularly for group sports participation. Researchers interested in improving the physical activity patterns of second-generation children should consider the relevance of language barriers in promoting healthy living.     

Familial eosinophilic cellulitis, dysmorphic habitus, and mental retardation

Background: Eosinophilic cellulitis is a polymorphous, chronic disease characterized by eosinophil infiltration and granulomatous inflammation. Objective: Our purpose was to describe the clinical, histologic, and immunohistologic findings in three family members who have had eosinophilic cellulitis since childhood associated with mental retardation and abnormal body habitus. Methods: Family members were evaluated. Multiple skin biopsy specimens were obtained and examined after hematoxylin-and-eosin staining, by immunofluorescence and by electron microscopy. Blood specimens were analyzed by immunoassays for eosinophil granule proteins and eosinophil active cytokines. Results: Three short-statured, mentally retarded family members with abnormal body habitus in at least two generations had recurrent eosinophilic cellulitis. Peripheral blood and bone marrow eosinophilia was present. Plasma eosinophil granule major basic protein and eosinophil-derived neurotoxin levels were elevated with normal plasma eosinophil cationic protein levels. Eosinophil survival in culture was increased by patients’ plasma and was blocked with monoclonal interleukin-5 antibody. The level of plasma interleukin-5 was elevated. Lesional skin biopsy specimens showed massive staining for three eosinophil granule proteins. Electron microscopy showed eosinophil disruption. Conclusion: Eosinophilic cellulitis, mental retardation, and abnormal body habitus were likely inherited as a dominant syndrome in this family in which eosinophil involvement was striking. (J Am Acad Dermatol 1998;38:919-28.)     

Differential increase of hepatic peroxisomal,mitochondrial and microsomal carnitine acyltransferases in clofibrate-fed rats

Hepatic peroxisomes, mitochondria and microsomes from control and clofibrate-treated animals were separated by isopycnic sucrose gradient centrifugation and the carnitine acyltransferase system studied in each of these organelles. Clofibrate treatment produced a 13-fold increase in the total activity of carnitine acetyltransferase and a 5-fold increase in carnitine octanoyl- and palmitoyl-transferase activities. The specific activities of the transferases in all three subcellular locations increased, but to different extents. Peroxisomal and microsomal carnitine acetyltransferases doubled in specific activity; the mitochondrial enzyme increased 10-fold. Peroxisomal, mitochondrial and microsomal carnitine octanoyltransferases all increased 3-fold in specific activity. Carnitine palmitoyltransferase, which is found only in mitochondria, increased 3-fold in specific activity. These differential increases changed the per cent distribution of total carnitine acetyltransferase from 50 per cent in the mitochondria of control livers to 90 per cent in treated livers. Peroxisomes from clofibrate-treated livers had a consistently greater isopycnic density in sucrose gradients. Total catalase activity increased 2-fold upon treatment and a greater percentage of it was found in the paniculate fractions. The specific activity of peroxisomal catalase and urate oxidase remained the same as in controls. Carnitine acetyl- and octanoyltransferases are the first reported enzymes whose peroxisomal specific activity increases with clofibrate treatment. Preliminary results of treatment with another membrane-inducing drug, phenobarbital, indicated no change in peroxisomal density, catalase distribution and activity, and no effect on the specific activities of the peroxisomal, mitochondrial and microsomal carnitine acyltransferases.