A nested case-control study of non-Hodgkin lymphoma and serum organochlorine residues

BACKGROUND: The steady worldwide increase in the incidence of non-Hodgkin lymphoma during the past few decades remains mostly unexplained. Several studies suggest that there may be an association between the agricultural use of the organochlorine 1,1,1-trichloro-2,2'bis(p-chlorophenyl)ethane (DDT) and increased risk of non-Hodgkin lymphoma. We have investigated the association between risk of non-Hodgkin lymphoma and body burden of selected organochlorines in the general population in a nested case-control study. METHODS: We measured prediagnostic serum concentrations of DDT, its metabolites, and other organochlorines, including polychlorinated biphenyls (PCBs), in 74 cases of non-Hodgkin lymphoma and 147 matched controls identified from a prospective cohort of 25,802 adults, established in 1974 in Washington County, Maryland, USA. We report results for total lipid-corrected serum concentrations of DDT and total PCBs. FINDINGS: There was a strong dose-response relation between quartiles of total lipid-corrected serum PCB concentrations and risk of non-Hodgkin lymphoma overall (odds ratios by quartile: 1.0; 1.3 [95% CI 0.5-3.3]; 2.8 [1.1-7.6]); and 4.5 [1.7-12.0]; p for trend = 0.0008) and separately in men and in women. There was also evidence suggesting that seropositivity for the Epstein-Barr virus early antigen potentiated the effects of serum PCBs. By contrast, total lipid-corrected serum concentrations of DDT were not associated with risk of non-Hodgkin lymphoma. INTERPRETATION: These results should be regarded as hypothesis-generating. Before causal inferences can be made about exposure to PCBs and increased risk of non-Hodgkin lymphoma, our findings require replication and the biological plausibility of the association needs further investigation.     

Thrombospondin-1 and its CSVTCG-specific receptor in wound healing and cancer

Accumulation of mutant p53 protein occurs frequently in human malignancies, including 40-60% of non-small cell lung carcinomas. The implications of such p53 over-expression, usually assessed by immunohistochemical techniques, for the prognosis of lung cancer patients remain undetermined. In this study, we used a time-resolved immunofluorometric assay to measure p53 protein concentrations in extracts prepared from 86 primary non-small cell lung tumours and examined the associations between p53 protein levels (corrected for total protein) and other clinico-pathologic variables, including post-surgical disease-free and overall survival. Contingency tables analysed by chi2 tests revealed no significant relationships between p53 status, defined by a median cut-off point, and patient gender, age, disease stage, histologic grade and type, lymph node extension, smoking history and administration of adjuvant chemotherapy or radiation. However, multivariate Cox proportional hazard regression analysis demonstrated a dose-response relationship between p53 concentration, expressed as a 4-level, quartile-divided variable, and increased risk of relapse (p = 0.010) and death (p = 0.016). Patients whose tumours contained p53 concentrations exceeding the median value had over 3-fold higher risk of relapse (p = 0.002) and death (p = 0.007) than those whose tumours had lower p53 concentrations. We also provide evidence suggesting that the impact of p53 on survival is greater in patients with squamous cell carcinoma than in those with adenocarcinoma. Although the latter finding needs confirmation, our results suggest that application of an immunoassay of p53 protein on non-small cell lung tumour extracts may identify patients at increased risk of unfavourable outcome.     

Knowledge and attitudes among California dental care providers regarding child abuse and neglect

Combination chemotherapy with paclitaxel plus a platinum compound (carboplatin or cisplatin) is the current regimen of choice for the treatment of advanced epithelial ovarian cancer. The two most widely used combinations are paclitaxel (135 mg/m2, 24-hour infusion) plus cisplatin (75 mg/m2) or paclitaxel (175 mg/m2, 3-hour infusion) plus carboplating dosed to an area under curve of 7.5. Randomized trials are in progress comparing these two regimens. Numerous other clinical issues remain regarding how to maximize the effectiveness of this therapy, including dose and schedule, duration of treatment, route of administration, and incorporation of other agents with novel mechanisms of cytotoxicity. New agents currently undergoing evolution as part of novel induction regimens have been shown to have significant activity in recurrent ovarian cancer and include topotecan, gemcitabine, oral etoposide, and encapsulated doxorubicin.     

Are (some) reports of attitude strength context dependent?

Assessed the impact of subjective experiences on judgment of attitude strength. 60 undergraduate Ss (median age 19 yrs) generated either 3 or 7 arguments that either supported. (for some Ss) or countered (for other Ss) their attitude toward doctor-assisted suicide, and subsequently indicated the strength of their attitude. Ss reported that their attitude was more important, intense, and certain after having generated 3 rather than 7 pro-attitudinal (or 7 rather than 3 counter attitudinal) arguments, suggesting that attitude strength is not always a stable feature of an attitude. Implications for models of attitude strength are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ethylene glycol ethers and risks of spontaneous abortion and subfertility

Potential reproductive effects from occupational exposures to ethylene glycol ethers (EGE) are of concern since these organic solvents have been used widely in industry, and their reproductive toxicity has been well documented in animal studies. For determination of whether occupational exposure to EGE was associated with increased risks of spontaneous abortion and subfertility (i.e., taking more than 1 year of unprotected intercourse to conceive), a retrospective cohort study was conducted among workers at two semiconductor manufacturing plants in the eastern United States in 1980-1989 as part of a larger evaluation of reproductive health. Reproductive and occupational histories were obtained from interviews of semiconductor manufacturing workers and spouses. Assessment of potential exposure to mixtures containing EGE (none, low, medium, and high) was based on reported processes and company records. There were 1,150 pregnancies to semiconductor manufacturers, 561 to female employees and 589 to wives of male employees. Among female manufacturers, potential exposure to mixtures containing EGE was associated with increased risks of spontaneous abortion (relative risk in the high exposure group = 2.8; 95% confidence interval (CI) 1.4-5.6) and subfertility (odds ratio in the high exposure group = 4.6; 95% CI 1.6-13.3). Both of these risks exhibited a dose-response relation with potential EGE exposure (p for trend = 0.02). Among spouses of male manufacturers potentially exposed to mixtures containing EGE, there was no increased risk of spontaneous abortion, but there was a nonsignificant increased risk of subfertility (odds ratio in the high exposure group = 1.7; 95% CI 0.7-4.3).     

Rapid desensitization determines the pharmacology of glutamate neurotoxicity

Glutamate (Glu), the major excitatory neurotransmitter in the nervous system, is toxic to neurons when it accumulates at high concentrations in the extracellular space. Even though Glu is a mixed agonist, capable of activating N-methyl-D-aspartate (NMDA) receptors and non-NMDA receptors, in many preparations Glu neurotoxicity is prevented by selective blockade of NMDA receptors. In cultures of hippocampal neurons, treatment with 500 microM Glu for 30 min killed more than 90% of the neurons. The simultaneous addition of the selective NMDA agonist methyl-10,11-dihydro-5-H-dibenzocyclo-hepten-5,10-imine (MK-801) reduced the cell loss to less than 30%. However, when Glu was combined with either diazoxide or cyclothiazide, two thiazides which dramatically diminish rapid Glu desensitization, MK-801 was no longer very protective and neuronal loss exceeded 80%. However, the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), in combination with MK-801, was able to prevent most Glu neurotoxicity in the presence of these thiazides. These experiments show that there are circumstances under which Glu neurotoxicity is produced by overactivation of non-NMDA receptors. Our observations offer a possible explanation for the recent finding that blockade of non-NMDA receptors is much more beneficial than NMDA receptor blockade in protecting the brain in some in vivo models of global ischemia.     

Adiabatic slice-selective excitation for surface coils

A novel RF pulse designed to perform a diabatic slice-selective excitation for surface coils (ASSESS) is proposed in which Bzero gradient is modulated in concert with RF frequency modulation. Within the selected slice, the principles of BIR4 pulses are employed to obtain well-defined, pure-phase and self-refocused spin rotation of arbitrary flip angles despite the presence of high B1 inhomogeneity produced by surface coils. Outside the slice, advantage is taken of the B1 field to dephase equilibrium magnetization to achieve slice selection or outer-volume suppression. This scheme should be useful for many localization techniques. Quaternion analysis of the overall propagator of the proposed pulse and numerical simulations using Bloch equations are performed. The pulse is tested experimentally on a phantom sample.     

Equilibration of pancratic digestive enzymes across zymogen granule membranes

Zymogen granules isolated from the rat pancreas released digestive enzyms in response to lowering the enzyme concentration of the medium in which the granules were suspended, and reabsorbed enzyme when the enzyme concentration of the medium was increased. The evidence suggests that the distribution of digestive enzyme between zymogen granule and medium is the result of an equilibrium process. This equilibrium is apparently expressed across the granule membrane since the disruption of the membrane barrier eliminated the delay in establishing new equilibrium between the bound and free enzyme. The release of enzyme was continuous (equilibration did not occur) when the suspending medium was continuously filtered, thereby maintaining a constant state of disequilibrium between intragranular enzyme and enzyme in the medium. The data suggest the following: (1) that digestive enzyme passes through the intact granule membrane bidirectionally, and (2) that there is a free cytoplasmic pool of digestive enzyme in intact cells which is in equilibrium with the enzyme content of the zymogen granule.     

Sex, birth order, and maternal age characteristics of infants with congenital heart defects

The records of the New England Regional Infant Cardiac Program, a service program covering all of New England, provide a useful source of information about the characteristics of children born with congenital heart defects. Data were analyzed on more than 2000 children born in New England who were diagnosed with a congenital heart defect before the first birthday. Children with arterio-venous fistula, aortic stenosis, transposition of the great arteries or hypoplastic left ventricle were predominantly male; children with persistent ductus arteriosus and endocardial cushion defect were predominantly female. Positive trends in risk with increasing birth order were present for pulmonic stenosis and transposition of the great arteries, and a negative trend was seen for persistent ductus arteriosus. What evidence there was for associations with maternal age was greatly reduced after controlling for confounding by birth order.