The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies

The objective of this study was to examine the effects of the intakeof dietary fat upon colorectal cancer risk in a combined analysis of datafrom 13 case-control studies previously conducted in populations withdiffering colorectal cancer rates and dietary practices. Original datarecords for 5,287 cases of colorectal cancer and 10,470 controls werecombined. Logistic regression analysis was used to estimate odds ratios (OR)for intakes of total energy, total fat and its components, and cholesterol.Positive associations with energy intake were observed for 11 of the 13studies. However, there was little, if any, evidence of anyenergy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01,1.02, and 0.92 for quintiles of residuals of total fat intake (P trend =0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (Ptrend = 0.39). The analysis suggests that, among these case-control studies,there is no energy-independent association between dietary fat intake andrisk of colorectal cancer. It also suggests that simple substitution of fatby other sources of calories is unlikely to reduce meaningfully the risk ofcolorectal cancer.     

On Developing Self-concepts: A Controlled Study of Children and Adolescents with Autism

This study employed the self-understanding interview of Damon and Hart (1988) to assess the self-concepts of two groups of children and adolescents: a group of individuals with autism and a group of nonautistic mentally retarded individuals who were matched for age and for verbal ability. On the basis of an hypothesis concerning the interpersonal origins of social and psychological self-concepts (Hobson, 1990; Neisser, 1988), it was predicted that the participants with autism would show a relative dearth of such concepts in their talk about themselves. In accordance with our predictions, there was a significant group difference in the number and quality of statements that fell into the social category of self-concept; contrary to our predictions, however, there was no group difference in the number of statements that fell into the psychological category. In addition, although there were not significant group differences in the overall production of verbally expressed concepts concerning self-attributes of a physical, active, or psychological kind, even within these categories individuals with autism made fewer references to social interactions or qualities. These results are discussed with regard to theories of self-concept development in typically developing as well as autistic and mentally retarded individuals, and with reference to the limitations of interpersonal understanding ("theory of mind") in people with autism.     

Implications of Liver Cirrhosis in Pregnancy

Summary: We present the case of a pregnant woman with alcohol-induced liver cirrhosis and a discussion of the clinically relevant issues of cirrhosis in pregnancy.     

The case-case-control study design: addressing the limitations of risk factor studies for antimicrobial resistance.

OBJECTIVE: There are significant limitations of the standard case-control study design for identifying risk factors for resistant organisms. The objective of this study was to develop a study design to overcome these limitations. DESIGN: Theoretical analysis of different types of study designs that can be used in risk factor studies for resistant organisms. RESULTS: We developed the case-case-control study design, which uses two separate case-control analyses within a single study. The first analysis compares patients infected with resistant bacteria (resistant cases) with control-patients without infection caused by the target organism, who are therefore representative of the source population; and the second analysis compares patients infected with the susceptible phenotype of the target organism (susceptible cases) with the same control-patients without infection caused by the target organism. These two analyses provide risk models for (1) isolation of the resistant phenotype of the target organism as compared with the source population and (2) isolation of the susceptible phenotype of the organism as compared with the source population. When these two risk models are compared and contrasted, risk factors specifically associated with isolation of the resistant phenotype can be identified. CONCLUSIONS: The case-case-control study design is an effective method for identifying risk factors for antimicrobial-resistant pathogens. Although the case-case-control study design has limitations, it is, in our opinion, more informative and less flawed than the standard case-control study design.     

Pneumocephalus in neonatal meningitis: diffuse, necrotizing meningo-encephalitis in Citrobacter meningitis presenting with pneumatosis oculi and pneumocephalus.

OBJECTIVE/PATIENT: Gas-containing encephalitis is rarely associated with neonatal meningitis. We report a case of a 19-day-old baby who presented with a rapid onset of septic shock complicated by progressively increasing gas accumulation within the brain and anterior chamber of the eye. We describe the evolution of the clinical picture and the management. INTERVENTIONS: Ventilatory support, fluid resuscitation, and continuous venovenous hemofiltration were provided in view of multiple system failure. Despite effective antibiotic therapy and supportive management, the patient died with worsening accumulation of gas within the brain, resulting in brainstem death. RESULTS: Computed tomographic images were characteristic of diffuse necrotizing meningo-encephalitis. Postmortem examination showed friable brain tissue with venous infarction and extensive gas accumulation. Citrobacter koseri was identified from the blood and cerebrospinal fluid cultures. CONCLUSION: This case re-emphasises the importance of C. koseri as both a community-acquired and nosocomial neonatal pathogen. Radiologic evidence suggestive of diffuse necrotizing meningo-encephalitis in combination with pneumocephalus and pneumatosis oculi in Citrobacter infections has never been described before. Diagnostic imaging with computed tomographic scanning of the brain and initiation of broad-spectrum antibiotics with good penetration into cerebrospinal fluid are indicated as soon as infection with Citrobacter species is suspected clinically, with appearance of pneumatosis oculi as a rare, late finding.     

Time-dependent inhibition and tetrahydrobiopterin depletion of endothelial nitric-oxide synthase caused by cigarettes.

Smoking causes a dysfunction in endothelial nitric-oxide synthase (eNOS), which is ameliorated, in part, by administration of tetrahydrobiopterin (BH(4)). The exact mechanism by which the nitric oxide deficit occurs is unknown. We have previously shown that aqueous extracts of chemicals in cigarettes (CE) cause the suicide inactivation of neuronal NO synthase (nNOS) by interacting at the substrate-binding site. In the current study, we have found that CE directly inactivates eNOS by a process that is not affected by the natural substrate l-arginine and is distinct from the mechanism of inactivation of nNOS. We discovered that CE causes a time-, concentration-, and NADPH-dependent inactivation of eNOS in an in vitro system containing the purified enzyme, indicating a metabolic component to the inactivation. The CE-treated eNOS but not nNOS was nearly fully reactivated upon incubation with excess BH(4), suggesting that BH(4) depletion is a potential mechanism of inactivation. Moreover, in the presence of CE, eNOS catalyzed the oxidation of BH(4) to dihydrobiopterin and biopterin by a process attenuated by high concentrations of superoxide dismutase but not catalase. We speculate that a redox active component in CE, perhaps a quinone compound, causes oxidative uncoupling of eNOS to form superoxide, which in turn oxidizes BH(4). The discovery of a direct inactivation of eNOS by a compound(s) present in tobacco provides a basis not only for further study of the mechanisms responsible for the biological effects of tobacco but also a search for a potentially novel inactivator of eNOS.     

Helical CT in the primary trauma evaluation of the cervical spine: an evidence-based approach

This review provides a summary of the cost-effectiveness, clinical utility, performance, and interpretation of screening helical cervical spine CT for trauma patients. Recent evidence supports the use of helical CT as a cost-effective method for screening the cervical spine in high-risk trauma patients. Screening cervical spine CT can be performed at the time of head CT to lower the cost of the evaluation, and when all short- and long-term costs are considered, CT may actually save money when compared with traditional radiographic screening. In addition to having higher sensitivity and specificity for cervical spine injury, CT screening also allows more rapid radiological clearance of the cervical spine than radiography. Patients who are involved in high-energy trauma, who sustain head injury, or who have neurological deficits are candidates for CT screening. Screening with CT may enhance detection of other potentially important injuries of the cervical region. Received: 17 March Revision requested: 14 April 2000 Revision received: 19 July 2000 Accepted: 19 July 2000     

Biomarker changes during neoadjuvant anastrozole, tamoxifen, or the combination: influence of hormonal status and HER-2 in breast cancer--a study from the IMPACT trialists.

PURPOSE: To investigate the relationships between biomarker changes in breast cancer during neoadjuvant (preoperative) endocrine therapy. PATIENTS AND METHODS: The IMPACT trial compared the preoperative use of tamoxifen with anastrozole alone or in combination in postmenopausal women (n = 330) with primary breast cancer. Biomarkers were measured in tumor biopsy specimens taken at baseline, and after 2 and 12 weeks of treatment. RESULTS: 52 (93%) of 56, 46 (85%) of 54, and 37 (84%) of 44 patients in the anastrozole, tamoxifen, and combination groups, respectively. There was a significantly greater suppression of Ki67 in the anastrozole-treated group than in the tamoxifen- or combination-treated groups, which is parallel to the greater efficacy seen for anastrozole over these two treatments in the Arimidex, Tamoxifen, Alone or in Combination adjuvant trial. A positive relationship was noted between estrogen-receptor level and Ki67 suppression in all patients. Ki67 was reduced to a greater extent in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors. HER-2-negative tumors tended to show a greater reduction in Ki67 compared with HER-2-positive tumors, but the difference was only significant in the tamoxifen group after 2 weeks, and in the anastrozole group after 12 weeks. CONCLUSION: These results confirm the value of Ki67 as a molecular marker, and provide information regarding the relationships between treatment-induced changes in Ki67 and other important biomarkers. Studies such as this should help integrate agents targeted at growth factor signaling with endocrine agents in breast cancer.     

Clinicopathologic and genetic profile of intracranial marginal zone lymphoma: a primary low-grade CNS lymphoma that mimics meningioma.

PURPOSE: Although rare overall, marginal zone B-cell lymphoma (MZBCL) is the most common primary low-grade CNS lymphoma reported in the literature. The aim of this study is to elucidate the biology and genetic features of this unusual tumor. PATIENTS AND METHODS: Fifteen CNS MZBCLs were studied clinically, pathologically, and genetically, including fluorescent in situ hybridization analyses with commercially available MALT1 and IgH break-apart and centromere 3, 7, 12, and 18 probes. RESULTS: CNS MZBCLs preferentially affect middle-aged women (female-to-male ratio, 4:1), with 93% presenting as dural-based masses mimicking meningioma. Ten patients with 1 to 7.6 years of follow-up after diagnosis showed no evidence of disease after radiation and/or chemotherapy. Like MZBCLs outside of the CNS, they consisted of CD20+, CD3- small B lymphocytes with varying degrees of plasmacytic differentiation and predominantly kappa light-chain restriction (78%). Lymphoid follicles with follicular colonization were seen in three patients and deposition of amyloid was noted in samples from two patients, one of which was tumefactive. Neither Bcl-6 protein nor Epstein-Barr virus-encoded RNA was expressed. Trisomy 3 was detected in six of 12 patients, with no rearrangements of MALT1 or IgH and no trisomies of 7, 12, or 18 detected. CONCLUSION: Our data suggest that intracranial MZBCL is an indolent primary CNS lymphoma that typically presents as a meningioma-like dural-based mass. Trisomy 3, but not MALT1 or IgH translocation, is a common genetic abnormality that may contribute to the pathogenesis of this CNS lymphoma.     

An optimisation algorithm for determination of treatment margins around moving and deformable targets.

PURPOSE: Determining treatment margins for inter-fractional motion of moving and deformable clinical target volumes (CTVs) remains a major challenge. This paper describes and applies an optimisation algorithm designed to derive such margins. MATERIAL AND METHODS: The algorithm works by expanding the CTV, as determined from a pre-treatment or planning scan, to enclose the CTV positions observed during treatment. CTV positions during treatment may be obtained using, for example, repeat CT scanning and/or repeat electronic portal imaging (EPI). The algorithm can be applied to both individual patients and to a set of patients. The margins derived will minimise the excess volume outside the envelope that encloses all observed CTV positions (the CTV envelope). Initially, margins are set such that the envelope is more than adequately covered when the planning CTV is expanded. The algorithm uses an iterative method where the margins are sampled randomly and are then either increased or decreased randomly. The algorithm is tested on a set of 19 bladder cancer patients that underwent weekly repeat CT scanning and EPI throughout their treatment course. RESULTS: From repeated runs on individual patients, the algorithm produces margins within a range of +/-2 mm that lie among the best results found with an exhaustive search approach, and that agree within 3mm with margins determined by a manual approach on the same data. The algorithm could be used to determine margins to cover any specified geometrical uncertainty, and allows for the determination of reduced margins by relaxing the coverage criteria, for example disregarding extreme CTV positions, or an arbitrarily selected volume fraction of the CTV envelope, and/or patients with extreme geometrical uncertainties. CONCLUSION: An optimisation approach to margin determination is found to give reproducible results within the accuracy required. The major advantage with this algorithm is that it is completely empirical, and it is therefore particularly useful for CTVs where the geometrical uncertainties are difficult to model, such as the bladder.