Predictors of outcome in small cell carcinoma of the cervix--a case series

OBJECTIVE: The objective of this study was to determine whether clinicopathologic findings or the immunohistochemical presence of molecular markers are predictive of clinical outcome in patients with small cell carcinoma of the cervix (SCCC). METHODS: A retrospective review of cases of carcinoma of the cervix was conducted to identify SCCC. From 1978 to 1999, 16 patients were identified at our institution with the diagnosis of SCCC. Microscopic sections of paraffin-embedded tissue specimens were evaluated for confirmation of diagnosis. Specimens were immunohistochemically stained with antibodies to three neuroendocrine markers: neuron-specific enolase, chromagranin (CGR), and synaptophysin. Specimens were also stained for protein expression of p53, erbB2, proliferating cell nuclear antigen, and c-myc. The relationship between molecular markers and clinical outcome was determined. RESULTS: All 16 cases met the histologic criteria for SCCC. Fourteen of 16 tumors (88%) stained positive for neuroendocrine differentiation. Eleven of 16 patients (69%) died from disease with a median survival of 19 months; there were 3 long-term survivors (greater than 5 years). CGR was positive in 8 (50%) specimens and was found to be highly predictive of death (P = 0.001). Complete loss of p53 protein was seen in 8 patients, 7 of whom died with a median survival of 20 months. CONCLUSION: Immunohistochemistry can be helpful in confirming difficult cases of SCCC. Further studies are necessary to define molecular markers that may be predictive of outcome in patients with SCCC.     

Variations in pleural fluid WBC count and differential counts with different sample containers and different methods

OBJECTIVE: To compare the results of pleural fluid analysis for WBC counts and differential cell counts as follows: (1) counting performed manually vs that performed by an automated cell counter; (2) cells collected in different types of specimen containers; and (3) cell counts performed at 4 and 24 h postthoracentesis. METHODS: Twenty-eight pleural fluid samples were each collected in five different containers (ie, ethylenediaminetetraacetic acid (EDTA)-treated glass, citrate-treated glass, heparinized glass, plain glass, and plain plastic tubes). The WBC counts and differential cell counts were obtained manually (on the EDTA tube) and with an automated counter on all tubes within 4 h of collection, and again after 24 h of refrigeration. RESULTS: There was a close correlation between the WBC counts obtained manually and those obtained with the automated counter from the pleural fluid samples collected in the EDTA tubes (r = 0.92). With the automated counter, the pleural fluid WBC counts were similar among the three tubes containing anticoagulants, but the counts obtained from the tubes without anticoagulants were significantly lower. The differential cell counts obtained manually and those obtained with the automated cell counter differed substantially. Although the percentage of lymphocytes was similar, the automated counter was inaccurate in differentiating neutrophils from large monocytes or mesothelial cells. The WBC counts obtained within 4 h of collection and 24 h after collection were virtually identical. CONCLUSIONS: The WBC counts obtained manually and with the automated counter from pleural fluid samples in EDTA tubes correlated very closely. The pleural fluid WBC count was lower if the pleural fluids had been collected in tubes without an anticoagulant. Automated WBC counts from pleural fluid specimens were inaccurate, possibly due to difficulty in separating neutrophils from monocyte/mesothelial cells. Refrigerated storage for up to 24 h had no significant effect on the total WBC count or on the WBC count differential regardless of the tube utilized.     

Environmental influences: factors influencing a woman's decision to use dietary supplements

Use of dietary supplements by women, particularly those over 40 years of age may be widespread in the United Kingdom. However, from surveillance data, there appears to be a disparity between nutrition and health needs and the rationale for and actual use of dietary supplements by women. This apparent paradox forms the basis for an inverse supplement hypothesis (i.e., supplement use in women appears to be most prevalent among those with least need). Little research has been done to examine the factors underlying the decision to use dietary supplements. Reasons for consuming dietary supplements are often complex, combining social, psychological, knowledge and economic factors. The theory of planned behavior is a widely used model for assessing factors influencing behavioral motivation and action that may be useful for assessing specific diet- and nutrition-related practices. It provided the basis for the development of a questionnaire to explore overall dietary supplement use in a cohort of women in the United Kingdom. The analysis of factors related to beliefs underlying dietary supplement use revealed differences between supplement users and nonusers. Differences included a stronger belief by users than nonusers that taking dietary supplements ensures against possible ill health. Both users and nonusers of supplements also perceived the media (books and magazines) to be a powerful influence on a person's decision to use supplements. These findings highlight the potential of the theory of planned behavior in exploring supplement-taking behavior while throwing light on the factors influencing an individual's motivations to use dietary supplements.     

Body weight, body-weight concerns and eating styles in habitual heavy users and non-users of artificially sweetened beverages

This study investigated reported body weight, concerns about body weight and eating styles in habitual heavy users (consume>825 ml/day) and habitual non-users of artificially sweetened beverages (ASBs). Groups of habitual heavy users (N=51) and non-users (N=69) were compared on measures of weight using self-reported body mass index (BMI), and measures of weight concern and eating style using the Dutch Eating Behaviors Questionnaire (DEBQ), the Yale Eating Patterns Questionnaire (YEPQ), and the Eating Disorder Inventory (EDI). Habitual heavy users reported higher body weights (BMI), greater concerns about weight and greater tendencies toward certain eating styles, when compared to non-users. Using logistic regression, 82% of respondents were correctly classified as heavy or non-users of ASBs using body mass index and body-weight concerns. Associations between a heavy use of ASBs and certain eating styles can be explained by association with high body weights and concerns about body weight.     

Prolonged QT interval and cardiac arrhythmias in two neonates: sudden infant death syndrome in one case

Two neonates with arrhythmias and the long QT syndrome are described. The arrhythmias were detected in utero and both infants were apparently well after birth. The first infant, although well, had a bradycardia for the first 9 days of life. A normal heart rate was documented at 10 days but a prolonged QT interval was not appreciated on the ECG. He was discharged from hospital but died suddenly and unexpectedly 3 days later. A post-mortem examination failed to find a cause for his death which therefore fell into the category of the sudden infant death syndrome (SIDS). A retrospective analysis of the perinatal electrocardiogram showed a probable junctional rhythm with 2:1 conduction to the ventricle; the QT interval was prolonged at 0.52 seconds (QTC = 0.63). The second infant had a QT interval of 0.52 seconds (QTC = 0.54) and frequent ventricular premature beats on a 24-hour electrocardiogram. She was treated with propranolol and remains well 2 years later. Sudden infant death has often been described in the siblings of children with the long QT syndrome and one other report described a case of SIDS which was said to have had a prolonged QT interval on the perinatal ECG. This report, however, provides unquestionable evidence, in one case, of an association between the long QT syndrome and SIDS.     

Dependence of insulin secretion from permeabilized pancreatic beta-cells on the activation of Ca(2+)/calmodulin-dependent protein kinase II. A re-evaluation of inhibitor studies

Previous studies utilizing inhibitors of the Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II) to address the role of this enzyme in insulin secretion have produced contradictory results. In the current study, these inconsistencies have been addressed by evaluating the effect of various CaM kinase II inhibitors to decrease Ca(2+)-induced insulin secretion from permeabilized beta-cells. KN-93 (2-[N-(2-hydroxyethyl)-N-(4-methoxy-benzenesulfonyl)]-amino-N-(4-chlo rocinnamyl)-N-methylbenzylamine) markedly inhibited both CaM kinase II activation and insulin secretion in parallel in alpha-toxin-permeabilized beta-cells. These effects were specific since they were not mimicked by the inactive analog, KN-92 (2-[N-(4-methoxy-benzenesulfonyl)]-amino-N-(4-chlorocinnamyl)-N-methy lbenzylamine). In contrast, KN-62 (1-[N, O-bis(5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-phenylpiperazine) , while reported to be similar to KN-93 with respect to mechanism of action, did not inhibit Ca(2+)-induced activation of CaM kinase II or insulin secretion in these cell preparations. All three agents suppressed Ca(2+) influx in intact beta-cells induced by depolarization in the presence of elevated extracellular potassium although to different extents. The synthetic peptide inhibitors of CaM kinase II, [Ala(286)]CaMK 281-302 and AIP (autocamtide-2-related inhibitory peptide), strongly inhibited Ca(2+)-induced insulin secretion from electropermeabilized islets, an effect that also correlated with an equivalent inhibition of CaM kinase II activation. This re-evaluation (i) explains a lack of effect of KN-62 on insulin secretion from permeabilized cells based on its inability to inhibit CaM kinase II activation in these preparations; (ii) has revealed that CaM inhibitors, either chemical or peptide in nature, that are capable of preventing enzyme activation uniformly suppress Ca(2+)-sensitive insulin secretion; and (iii) cautions the use of KN-62/93/92 as selective inhibitors of CaM kinase II in intact cell studies. These observations reinforce the suggestion that CaM kinase II plays an important role in insulin exocytosis in the beta-cell.     

Excretory urography with iohexol: evaluation in children

A multicenter clinical study was conducted using iohexol, a second-generation nonionic contrast medium, for excretory urography performed in 130 children. Doses of iohexol (300 mg iodine/ml) ranged between 150 and 660 mgI/kg (0.5 and 2.2 ml/kg). Iohexol was tolerated well, and no significant adverse reactions occurred. Sixty-five iohexol urograms were evaluated to determine the minimum dose for adequate visualization of the kidneys and collecting systems. A dose greater than 300 mgI/kg (1.0 ml/kg) always resulted in a urogram of diagnostic quality, while visualization was insufficient for diagnosis in 10% of studies done with doses of 150-300 mgI/kg (0.5-1.0 ml/kg). Another 65 iohexol urograms were compared in a blinded manner with a similar number of studies performed using iothalamate meglumine at comparable iodine concentration and dose. Visualization of calyces and pelvoinfundibular structures achieved with iohexol was rated better with statistical significance, but there was no difference in visualization of the renal parenchyma or ureters. Use of iohexol in excretory urography may be advantageous in children who are at greatest risk for an adverse reaction to contrast media or in those most likely to benefit from use of a low osmolality contrast agent.     

Volumetric rendering techniques: applications for three-dimensional imaging of the hip

Volumetric rendering is a new approach to three-dimensional (3D) imaging that overcomes many of the drawbacks of currently available surface-rendering systems. Its application on the Pixar Imaging System in two cases of acetabular fracture was assessed to illustrate the features of the technique. The fast-computing architecture and large memory of this system allow rapid generation of a series of high-quality 3D images in each plane of rotation (x or spinal axis, z or somersaulting axis) that can be viewed as independent static images or as an animated real-time video loop. Editing to remove the normal contralateral hemipelvis enhances appreciation of acetabular abnormalities. Every pixel of computed tomographic data is preserved, allowing representation of both soft tissue and bone as translucent overlap. The presentation of data also allows detection of subtle abnormalities and features and minimizes the artifact generation common in surface-rendered images.     

Classifying health‐related behaviours: Exploring similarities and differences amongst behaviours

Objectives. The classification of health behaviours may provide a useful framework for understanding their characteristics and therefore the ways in which they are similar and different. However, to date, little research has attempted to identify these characteristics and explore the dimensions along which behaviours differ. This paper uses an inductive approach to explore this issue. Design and methods. In Study 1, 25 repertory grid interviews and 3 focus groups encompassing lay public and health professionals identified 25 ways of describing health behaviours. These were refined into 11 key characteristics. In Study 2, 180 members of the general public rated 20 health behaviours on each of these characteristics. Results. Principal components analysis indicated behaviours were perceived along three key dimensions: ‘easy immediate pay‐offs’ versus ‘effortful long‐term pay‐offs’; ‘private unproblematic’ versus ‘public and problematic’; and ‘important routines’ versus ‘unimportant one‐offs’. Risk behaviours were clearly differentiated being perceived as ‘easy immediate pay‐offs’ and ‘public–problematic’. In contrast with other approach behaviours such as diet or self‐examination, physical activity behaviours were perceived as ‘effortful long‐term pay‐offs’. Conclusions. This research provides an useful starting point in the development of a framework that allows us to better understand differences and similarities between health behaviours. These dimensions may be important to consider when researchers set out to predict or change behaviour.     

Oncolytic virotherapy reaches adolescence

Lytic viruses kill cells as a consequence of their normal replication life cycle. The idea of harnessing viruses to kill cancer cells arose over a century ago, before viruses were even discovered, from medical case reports of infections associated with cancer remissions. Since then, there has been no shortage of hype, hope, or fear regarding the prospect of oncolytic virotherapy for cancer. Early developments in the field included encouraging antitumor efficacy both in animal studies in the 1920s–1940s and in human clinical trials in the 1950s–1970s. Despite its long‐standing history, oncolytic virotherapy was an idea ahead of its time. Without needed advances in molecular biology, virology, immunology, and clinical research ethics, early clinical trials resulted in infectious complications and were fraught with controversial research conduct, so that enthusiasm in the medical community waned. Oncolytic virotherapy is now experiencing a major growth spurt, having sustained numerous laboratory advances and undergone multiple encouraging adult clinical trials, and is now witnessing the emergence of pediatric trials. Here we review the history and salient biology of the field, including preclinical and clinical data, with a special emphasis on those agents now being tested in pediatric cancer patients. Pediatr Blood Cancer. 2010;55:1253–1263. © 2010 Wiley‐Liss, Inc.