Accuracy and completeness of the registration of childhood leukaemia in The Netherlands, 1989-1992

In the Netherlands, childhood leukaemia is recorded by the Dutch Childhood Leukaemia Study Group (DCLSG, set up in 1972) and by nine regional cancer registries which together form the Netherlands Cancer Registry (NCR, set up in 1989). The data files from the incidence years 1989-1992 of the two registries were linked in order to evaluate accuracy and completeness and to calculate and equalise the incidence rates for childhood leukaemia in The Netherlands. Unlinked records or records with disagreements (birth date, sex, type of leukaemia and incidence date) were checked by the DCLSG and by the regional cancer registries. The DCLSG recorded 431 cases of childhood leukaemia, while the NCR recorded 434 cases. After record linkage and review of the cases, it was concluded the 445 records should have been recorded as childhood leukaemia. The NCR had recorded 425 of the 445 correct cases (95.5%), but had missed 20 cases (4.5%). The DCLSG had recorded 431 of the 445 correct cases (96.9%) and had missed 14 cases (3.1%). In addition, the NCR had recorded 9 cases incorrectly as childhood leukaemia. Part of the disagreement was caused by differences in coding rules (definition of non-Hodgkin's lymphoma (NHL) and the myelodysplastic syndrome versus leukaemia). It could be concluded that the quality and completeness of the two registries was very high. Regular comparison of the recorded data will help to reveal the inherently problematic disagreement between definitions and coding.     

Anatomical and surgical aspects of splenic segmentectomies

Cypermethrin is a synthetic pyrethroid that belongs to a group of insecticides with low mammalian toxicity but high insecticidal activity. The present study was designed to investigate the toxicity of cypermethrin on freshly isolated hepatocytes from male and female rats. Hepatocytes were harvested by a collagenase perfusion technique and were exposed to different concentrations of cypermethrin (100, 200, 400, or 800 ng/2 x 10(6) cells) for up to 2 h. Cell viability and the leakage of aspartate transaminase (AST) and alanine transaminase (ALT) were determined throughout the incubation period. The cell viability of the hepatocytes from male and female rats exposed to 400 ng and 800 ng was significantly reduced after 60 and 30 min of incubation, respectively. With cells from female rats, viability was also reduced upon exposure to 200 ng cypermethrin for 2 h. The decrease in cell viability was dose and time dependent. The leakage of ALT and AST was significantly increased with 400 and 800 ng concentrations at 60 and 30 min, respectively. ALT leakage from female hepatocytes was significantly increased at 60 min of incubation with the 200-ng dose, whereas 2 h of incubation was required for the leakage of ALT from the cells of male rats. The present data indicate that cypermethrin has toxic effects on male and female rat hepatocytes in a dose- and time-dependent manner. The data suggest that female rat hepatocytes may be more sensitive to the toxic effects of cypermethrin than male cells.     

Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice

This study demonstrates that endogenously produced interferon gamma (IFN-gamma) forms the basis of a tumor surveillance system that controls development of both chemically induced and spontaneously arising tumors in mice. Compared with wild-type mice, mice lacking sensitivity to either IFN-gamma (i.e., IFN-gamma receptor-deficient mice) or all IFN family members (i.e., Stat1-deficient mice) developed tumors more rapidly and with greater frequency when challenged with different doses of the chemical carcinogen methylcholanthrene. In addition, IFN-gamma-insensitive mice developed tumors more rapidly than wild-type mice when bred onto a background deficient in the p53 tumor-suppressor gene. IFN-gamma-insensitive p53(-/-) mice also developed a broader spectrum of tumors compared with mice lacking p53 alone. Using tumor cells derived from methylcholanthrene-treated IFN-gamma-insensitive mice, we found IFN-gamma's actions to be mediated at least partly through its direct effects on the tumor cell leading to enhanced tumor cell immunogenicity. The importance and generality of this system is evidenced by the finding that certain types of human tumors become selectively unresponsive to IFN-gamma. Thus, IFN-gamma forms the basis of an extrinsic tumor-suppressor mechanism in immunocompetent hosts.     

Arrhythmia detection and response in a monitoring technician and pocket paging system

Technologically advanced telemetry systems have begun to produce alternatives to the need for continuous visual observation of the electrocardiogram (ECG). Few studies have been conducted to determine the efficacy of these systems in the clinical setting. The purpose of this study was to describe two different approaches to communication of arrhythmia events and corresponding nurse response. One approach, on a cardiac medical unit, utilized a monitoring technician to continuously observe ECGs at a central monitoring technician station (MTS) and notify the nurse of changes. The other approach, on a general medical unit, eliminated the use of the monitoring technician and utilized a pocket paging system (PPS). The PPS interfaced with the computerized arrhythmia detection system from the ECG monitor, which directly alerted the nurse to arrhythmia events. A quasi-experimental comparative post-test design was used. The sample consisted of 50 randomly selected, 2-hour observation periods on each unit during a 3-month period. Data collectors recorded the interaction of the monitoring technician with the arrhythmia detection system and the nurse on the MTS unit, or the nurse using the PPS. Results of this study revealed all arrhythmia events activated an alarm by the computerized arrhythmia detection system. Length of time to notify the nurse was within 0 to 1 minute for both systems. This study demonstrated that the PPS is a viable approach to arrhythmia detection and communication in the medical/cardiac patient population.     

MR identification of white matter abnormalities in multiple sclerosis: a comparison between 1.5 T and 4 T

BACKGROUND AND PURPOSE: Although MR spectroscopy and functional MR imaging of the brain have been successful at 4 T, conventional fast spin-echo imaging of the brain at 4 T has not been adequately evaluated. The purpose of this study was to compare the detection of white matter abnormalities in multiple sclerosis (MS) at 1.5 T and 4 T. METHODS: Fifteen patients with clinically definite MS were imaged at both 1.5 T and 4 T within a 1-week period. Comparison was made between fast spin-echo long-TR images at both field strengths. Pulse sequences were tailored to maximize resolution and signal-to-noise ratio in clinically relevant imaging times (< 7 min). Four interpreters independently reviewed the images obtained at both field strengths in separate sessions and evaluated them for lesion identification, size, characterization, and subjective resolution. Differences in interpretations at 1.5 T and 4 T were subsequently recorded. RESULTS: Images obtained at 4 T showed a mean of 88 more lesions as compared with images obtained at 1.5 T. All the lesions measured less than 5 mm and were typically aligned along perivascular spaces. Twenty-five consensually identified lesions on 4-T images were not seen at all on 1.5-T images. Moreover, 4-T images showed 56 additional consensually identified lesions, which were indistinct and seen only in retrospect on 1.5-T images. These lesions were frequently (n = 48) identified in large confluent areas of white matter signal intensity abnormality at 1.5 T. All observers also agreed that 4-T images subjectively enhanced the perception of normal perivascular spaces and small perivascular lesions. CONCLUSION: MR imaging at 4 T can depict white matter abnormalities in MS patients not detectable at 1.5 T through higher resolution with comparable signal-to-noise ratio and imaging times.     

Inducible nitric-oxide synthase generates superoxide from the reductase domain

In the absence of L-arginine, the heme center of the oxygenase domain of neuronal nitric-oxide synthase reduces molecular oxygen to superoxide (O-2). Our recent work has provided evidence that inducible NOS (iNOS) may also catalyze O-2 formation in macrophages. However, there has been a lack of direct evidence of superoxide generation from the purified iNOS, and it was previously hypothesized that significant O-2 production does not occur. Moreover, the mechanism and enzyme site responsible for O-2 generation is unknown. To determine whether iNOS produces O-2 and to identify the mechanism of this process, we performed electron paramagnetic resonance measurements on purified iNOS using the spin trap 5,5-dimethyl-1-pyrroline N-oxide. In the presence of NADPH, prominent O-2 adduct signals were detected from iNOS. These signals were totally abolished by superoxide dismutase but not affected by catalase. High concentrations of L-arginine decreased this O-2 formation, whereas its enantiomer D-arginine did not. Pre-incubation of iNOS with the flavoprotein inhibitor diphenyleneiodonium totally blocked these O-2 signals. Conversely, pretreatment of the enzyme with the heme blocker cyanide had no effect on O-2 generation. Furthermore, strong O-2 generation was directly detected from the isolated iNOS reductase domain. Together, these data demonstrate that iNOS does generate O-2, and this mainly occurs at the flavin-binding sites of the reductase domain.