Medullary nephrocalcinosis and pancreatic calcifications demonstrated by ultrasound and CT in infants after treatment with ACTH

Thirteen patients who had undergone prolonged adrenocorticotropic hormone (ACTH) therapy for infantile spasms or myoclonic encephalopathy were examined with sonography. Nine patients were found to have appearances characteristic of medullary nephrocalcinosis. In each of these infants the cortical echogenicity was normal in the presence of focal areas of increased echogenicity within the renal pyramids. Five patients also showed a homogeneously increased echogenicity of the whole pancreas on sonography, and two of these showed increased density on computed tomography. Density measurements were in the range of calcific material within the papillae and pancreatic tissue. On abdominal survey radiographs, even in retrospect no calcifications could be recognized.     

Dynamic and static phantoms for evaluation of digital subtraction angiographic systems

Two types of phantoms were developed with which to evaluate the overall performance of digital subtraction angiography (DSA) systems. A dynamic phantom, called a "fish bone" phantom, consists of polyethylene tubes that simulate blood vessels with various lesions, such as stenoses, ulcers, and aneurysms. With this phantom, washout curves were obtained representing the relationship between iodine content and time. It will be useful for qualitative assessment of DSA images, evaluation of different image-processing schemes, and studies of blood flow analysis. A static phantom, called a "C-D" phantom, can be used for measurement of quantitative contrast-detail (C-D) diagrams and for daily monitoring of DSA systems. This was constructed of tubes of seven different diameters (2.15-0.28 mm) and 14 different concentrations of contrast medium (100%-1.1% Renografin-76 [meglumine and sodium diatrizoate]). The C-D diagrams were determined from an observer performance study using C-D phantom images obtained at four different DSA settings.     

Brain tumors: MR imaging with gadolinium-DTPA

Magnetic resonance (MR) imaging was performed on 40 patients with intracranial tumors, before and after intravenous administration of gadolinium-DTPA (Gd-DTPA). Precontrast studies included a comprehensive protocol of spin-echo sequences. Tumors were visualized on precontrast images either directly or indirectly by anatomic distortion caused by the mass. However, differentiation of the tumor from adjacent tissues was possible in only 17 of 40 cases. Delineation of the tumor was best on precontrast, T2-weighted images. After administration of Gd-DTPA (0.1 mmol/kg), increased signal intensity from the tumor was observed in all patients. The localized increase in signal intensity in the tumor considerably improved the tumor delineation in 36 of 40 patients. Whereas most of the meningiomas, neuromas, and adenomas could be delineated prior to administration of contrast material if appropriate pulse sequences were applied, glioblastomas and intracranial metastases required Gd-DTPA administration for diagnostically sufficient tumor display.     

Acute lymphoblastic leukemia of childhood: identification of two distinct regions of deletion on the short arm of chromosome 12 in the region of TEL and KIP1

Cytogenetic analysis of acute lymphoblastic leukemia (ALL) of childhood identified nonrandom chromosomal abnormalities of the short arm of chromosome 12. The alterations include deletions that are thought to be indicative of the presence of a tumor suppressor gene that is mutated on the remaining allele. To refine further the chromosomal localization of this gene, we analyzed the loss of heterozygosity (LOH) of chromosome 12 in 100 primary ALL samples using 22 polymorphic markers and identified two distinct smallest common deleted regions on chromosome 12p13. One region is flanked by D12S77 and D12S98 and has a size of 4 cM. Twenty-six percent of informative patients showed LOH in this region. This region may contain the TEL gene. The other region is flanked by D12S269 and D12S308 including the KIP1 gene. Forty-four percent of informative patients showed LOH in this second region. Mutational analysis of KIP1 using polymerase chain reaction-single- strand conformation polymorphism analysis and Southern blot analysis showed no homozygous deletions and point mutations suggesting that the altered gene in this second region is not the KIP1. Clinical data showed that LOH of 12p was demonstrated more frequently in precursor-B ALLs (32 of 80; 40%) than in T-ALLs (1 of 20; 5%) (P = .0027). Furthermore, patients with 12p LOH were younger (P = .013), with a lower DNA index (P = .046), but they had the same survival rates at 3 years. In summary, these data suggest that two different tumor suppressor genes are on chromosome arm 12p, which act separately in the development of childhood precursor-B ALLs. One of the tumor suppressor genes is in the region the KIP1 gene, but our data suggest this gene is not abnormal. The other target is in the region of the TEL gene; and this candidate deserves further study.     

Improving behaviour in self-testing (IBIS): Study on frequency of use,consequences, information needs and use,and quality of currently available consumer information (protocol)

Background  

Self-tests are available to consumers for more than 25 conditions, ranging from infectious diseases to cardiovascular risk factors. Self-tests are defined as in-vitro tests on body materials such as blood, urine, faeces, or saliva that are initiated by consumers to diagnose a particular disorder or risk factor without involving a medical professional. In 2006, 16% of a sample of Dutch Internet users had ever used at least one self-test and 17% intended to use a self-test in the future. The objectives of this study are to determine (1) the frequency of self-test use, (2) the consumers' reasons for using or not using a self-test, (3) the information that is used by self-testers in the different self-test stages and the consumers' interpretation of the quality of this information, (4) the consumers' response to self-test results in terms of their confidence in the result, reassurance by the test result, and follow-up behaviour, (5) the information consumers report to need in the decision making process of using or not using a self-test, and in further management on the basis of the self-test result, and (6) the quality of the currently available consumer information on a selected set of self-tests.     

Reliable and valid NEWS for Chinese seniors: measuring perceived neighborhood attributes related to walking

Background

The effects of the built environment on walking in seniors have not been studied in an Asian context. To examine these effects, valid and reliable measures are needed. The aim of this study was to develop and validate a questionnaire of perceived neighborhood characteristics related to walking appropriate for Chinese seniors (Neighborhood Environment Walkability Scale for Chinese Seniors, NEWS-CS). It was based on the Neighborhood Environment Walkability Scale - Abbreviated (NEWS-A), a validated measure of perceived built environment developed in the USA for adults. A secondary study aim was to establish the generalizability of the NEWS-A to an Asian high-density urban context and a different age group.

Methods

A multidisciplinary panel of experts adapted the original NEWS-A to reflect the built environment of Hong Kong and needs of seniors. The translated instrument was pre-tested on a sample of 50 Chinese-speaking senior residents (65+ years). The final version of the NEWS-CS was interviewer-administered to 484 seniors residing in four selected Hong Kong districts varying in walkability and socio-economic status. Ninety-two participants completed the questionnaire on two separate occasions, 2-3 weeks apart. Test-rest reliability indices were estimated for each item and subscale of the NEWS-CS. Confirmatory factor analysis was used to develop the measurement model of the NEWS-CS and cross-validate that of the NEWS-A.

Results

The final version of the NEWS-CS consisted of 14 subscales and four single items (76 items). Test-retest reliability was moderate to good (ICC > 50 or % agreement > 60) except for four items measuring distance to destinations. The originally-proposed measurement models of the NEWS-A and NEWS-CS required 2-3 theoretically-justifiable modifications to fit the data well.

Conclusions

The NEWS-CS possesses sufficient levels of reliability and factorial validity to be used for measuring perceived neighborhood environment in Chinese seniors. Further work is needed to assess its construct validity and generalizability to other Asian locations. In general, the measurement model of the original NEWS-A was generalizable to this study context, supporting the feasibility of cross-country and age-group comparisons of the effect of the neighborhood environment on walking using the NEWS-A as a tool to measure the perceived built environment.     

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy

Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.     

Endoplasmic reticulum chaperone gp96 in macrophages is essential for protective immunity during Gram‐negative pneumonia

Klebsiella pneumoniae is among the most common Gram‐negative bacteria that cause pneumonia. Gp96 is an endoplasmic reticulum chaperone that is essential for the trafficking and function of Toll‐like receptors (TLRs) and integrins. To determine the role of gp96 in myeloid cells in host defence during Klebsiella pneumonia, mice homozygous for the conditional Hsp90b1 allele encoding gp96 were crossed with mice expressing Cre‐recombinase under control of the LysM promoter to generate LysMcre‐Hsp90b1‐flox mice. LysMcre‐Hsp90b1‐flox mice showed absence of gp96 protein in macrophages and partial depletion in monocytes and granulocytes. This was accompanied by almost complete absence of TLR2 and TLR4 on macrophages. Likewise, integrin subunits CD11b and CD18 were not detectable on macrophages, while being only slightly reduced on monocytes and granulocytes. Gp96‐deficient macrophages did not release pro‐inflammatory cytokines in response to Klebsiella and displayed reduced phagocytic capacity independent of CD18. LysMcre‐Hsp90b1‐flox mice were highly vulnerable to lower airway infection induced by K. pneumoniae, as reflected by enhanced bacterial growth and a higher mortality rate. The early inflammatory response in Hsp90b1‐flox mice was characterized by strongly impaired recruitment of granulocytes into the lungs, accompanied by attenuated production of pro‐inflammatory cytokines, while the inflammatory response during late‐stage pneumonia was not dependent on the presence of gp96. Blocking CD18 did not reproduce the impaired host defence of LysMcre‐Hsp90b1‐flox mice during Klebsiella pneumonia. These data indicate that macrophage gp96 is essential for protective immunity during Gram‐negative pneumonia by regulating TLR expression. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.