Spontaneous tumor rejection by cbl-b-deficient CD8+ T cells

The concept of tumor surveillance implies that specific and nonspecific components of the immune system eliminate tumors in the early phase of malignancy. Understanding the biochemical mechanisms of tumor immunosurveillance is of paramount significance because it might allow one to specifically modulate spontaneous antitumor activity. We report that inactivation of the E3 ligase Casitas B cell lymphoma-b (Cbl-b) confers spontaneous in vivo rejection of tumor cells that express human papilloma virus antigens. Moreover, cbl-b(-/-) mice develop significantly fewer ultraviolet B (UVB)-induced skin malignancies and reject UVB-induced skin tumors. CD8(+) T cells were identified as key players in the spontaneous tumor rejection response. Loss of Cbl-b not only enhances antitumor reactivity of CD8(+) T cells but also occurs in the absence of CD4(+) T cells. Mechanistically, cbl-b(-/-) CD8(+) T cells are resistant to T regulatory cell-mediated suppression and exhibit enhanced activation and rapid tumor infiltration. Importantly, therapeutic transfer of naive cbl-b(-/-) CD8(+) T cells is sufficient to mediate rejection of established tumors. Even up to 1 yr after the first encounter with the tumor cells, cbl-b(-/-) mice carry an "anticancer memory." These data identify Cbl-b as a key signaling molecule that controls spontaneous antitumor activity of cytotoxic T cells in different cancer models. Inhibition of Cbl-b is a novel approach to stimulate long-lasting immunity against cancer.     

Keeping newborns warm: beliefs,practices and potential for behaviour change in rural Ghana

Objectives This study aimed to collect data on thermal care practices in rural Ghana to inform the design of a community newborn intervention. Methods All 635 women who delivered in six districts in Ghana in the first 2 weeks of December 2006 were interviewed about immediate newborn care. Qualitative data on thermal care practices and barriers and facilitators to behaviour change were collected from recently delivered/pregnant women, birth attendants/grandmothers, and husband through birth narratives, in‐depth interviews and focus group discussion. Results Respondents knew that keeping the baby warm was essential for health but 71% of babies born at home had delayed drying, 79% delayed wrapping, 93% early bathing and 10% were placed skin‐to‐skin. Birth attendants were usually in charge of mother and baby immediately after birth. Delays in drying/wrapping were linked to leaving the baby unattended until the placenta was delivered. Early bathing was linked to reducing body odour in later life, shaping the baby’s head, and helping the baby sleep and feel clean. Respondents thought that changing bathing behaviours would be difficult, especially as babies are bathed early in facilities. The concept of skin‐to‐skin care was easily understood and most women said they would try it if it was good for the baby. Conclusion Thermal care is a key component of community newborn interventions, the design of which should be based on an understanding of current behaviours and beliefs. Formative research can help select focus behaviours, decide who to include in interventions, ensure consistent messages and determine what messages and approaches are needed to overcome behaviour change barriers.     

No evidence of association of FLJ10986 and ITPR2 with ALS in a large German cohort

A recent genome-wide association study (GWAS) found significant association of six single nucleotide polymorphisms (SNPs) in the gene FLJ10986 with sporadic amyotrophic lateral sclerosis (SALS). Another independent GWAS reported significant association of one SNP in the gene inositol 1,4,5-triphosphate receptor 2 (ITPR2) with SALS. These studies provided conflicting results. We examined the six most significant SNPs in FLJ10986 and one SNP in ITPR2 in a large cohort consisting of 595 SALS cases and 681 controls ascertained from Germany. Our results did not provide evidence for the association of these SNPs with SALS, suggesting a possible population-specific effect for FLJ10986 and ITPR2 that do not modulate the risk for SALS in the German population.     

CALLA negative precursor B lymphoblastic leukemia with MLL gene translocation and an unusual FISH signal pattern

Rearrangements of the mixed lineage leukemia (MLL) gene at 11q23 commonly occur in infants with CALLA negative B lymphoblastic leukemia (B-ALL). Most often, these are detected by conventional karyotyping; however, fluorescent in-situ hybridization (FISH) with the help of a dual-color break-apart probe is used to identify cryptic translocations. When there is an MLL gene translocation, the usual FISH signal pattern is 1 red-1 green-1 yellow fusion signal pattern. We present a case of an infant with CALLA negative precursor B-ALL with a characteristic translocation t(4;11) (q21;q23), however, with an unusual MLL FISH signal pattern.     

Performance characteristics and comparison of Abbott and artus real-time systems for hepatitis B virus DNA quantification

Virological monitoring of hepatitis B virus (HBV) DNA is critical to the management of HBV infection. With several HBV DNA quantification assays available, it is important to use the most efficient testing system for virological monitoring. In this study, we evaluated the performance characteristics and comparability of three HBV DNA quantification systems: Abbott HBV real-time PCR (Abbott PCR), artus HBV real-time PCR with QIAamp DNA blood kit purification (artus-DB), and artus HBV real-time PCR with the QIAamp DSP virus kit purification (artus-DSP). The lower limits of detection of these systems were established against the WHO international standards for HBV DNA and were found to be 1.43, 82, and 9 IU/ml, respectively. The intra-assay and interassay coefficients of variation of plasma samples (1 to 6 log(10) IU/ml) ranged between 0.05 to 8.34% and 0.16 to 3.48% for the Abbott PCR, 1.53 to 26.85% and 0.50 to 12.89% for artus-DB, and 0.29 to 7.42% and 0.94 to 3.01% for artus-DSP, respectively. Ninety HBV clinical samples were used for comparison of assays, and paired quantitative results showed strong correlation by linear regression analysis (artus-DB with Abbott PCR, r = 0.95; Abbott PCR with artus-DSP, r = 0.97; and artus-DSP with artus-DB, r = 0.94). Bland-Altman analysis showed a good level of agreement for Abbott PCR and artus-DSP, with a mean difference of 0.10 log(10) IU/ml and limits of agreement of -0.91 to 1.11 log(10) IU/ml. No genotype-specific bias was seen in all three systems for HBV genotypes A, C, and D, which are predominant in this region. This finding illustrates that the Abbott real-time HBV and artus-DSP systems show more comparable performance than the artus-DB system, meeting the current guidelines for assays to be used in the management of hepatitis B.     

Combined trans-sphenoidal and simultaneous trans-ventricular-endoscopic decompression of a giant pituitary adenoma: case report

Objective  This is the first report of the simultaneous combined use of trans-sphenoidal and trans-ventricular-endoscopic route for decompression of a giant pituitary adenoma. Method  A 38 year old man presented to us with symptoms of raised intracranial pressure along with visual and hypothalamic disturbances. The CT scan revealed destruction of the sella by a large (5 × 3.5 × 2.5 cm) well defined enhancing mass in the sella and suprasellar region extending laterally up to the cavernous sinuses and both carotid arteries and superiorly into the lumen of the 3rd ventricle producing obstructive hydrocephalus. On T2WI of the non-contrast MRI scan the mass was iso-intense to grey matter suggesting the possibility of a firm nature of the adenoma. The tumour was first approached by the standard trans-sphenoidal route and as predicted from the pre-operative MRI, the tumour was found to be firm and not amenable to suction. After decompression of the intra-sellar part of the tumour, the intracranial pressure was raised in an attempt to make the remainder of the tumour descend into the sella but without success. The suprasellar part of the tumour was then simultaneously addressed via a trans-ventricular-endoscopic route but the firm tumour did not yield to endoscopic instruments viz. biopsy forceps, angiographic catheter and electrosurgical probes. It was then gently pushed down towards the sella and decompressed piecemeal by using trans-sphenoidal instruments. The sellar cavity was reconstructed using fat, fascia lata graft and a piece of septal bone. Results  Post-operatively, the patient showed a remarkable improvement of his symptoms of raised intracranial pressure, hypothalamic dysfunction and visual disturbances. Follow-up imaging at 2 months and 1 year, did not show any residual or recurrent tumour. Conclusions  This novel technique of the combined trans-sphenoidal and simultaneous trans-ventricular-endoscopic approach is a viable option for patients with giant fibrous pituitary adenoma when the tumour is not yielding to the trans-sphenoidal route alone.     

Paradoxical clustering of brain metastases in an underperfused cerebral hemisphere

OBJECTIVE: To describe a patient with a predominantly unilateral intracranial arterial stenosis who then developed metastatic lung cancer to the brain, with the tumors preferentially depositing in the underperfused cerebral hemisphere. DESIGN: Case report. SETTING: Inpatient neurology ward at a university medical center. Patient A 68-year-old woman with intracerebral arterial stenosis who then developed lung cancer with multiple metastases to the brain in an asymmetric arrangement. Main Outcome Measure The location of metastatic tumor deposits in relation to intracerebral arterial stenosis in the cerebral hemispheres of our patient. RESULTS: In this patient, most of the metastatic tumors were located in the underperfused cerebral hemisphere. CONCLUSIONS: This case demonstrates the concept that emboli washout by vigorous circulation is more important than direct delivery of embolic material in determining whether tumor cells will implant and grow in the brain.     

Low-density lipoprotein cholesterol in patients treated with atypical antipsychotics: missed targets and lost opportunities

BACKGROUND: The treatment of psychotic disorders with second-generation antipsychotics (SGAs) has been linked to an increased risk of coronary heart disease (CHD). Lowering low-density lipoprotein-cholesterol (LDL-C) to individualized targets of 100, 130 or 160 mg/dl reduces the risk of CHD. We determined the prevalence of above-target LDL-C and its management during psychiatric hospitalization. METHODS: 364 hospitalized adults receiving SGAs underwent LDL-C target assessments. Records of patients with above-target LDL-C were searched for dietary or pharmacologic treatments and referrals for medical consultation. RESULTS: Above-target LDL-C levels were present in 100 (27.5%) patients and were associated with higher total cholesterol, lower high-density lipoprotein cholesterol, older age, higher systolic blood pressure, smoking and male gender (r(2): 0.53; p<0.0001). Only 32.0% of these patients received appropriate interventions during hospital stays of 27.6+/-23.3 days. CONCLUSIONS: A substantial number of SGA-treated patients have above-target LDL-C, but do not receive interventions to reduce the risk of CHD.     

Safety and efficacy of the M2A patency capsule for diagnosis of critical intestinal patency: results of a prospective clinical trial

BACKGROUND AND AIM: The presence of a critical intestinal stricture is a contraindication for conventional capsule endoscopy for the risk of impaction. Prior assessment of intestinal patency can substantially minimize this risk. The aim of the present study was to assess the safety and efficacy of the M2A patency capsule (PC) for verification of intestinal strictures. METHODS: The M2A PC consists of a biodegradable body surrounding a small radiofrequency identification (RFID) tag. This capsule was administered to patients with known or suspected intestinal strictures. Patency was verified if the capsule was excreted intact. The capsule disintegrated into small fragments and only the RFID tag was excreted if retained at the stricture beyond a stipulated time. The patency scanner was used to detect the RFID tag externally. The M2A video capsule (VC) was administered to patients who excreted the intact capsule. RESULTS: Twenty-six patients with known or suspected intestinal strictures were administered the M2A PC. This included 16 (61%) patients with tuberculosis, eight (31%) with Crohn's disease, and one each of postoperative and malignant strictures. Eight capsules were excreted intact within 72 h and two at 109 and 110 h. Fifteen capsules disintegrated in the G(I) tract and one capsule was removed during surgery. No PC-related complications were noted. Six of the eight patients who tested positive for patency were tested with the regular M2A VC with normal excretion. CONCLUSION: The M2A PC is a reliable indicator of functional patency in suspected or even known cases of intestinal stricture. It could be used prior to conventional capsule endoscopy to predict and minimize the risk of impaction.