Utility of sonographically guided biopsy in metabolically suspected recurrent lymphoma.

OBJECTIVE: The purpose of this study was to determine the diagnostic accuracy of sonographically guided biopsy of [(18)F]fluorodeoxyglucose (FDG)-avid foci on positron emission tomography (PET)/computed tomography (CT) in patients with lymphoma. METHODS: We retrospectively reviewed the medical records of 56 patients with lymphoma (25 male and 31 female; mean age, 48.5 years; range, 22-80 years) who underwent sonographically guided biopsy of hypermetabolic FDG-avid foci precisely localized by PET/CT. Biopsies were performed up to 3 months after PET/CT. The accuracy of core biopsy was calculated and compared with clinical follow-up and histopathologic results of open biopsy. RESULTS: Sixty-six sonographically guided biopsies were performed in the 56 patients. Histopathologic results were conclusive in 53 (80%) of 66. No complications occurred during or after the procedure. The overall sensitivity, specificity, positive predictive value, and accuracy for diagnosis of lymphoma were 100%, 95%, 97%, and 98%, respectively. CONCLUSIONS: Sonographically guided biopsy is a safe and effective means for investigating metabolically active lesions on FDG-PET/CT in patients with known lymphoma.     

Major histocompatibility complex (MHC) tetramer technology: an evaluation

Single-cell assays are currently favored to quantitate T-cell responses. Staining antigen-specific T-cells with fluorescently labeled tetrameric major histocompatibility complex (MHC)/peptide complexes has greatly enhanced the ability to assess the cellular dynamics of an immune response at the single-cell level. This article reviews MHC tetramer technology, defining it, discussing how MHC tetramers are made, outlining the benefits of this technology, comparing and contrasting it to other methods for evaluating immune responses, and describing current applications.     

Neurodevelopmental outcome of children with intrauterine growth retardation: a longitudinal, 10-year prospective study

One hundred twenty-three children with intrauterine growth retardation were prospectively followed from birth to 9 to 10 years of age in order to characterize their specific neurodevelopmental and cognitive difficulties and to identify clinical predictors of such difficulties. Perinatal biometric data and risk factors were collected. Outcome was evaluated at age 9 to 10 by neurodevelopmental, cognitive, and school achievement assessments. Sixty-three children served as controls who were appropriate for gestational age. Significant differences in growth (P < .001), neurodevelopmental scores (P < .001), intelligence quotient (IQ) (P < .0001), and school achievements measured by the Kaufmann Assessment Battery for Children (P < .001) were found between the children with intrauterine growth retardation and controls. Children with intrauterine growth retardation demonstrated a specific profile of neurocognitive difficulties at school age, accounting for lower school achievements. The best perinatal parameter predictive of neurodevelopment and IQ was the Cephalization Index (P < .001). Somatic catch-up growth at age 2 and at age 9 to 10 correlated with favorable outcome at 9 to 10 years of age.     

Lymphocyte resistance to lysophosphatidylcholine mediated apoptosis in atherosclerosis

OBJECTIVE: Apoptosis is being increasingly regarded as a key component in the development and progression of atherosclerosis. Since it has become apparent that the immune system plays a predominant role in mediating atherogenesis, there has been a growing recognition that the evaluation of lymphocyte apoptosis may contribute to understanding a persistent altered immune and inflammatory response. The aim of the present study was to evaluate the apoptotic effect of lysophosphatidylcholine (LPC) on peripheral blood lymphocytes (PBL) derived from unstable angina (UA) patients, as compared to healthy donors. METHODS: PBL isolated from 27 healthy donors and 25 age matched UA patients were examined. Early apoptotic events induced by LPC in resting and phytohemagglutinin (PHA)-activated lymphocytes were evaluated by several apoptotic assays. The levels of intracellular reactive oxygen species (ROS) and the expression of apoptotic regulated proteins (Bcl-2 and Bax) were measured. RESULTS: LPC was found to induce apoptosis in normal activated lymphocytes, in a dose- and time-dependent manner, in association with an increase in intracellular ROS. In UA patients, an exposure of PHA-activated PBL to LPC triggered neither an increase in ROS generation, nor in the apoptotic manifestations, and was associated with a significantly lower ratio of Bax/Bcl-2 expression. CONCLUSION: Our results indicate that PBL isolated from UA patients may be resistant to apoptosis induction by LPC, resulting from oxidative stress challenge and dysregulation of apoptosis-related protein expression.     

A hybrid algorithm for PET/CT image merger in hybrid scanners

Purpose To improve the PET image quality of a hybrid PET/CT scanner by merging CT borders with PET texture. PET/CT scanners provide both high-resolution CT images showing anatomical details and PET images of low-resolution physiological information about radiopharmaceutical uptake. Standard smoothing of noisy PET images may further impair PET resolution, reducing small lesion detectability. Methods The CT edge data and the PET texture data were merged using a modified form of an algorithm called HCT (hybrid computed tomography). In merged PET/CT images, each PET pixel value was estimated by iteratively applying a corrected 2D Taylor expansion to each of its eight neighbors. The spatial derivative term was used only near anatomical edges provided by the CT. This counts-preserving algorithm was tested on a special resolution phantom and patient data sets obtained by PET/CT acquisitions. Results The HCT algorithm provided phantom PET images with sharp borders and improved resolution (≤3 mm as compared to ≥4 mm). HCT increased the signal to background contrast ratios by an average of 61% (40–89%) while maintaining noise reduction similar to the Gaussian filtering standard in PET. In the clinical PET images, HCT allowed for an improved delineation of pulmonary and pelvic lesions and an improved visualization of the brain. Conclusion A new reconstruction algorithm for merging CT anatomical edge data with functional PET data has been introduced. The algorithm smoothes noisy PET images while retaining sharper edges at corresponding anatomical borders, resulting in an improvement in resolution and contrast ratio.     

Genetic modulation of apoptotic pathways fails to alter disease course in tripeptidyl-peptidase 1 deficient mice

Late-infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal, incurable neurodegenerative disease of children caused by the loss of the lysosomal protein tripeptidyl-peptidase 1 (TPP1). Previous studies have suggested that Bcl-2-dependent apoptotic pathways are involved in neuronal cell death in LINCL patients and, as a result, anti-apoptotic treatments that increase Bcl-2 activity have been proposed as a potential therapeutic approach. In this study, we have directly investigated whether targeting anti-apoptotic pathways may be of value in LINCL in a mouse model of this disease that lacks TPP1 and which recapitulates many aspect of the human disease, including a greatly shortened life-span. Our approach was to genetically modify apoptotic pathways and determine the effects of these changes on the severe neurodegenerative phenotype of the LINCL mouse. LINCL mice were generated that either lacked the pro-apoptotic p53 or had increased levels of anti-apoptotic Bcl-2, changes that would exacerbate or ameliorate neuronal death, respectively, should pathways involving these proteins be important. Neither modification affected the shortened life-span of the LINCL mouse. These results suggest that either neuronal death in LINCL does not occur via apoptosis or that it occurs via apoptotic pathways not involving p53 or Bcl-2. Alternatively, pathways involving p53 and/or Bcl-2 may be involved in neuronal death under normal circumstances but may not be the only routes to this end. Importantly, our findings suggest that targeting pathways of cell death involving p53 or Bcl-2 do not represent useful directions for developing effective treatment.     

Absence of TGFBR2 mutations in patients with spontaneous spinal CSF leaks and intracranial hypotension

A heritable connective-tissue-disorder often is suspected in patients with spontaneous spinal CSF leaks and intracranial hypotension, but the nature of the disorder remains unknown in most patients. The aim of this study was to assess the gene encoding TGF-β receptor-2 (TGFBR2) as a candidate gene for spinal CSF leaks. We searched the TGFBR2 gene for mutations in eight patients with spontaneous spinal CSF leaks who also had other features associated with TGFBR2 mutations, i.e., skeletal features of Marfan syndrome, arterial tortuosity, and(or) thoracic aortic aneurysm. The mean age of these 7 women and 1 man was 38 years (range 14–60 years). We detected no TGFBR2 mutations and conclude that TGFBR2 mutations are not a major factor in spontaneous spinal CSF leaks.     

Prostate cancer in fathers with fewer male offspring: the Jerusalem Perinatal Study cohort

Recent studies have suggested the involvement of loci on the Y chromosome in prostate cancer. We studied the relative risk (RR) of prostate cancer in relation to sex ratio of offspring in a cohort of 38,934 Israeli men who were followed from the birth of their offspring (in 1964 through 1976) until 2005. Cox models were used to adjust for changes in incidence over time, age, the man's year of birth, and social and ethnic variables. A total of 712 men were diagnosed with prostate cancer. Compared with men who had at least one son, men with only daughters had an increased risk of prostate cancer (adjusted RR = 1.40, 95% confidence interval [CI] = 1.20 to 1.64, P<.0001). In men with one, two, or three or more offspring, the relative risks associated with absence of sons were 1.25 (95% CI = 1.00 to 1.56), 1.41 (95% CI = 1.04 to 1.91), and 1.60 (95% CI = 1.05 to 2.43), respectively. Men with no daughters showed no statistically significantly altered risk, compared with men who had offspring of both sexes. The relative risk of prostate cancer decreased as the number of sons increased (P(trend)<.0001) but did not change with the number of daughters. These findings suggest that a Y chromosome locus may be involved in prostate cancer risk in this population.