Transfer of normal 99mTc-ECD brain SPET databases between different gamma cameras

A stereotactic, normal perfusion database is imperative for optimal clinical brain single-photon emission tomography (SPET). However, interdepartmental use of normal data necessitates accurate transferability of these data sets. The aim of this study was to investigate transfer of three normal perfusion databases obtained in the same large population of healthy volunteers who underwent sequential scanning using multihead gamma cameras with different resolution. Eighty-nine healthy adults (46 females, 43 males; aged 20-81 years) were thoroughly screened by history, biochemistry, physical and full neurological examination, neuropsychological testing and magnetic resonance imaging. After injection of 925 MBq technetium-99m labelled ethyl cysteinate dimer (ECD) under standard conditions, 101 scans were acquired from all subjects (12 repeat studies) on a triple-head Toshiba GCA-9300A (measured average FWHM 8.1 mm). Ninety-one sequential scans were performed on a dual-head Elscint Helix camera (FWHM 9.6 mm) and 22 subjects also underwent imaging on a triple-head Prism 3000 (FWHM 9.6 mm). Images were transferred to the same processing platform and reconstructed by filtered back-projection with the same Butterworth filter (order 8, cut-off 0.9 cycles/cm) and uniform Sorensen attenuation correction (mu = 0.09). After automated rigid intrasubject registration, all subjects were automatically reoriented to a stereotactic template by a nine-parameter affine transformation. The databases were analysed using 35 predefined volumes of interest (VOIs) with normalisation on total VOI counts. For comparison, the high-resolution data were smoothed with a 3D Gaussian kernel to achieve more similar spatial resolution. Hoffman phantom measurements were conducted on all cameras. Partial volume effects after smoothing varied between -6.5% and 10%, depending on VOI size. Between-camera reproducibility was 2.5% and 2.7% for the Toshiba camera versus the Helix and the Prism database, respectively. The highest reduction in between-camera variability was achieved by resolution adjustment in combination with linear washout correction and a Hoffman phantom-based correction. In conclusion, transfer of normal perfusion data between multihead gamma cameras can be accurately achieved, thereby enabling widespread interdepartmental use, which is likely to have a positive impact on the diagnostic capabilities of clinical brain perfusion SPET.     

Norovirus and foodborne disease, United States, 1991-2000

Efforts to prevent foodborne illness target bacterial pathogens, yet noroviruses (NoV) are suspected to be the most common cause of gastroenteritis. New molecular assays allow for better estimation of the role of NoV in foodborne illness. We analyzed 8,271 foodborne outbreaks reported to the Centers for Disease Control and Prevention from 1991 to 2000 and additional data from 6 states. The proportion of NoV-confirmed outbreaks increased from 1% in 1991 to 12% in 2000. However, from 1998 to 2000, 76% of NoV outbreaks were reported by only 11 states. In 2000, an estimated 50% of foodborne outbreaks in 6 states were attributable to NoV. NoV outbreaks were larger than bacterial outbreaks (median persons affected: 25 versus 15), and 10% of affected persons sought medical care; 1% were hospitalized. More widespread use of molecular assays will permit better estimates of the role of NoV illness and help direct efforts to control foodborne illness.     

Diagnostic and prognostic guidelines for the vegetative and minimally conscious states

Many individuals who sustain severe brain injury experience prolonged or permanent disorders of consciousness. While these disorders may appear homogeneous, important distinctions exist in prognosis and clinical management. Studies suggest, however, that the incidence of diagnostic inaccuracy is high in both acute care and rehabilitation settings. In this paper, we review consensus-based diagnostic and prognostic criteria for the vegetative and minimally conscious states. We also discuss recent developments and future directions for research in this area.     

Paracoccidioidomycosis: an epidemiologic survey in a pediatric population from the Brazilian Amazon using skin tests

Since Paracoccidioides brasiliensis and Histoplasma capsulatum are known to be present in similar environments, there have been many epidemiologic investigations regarding the prevalences of these two organisms. However, cross-reactivity can occur in paracoccidioidin and histoplasmin skin tests, and this usually results in the overestimation of the prevalence of P. brasiliensis.The prevalence of infection with P. brasiliensis was evaluated in a cross-sectional study of 298 asymptomatic school children in the Brazilian Amazon region (Mato Grosso State). In this investigation, the reactivity of children to two different P. brasiliensis antigen preparations, paracoccidioidin and a purified 43-kD glycoprotein (gp43), was compared with or without the co-administration of histoplasmin. In the group of individuals receiving paracoccidioidin who had a positive histoplasmin skin test result, the prevalence of exposure to P. brasiliensis was 44% (16 of 36). This reactivity to P. brasiliensis was significantly higher than that observed in other groups, which ranged from 4% to 6% (P < 5 x 10(-4) for each). Overall prevalence was 4.6% (95% confidence interval = 2.5-7.7%). These data suggest that gp43 provides a better estimate of exposure to P. brasiliensis when the co-administration of histoplasmin is desired.     

Central fatigue and transcranial magnetic stimulation: effect of caffeine and the confound of peripheral transmission failure

In this experiment, we attempt to replicate the fatigue-induced decline in voluntary surface electromyography (EMG) and motor evoked potentials (MEPs) observed in previous studies and determine: (1) if this decline can be attributed to central failure, and (2) whether this failure is offset by caffeine. Seven subjects each attended two sessions (caffeine and placebo). Central excitability was estimated using transcranial magnetic stimulation (TMS), and surface EMG and twitch interpolation were used to estimate voluntary activation before, during and after fatigue of the first dorsal interosseous (FDI). Mass action potentials (M waves) were evoked to assess peripheral transmission throughout the experiment. We observed an increase in post-activation potentiation of the motor evoked potential in the caffeine trial and a fatigue-induced decline in the MEP and maximal EMG in both the placebo and caffeine trials. However, there was also a fatigue-induced decline in peripheral transmission, and estimates of central failure were considerably reduced when normalized to the M wave. A review of central fatigue literature revealed many studies that attribute the decline in voluntary EMG or MEPs wholly to central failure and fail to consider peripheral transmission. Thus, we conclude by stressing the importance of reporting peripheral transmission when surface recordings are used to estimate central mechanisms.     

Activation of fibrinolysis in the pericardial cavity after cardiopulmonary bypass

Aprotinin is frequently administered systemically in patients undergoing cardiopulmonary bypass to preserve platelet function and ameliorate excessive activation of fibrinolysis. More recently, aprotinin topically applied in the pericardial cavity was also found to improve postoperative blood loss. However, platelet activation was not reduced locally during surgery. Hence, we investigated in the present prospective, in a randomized double-blind trial, the intra- and early postoperative state of systemic and local fibrinolytic activity, and whether topically administered aprotinin acts as an antifibrinolytic and therefore improves local hemostasis. Patients undergoing elective coronary artery bypass grafting were divided in two groups containing 22 patients each. Both, group I and II patients received high-dose aprotinin (6.0 x 10(6) kallikrein inhibitor units (KIU)) systemically. Before resuming extracorporeal circulation (ECC), either 1.0 x 10(6) KIU aprotinin (group I) or vehicle solution (group II) was applied into the pericardial cavity. Plasminogen, 2 alpha(2)-antiplasmin, plasmin-alpha(2)-antiplasmin complex, plasminogen-activator-inhibitor type-1 and D-dimers were measured in the pericardial cavity and systemic circulation immediately before resuming extracorporeal circulation (ECC), and at 1 h and 4 h postoperatively. The local fibrinolytic activity was found to significantly exceed that measured in the systemic circulation over time, whether ot not they received aprotinin into the thoracic wound surface. Furthermore, evidence was provided that topically applied aprotinin reduces not only the local fibrinolytic activity but also the postoperative blood loss significantly by 33% which demonstrates the clinical relevance. The local activation of fibrinolysis seems to play an important role in blood loss after cardiopulmonary bypass. Therefore in fibrinolysis and blood coagulation the surgeon should not only consider what happens in the systemic circulation but also on a local level.     

AACR Special Conference: Advances in Breast Cancer Research--Genetics, Biology, and Clinical Implications, Huntington Beach, California, USA, 8-12 October 2003

The recent meeting 'Advances in Breast Cancer Research--Genetics, Biology, and Clinical Implications' was an American Association for Cancer Research (AACR) Special Conference in Cancer Research, for which the underwriting sponsor was the Avon Foundation. Presentations were made from prominent scientists on several relevant basic science and clinic-oriented topics, including mammary stem cells and development, steroid receptors, matrix and stromal-epithelial interactions, oncogene signaling and imaging, genetics and prevention, and molecular therapeutics. A summary of recent findings is presented here, with a particular emphasis on unpublished work.     

Blastocyst development after vitrification of multipronuclear zygotes using the Flexipet denuding pipette

The purpose of this study was to demonstrate the safety and efficacy of vitrification of human pronuclear stage (PN) embryos in the human assisted reproduction laboratory. Using single pronucleate (1PN) and three pronucleate (3PN) zygotes, the impact of vitrification in the Flexipet denuding pipette (FDP) as a carrier was assessed in terms of survival, embryonic development and blastocyst formation when compared according to the PN number, and unvitrified controls. A total of 65 1PN and 152 3PN zygotes were vitrified; after warming 82% (53/65) of 1PN and 90% (137/152) of 3PN survived. The overall percentage of warmed zygotes (1PN and 3PN) that cleaved and reached 2-cell stage did not differ (chi(2); P = 0.32) from the control groups (77%; 147/190 versus 85%; 115/136). In addition, when the cleavage behaviour was examined on day 3 for >or=4-cell stage, no significant differences (chi(2); P = 0.95) were observed between the vitrified group and the unvitrified control groups (74%; 109/147 versus 77%; 89/115). Comparing the developmental potential up to cavitation and blastocyst formation on day 5, the overall outcome of the vitrified PN was 31% compared with 33% for the controls (chi(2); P = 0.76). The simple vitrification protocol used in this study, and these data highlight the usefulness of vitrification using FDP as a consistent and effective cryopreservation method for pronuclear zygotes, and a suitable alternative to slow cryopreservation protocols.     

Inhibition of interleukin-1 but not tumor necrosis factor suppresses neovascularization in rat models of corneal angiogenesis and adjuvant arthritis

OBJECTIVE: To assess the capacities of the cytokine inhibitors interleukin-1 receptor antagonist (IL-1Ra; anakinra) and PEGylated soluble tumor necrosis factor receptor I (PEG sTNFRI; pegsunercept) to suppress neovascularization. METHODS: A corneal angiogenesis assay was performed by implanting nylon discs impregnated with an angiogenic stimulator (basic fibroblast growth factor or vascular endothelial growth factor) into one cornea of female Sprague-Dawley rats. Animals were treated with IL-1Ra or PEG sTNFRI for 7 days, after which new vessels were quantified. In a parallel study, male Lewis rats with mycobacteria-induced adjuvant-induced arthritis were treated with IL-1Ra or PEG sTNFRI for 7 days beginning at disease onset, after which scores for inflammation and bone erosion as well as capillary counts were acquired from sections of arthritic hind paws. RESULTS: Treatment with IL-1Ra yielded a dose-dependent reduction in growth factor-induced corneal angiogenesis, while PEG sTNFRI did not. IL-1Ra, but not PEG sTNFRI, significantly reduced the number of capillaries in arthritic paws, even though both anticytokines reduced inflammation and bone erosion to a similar degree. CONCLUSION: These data support a major role for IL-1, but not TNFalpha, in angiogenesis and suggest that an additional antiarthritic mechanism afforded by IL-1 inhibitors, but not anti-TNF agents, is the suppression of the angiogenic component of pannus.     

NK and trophoblast cells interaction: cytotoxic activity on recurrent pregnancy loss

Abstract

The trial objective was to determine the peripheral blood NK cells cytotoxic activity effect on trophoblast cells at recurrent pregnancy loss (RPL). The investigation involved non-pregnant women with PRL in proliferating and secretory menstrual cycle phases (PMCPh and SMCPh, respectively); women of 6–7 weeks pregnancy with RPL in past medical history; healthy fertile non-pregnant women in PMCPh and SMCPh, women of 6–7 weeks physiological pregnancy, nulliparity healthy women with regular menstrual function in PMCPh and SMCPh. NK cells cytotoxic activity was determined using peripheral blood mononuclear cells. The target cells were JEG-3?line trophoblasts. It has been established that NK cells cytotoxic activity effect on trophoblasts is lower in SMCPh than in PMCPh in non-pregnant fertile women. The NK cells cytotoxic activity was higher in SMCPh than in PMCPh in non-pregnant women with PRL and also higher than the same value in SMCPh in non-pregnant fertile women. The increased NK cells cytotoxic activity values in SMCPh in women with RPL may be the reason for miscarriage.