Sensitivity and interrater agreement of CT and diffusion-weighted MR imaging in hyperacute stroke

BACKGROUND AND PURPOSE: Previous acute stroke studies found diffusion-weighted (DW) imaging superior to CT for detection of early ischemic signs (EIS). However, these findings were confounded by a large time interval in favor of DW imaging. We compared DW images and CT scans obtained with a short time delay in patients with acute stroke to define the sensitivity and interrater agreement of both imaging techniques. METHODS: CT scans and DW images were obtained within 6 hours of symptom onset in 46 patients with acute stroke. Three neuroradiologists and three neurologists reviewed the images for EIS in five regions of the middle cerebral artery (MCA) territory and estimated the extent of EIS (< or > one-third of the MCA territory). RESULTS: The mean delay between imaging with both modalities was 24.5 minutes (range, 10-41 minutes). Forty-five of 46 patients had an ischemic stroke. EIS were seen on 33 of 45 CT scans (73% sensitivity; 95% confidence interval [CI]: 58-85%) and on 42 of 45 DW images (93% sensitivity; 94% CI: 82-99%). Interrater agreement was moderate (kappa = 0.57) for CT and excellent (kappa = 0.85) for DW imaging. CT studies had a moderate interrater agreement for estimation of EIS greater than one-third of the MCA territory (kappa = 0.40), whereas DW imaging showed good results (kappa = 0.68). Sensitivity for detection of greater than one-third of the MCA territory was equally poor (57%, 95% CI: 29-82%) for both CT and DW imaging. CONCLUSION: DW imaging helped identify EIS with higher sensitivity than that of CT. The interrater variability of the one-third rule was high for CT, and thus the clinical applicability of CT is limited. Our results support the application of stroke MR imaging for the treatment of patients with acute stroke.     

Low-volume resuscitation with a polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201) provides adequate tissue oxygenation for survival in a porcine model of controlled hemorrhage

BACKGROUND: We have shown in a previous work that HBOC-201 is able to reverse anaerobic metabolism at low volumes in a porcine model of controlled hemorrhage. On the basis of these results, we hypothesize that low-volume resuscitation with HBOC-201 in a porcine model of controlled hemorrhage provides adequate tissue oxygenation to limit end-organ damage and allow for survival of the animal. METHODS: Twenty-four Yorkshire swine (55-65 kg) were rapidly hemorrhaged to a mean arterial pressure (MAP) of 30 mm Hg, maintained hypotensive for 45 minutes, and then divided into four groups. The first group, Shed Blood (BL), was resuscitated with shed blood to baseline MAP. A second group, Shed Blood (60), underwent resuscitation for four hours at an MAP of 60 mm Hg with shed blood. The third group, LR + Blood, was resuscitated with lactated Ringer's (maximum, 40 mL/kg) followed by shed blood to baseline MAP. The final group, HBOC (60), underwent resuscitation for 4 hours at an MAP of 60 mm Hg with HBOC-201. Hemodynamic variables, urine output, blood gas analyses, lactate levels, and jejunal oximetry were followed throughout the experiment. Animals were allowed to survive and underwent necropsy on postinjury day 3. Histologic comparisons were made. Data were analyzed using analysis of variance/Duncan's multiple range test. RESULTS: All animals survived the hemorrhage/resuscitation. One animal in the LR + Blood group died on postinjury day 1. Heart rate, MAP, and arterial pH were similar between groups. Cardiac output was significantly lower throughout resuscitation in the HBOC (60) group. Jejunal oximetry was similar throughout the experiment in all groups, revealing a decline in Po2 during hemorrhage and return to baseline or near baseline during resuscitation. There was no evidence of renal dysfunction. Histologically, one animal in the LR + Blood group and four of six animals in the HBOC (60) group demonstrated mild hepatocellular damage. All other tissues examined were found to have no significant abnormalities. Elevations in serum aspartate aminotransferase levels were noted when comparing the HBOC (60) group to the Shed Blood (BL) and Shed Blood (60) groups on day 2. Significant decreases in hemoglobin levels were noted in the HBOC (60) group compared with all other groups beginning on day 2. CONCLUSION: Low-volume resuscitation with HBOC-201 provides adequate tissue oxygenation for survival in a porcine model of controlled hemorrhagic shock with no long-term organ dysfunction identified. Although some animals did show mild hepatocellular damage with elevations of aspartate aminotransferase at day 2, these findings did not appear to have clinical relevance, and the enzyme elevations were trending toward normal by the third postoperative day. Decreases in hemoglobin levels at the later time points were expected, given the half-life of the product.     

Autologous adjuvant linked fibroblasts induce anti-glioma immunity: implications for development of a glioma vaccine

Summary Objectives: Adjuvant-linked vaccines have been shown to induce anti-tumor immunity in patients with a variety of solid tumors. In this study we describe anin vitro model of active immunotherapy using autologous fibroblasts as immunogen. Correlative results from glioma patients immunized with autologous fibroblasts are also described. Methods: Peripheral blood lymphocytes (PBLs) from normal subjects were immunizedin vitro against autologous skin fibroblasts coupled to the adjuvant muramyl dipeptide. The lymphocytes developed cell-mediated cytotoxicity that was measured with a short-term chromium release assay. Results ofin vitro experiments were compared to data derived from glioma patients immunized with subcutaneous injection of an autologous adjuvantlinked fibroblast vaccine. Glioma target cells and fibroblast immunogens were derived from early passage primary tissue culture. Results: A comparison of autologous vs. homologous immunogen indicated that major histocompatibility complex matching was required at the sensitization stage of immunity (17.2±3.4% specific lysis vs. 0.4±3.1%,P<0.01). Pre-treatment of fibroblast immunogen cells with interferon gamma (IFN-γ) was found to significantly increase immunity (42.2±10.0%,P<0.01), as did IFN-γ pre-treatment of tumor target cells (35.8±9.0%,P<0.01). The positive effect of IFN-γ was diminished by treatment of cells with IFN-α. Thesein vitro results correlated well within vivo data derived from glioma patients immunized with an autologous adjuvant-linked fibroblast vaccine. PBLs from patients developed direct cell-mediated cytotoxicity against autologous tumor cells. Lysis of tumor targets afterin vivo immunization increased over a three-week interval (from 1.2 ± 3.0% to 21.0 ± 3.4%,P < 0.01) while lysis of a non-MHC matched control cell line remained essentially unchanged. Conclusions: Specific lysis of glioma targetsin vitro was achieved afterin vivo sensitization with autologous adjuvant-linked fibroblasts. Collectively, the data indicate that biochemically modified autologous cells can stimulate anti-glioma immunity in humans. The degree of specific immunity seen in our patients compares favorably with other published series using glioma cells as an antigenic source. Accordingly, fibroblasts may represent a practical alternative to glioma cells for vaccine construction.     

The degree of depression in Hamilton rating scale is correlated with the density of presynaptic serotonin transporters in 23 patients with Wilson's disease

Objective: One of the most frequent psychiatric symptoms in patients with Wilson's disease (WD) is depression. It has been suggested that depression is associated with deficits in serotonergic neurotransmission, but, hitherto, no measurements have been performed in WD. Methods: We prospectively examined 23 adult patients (12 women, 11 men, mean age 40 years) with WD for symptoms of depression using the Hamilton rating scale for depression (HAMD). We correlated the data with the presynaptic serotonin transporter density (SERT density) in the thalamus–hypothalamus and the midbrain–pons regions measured with high resolution single-photon emission computed tomography (SPECT) 24 hours after the application of 180 MBq 2β-carbomethoxy-3β-(4 [¹²³I]iodophenyl)tropane ( [¹²³I]b-CIT). The regions of interest were determined by coregistration with a standard MRI dataset. Results: A significant negative correlation was found between HAMD and SERT density in the thalamus–hypothalamus region (r = −0.49, p = 0.02), but not in the midbrain–pons (r = −0.31, p = 0.15). Conclusions: We conclude that depression in patients with Wilson's disease is correlated with alterations of serotonergic neurotransmission in the thalamus–hypothalamus region. Received: 24 July 2002, Received in revised form: 20 November 2002, Accepted: 28 November 2002 Correspondence to Wieland Hermanns, MD     

Dietary fat, body weight, and cancer: contributions of studies in rodents to understanding these cancer risk factors in humans

Understanding diet and energy balance as risk factors for breast, colon, and other cancers requires information on the contribution of each factor and of interactions among factors to cancer risk. Rodent models for breast cancer provide extensive data on effects of dietary fat and calories, energy balance, body weight gain, and physical activity on tumor development. Analyses of the combined data from many studies have shown clearly that quality and quantity of dietary fat and energy balance contribute independently to increased mammary gland tumorigenesis. These findings were seen in female rats fed diets high in fat (35-40% of calories) compared to rats fed control diets, with approximately 10% of calories as fat (Fay and Freedman, 1997, Breast Cancer Res. Treat. 46, 215-223). The methods used permit comparison of experimental and epidemiological data, and they may be useful in extrapolating between species and developing public health recommendations. In addition to the contributions of lifetime-diet composition, intake, energy balance, and physical activity to cancer risk, there are questions about the timing and duration of alterations in these factors and about the "dose-response" characteristics of cancer risk to the factors. Endocrine mechanisms may be significant in mammary gland tumor risk, but experimental and epidemiological data indicate that cancers at other sites, such as colon and liver, also are influenced by the factors listed. Other diet and lifestyle factors that influence energy, or specifically fat, metabolism may also affect risk for cancers that are promoted by increased intake of fat and calories. Studies of separate and interactive effects of dietary fat, black tea, weight gain, and mammary gland tumorigenesis (Rogers, et al, 1998, Carcinogenesis 19, 1269-1273) have been analyzed. Using adjustment of carcinogenesis endpoints for body weight, tumor burden, and latency, they were found to be related to weight gain within treatment groups in 2 of 3 experiments.      

Repeated exposure of rats to JP-4 vapor induces changes in neurobehavioral capacity and 5-HT/5-HIAA levels

Thirty-two Sprague-Dawley rats were exposed for 6 h/d for 14 consecutive days to JP-4 jet fuel vapor (2 mg/L) or room air control conditions. Following a 14- or 60-d recovery period, rats completed a battery of 8 tests selected from the Navy Neurobehavioral Toxicity Assessment Battery (NTAB) to evaluate changes in performance capacity. Exposure to JP-4 vapor resulted in significant changes in neurobehavioral capacity on several tests that varied as a function of the duration of the recovery period. Rats were evaluated for major neurotransmitter and metabolite levels in five brain regions and in the blood serum. Levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were shown to be significantly elevated in several brain regions as well as in the blood serum in the vapor-exposed groups. Results of the rat study are compared to previously reported neurobehavioral evaluations of European manufacturing personnel exposed chronically to jet fuel vapor.     

Successful pregnancy in transfusion-dependent thalassaemia

Successful pregnancy in a transfusion-dependent thalassaemic patient receiving subcutaneous desferrixaomine is reported. This is the first such case to be described.