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F G Blankenberg

Publications and source records attributed to F G Blankenberg.

At least 37 records · Page 2Linked to original sources
PubMed2000

Sonography, CT, and MR imaging: a prospective comparison of neonates with suspected intracranial ischemia and hemorrhage.

BACKGROUND AND PURPOSE: Sonography, CT, and MR imaging are commonly used to screen for neonatal intracranial ischemia and hemorrhage, yet few studies have attempted to determine which imaging technique is best suited for this purpose. The goals of this study were to compare sonography with CT and MR imaging prospectively for the detection of intracranial ischemia or hemorrhage and to determine the prognostic value(s) of neuroimaging in neonates suspected of having hypoxic-ischemic injury (HII). METHODS: Forty-seven neonates underwent CT (n = 26) or MR imaging (n = 24) or both (n = 3) within the first month of life for suspected HII. Sonography was performed according to research protocol within an average of 14.4 +/- 9.6 hours of CT or MR imaging. A kappa analysis of interobserver agreement was conducted using three independent observers. Infants underwent neurodevelopmental assessment at ages 2 months (n = 47) and 2 years (n = 26). RESULTS: CT and MR imaging had significantly higher interobserver agreement (P < .001) for cortical HII and germinal matrix hemorrhage (GMH) (Grades I and II) compared with sonography. MR imaging and CT revealed 25 instances of HII compared with 13 identified by sonography. MR imaging and CT also revealed 10 instances of intraparenchymal hemorrhage (>1 cm, including Grade IV GMH) compared with sonography, which depicted five. The negative predictive values of neuroimaging, irrespective of technique used, were 53.3% and 58.8% at the 2-month and 2-year follow-up examinations, respectively. CONCLUSION: CT and MR imaging have significantly better interobserver agreement for cortical HII and GMH/intraventricular hemorrhage and can reveal more instances of intraparenchymal hemorrhage compared with sonography. The absence of neuroimaging findings on sonograms, CT scans, or MR images does not rule out later neurologic dysfunction.

Brain↗
PubMed1999

Non-invasive diagnosis of acute heart- or lung-transplant rejection using radiolabeled annexin V.

BACKGROUND: Apoptosis is a ubiquitous set of cellular processes by which superfluous or unwanted cells are eliminated in the body without harming adjacent healthy tissues. When apoptosis is inappropriate (too little or too much), a variety of human diseases can occur, including acute heart or lung transplant rejection. OBJECTIVE: Our group has developed a new radiopharmaceutical, radiolabeled annexin V, which can image apoptosis. RESULTS AND CONCLUSION: Here we briefly review the biomolecular basis of apoptosis and its role in acute rejection. We also describe the possible use of radiolabeled annexin V to screen children noninvasively for acute rejection following organ transplantation.

Acute Disease↗
PubMed1999

Technetium-99m HYNIC-annexin V: a potential radiopharmaceutical for the in-vivo detection of apoptosis.

Either inadequate or excessive apoptosis (programmed cell death) is associated with many diseases. A method to image apoptosis in vivo, rather than requiring histologic evaluation of tissue, could assist with therapeutic decision making in these disorders. Programmed cell death is associated with a well-choreographed series of events resulting in the cessation of normal cell function, and the ultimate disappearance of the cell. One component of apoptosis is signaling adjacent cells that this cell is committing suicide by externalizing phosphatidylserine to the outer leaflet of the cell membrane. Annexin V, a 32-kDa endogenous human protein, has a high affinity for membrane-bound phosphatidylserine. We have coupled annexin V with the bifunctional hydrazinonicotinamide reagent (HYNIC) to prepare technetium-99m HYNIC-annexin V and demonstrated localization of radioactivity in tissues undergoing apoptosis in vivo. In this report we describe the results of a series of experiments in mice and rats to characterize the biologic behavior of (99m)Tc-HYNIC- annexin V. Biodistribution studies were performed in groups of rats at 10-180 min after intravenous injection of (99m)Tc-HYNIC-annexin V. In order to estimate the degree of apoptosis required for localization of (99m)Tc-annexin V in vivo, mice were treated with dexamethasone at doses ranging from 1 to 20 mg/kg, 5 h prior to (99m)Tc-HYNIC-annexin V administration, to induce thymic apoptosis. Thymus was excised 1 h after radiolabeled HYNIC-annexin V injection; thymocytes were isolated, incubated with Hoechst 33342 followed by propidium iodide, and analyzed on a fluorescence-activated cell sorter. Each sorted cell population was counted in a scintillation counter. To test (99m)Tc-HYNIC-annexin V as a tracer for external radionuclide imaging of apoptotic cell death, radionuclide imaging of Fas-defective mice (lpr/lpr mice) and wild-type mice treated with the antibody to Fas (anti-Fas) was carried out 1 h post injection. Rat biodistribution studies demonstrated a blood clearance half-time of less than 10 min for (99m)Tc-HYNIC-annexin V. The kidneys had the highest concentration of radioactivity at all time points. Studies in the mouse thymus demonstrated a 40-fold increase in (99m)Tc-HYNIC-annexin V concentration in apoptotic thymocytes compared with the viable cell population. A correlation of r=0.78 was found between radioactivity and flow cytometric and histologic evidence of apoptosis. Imaging studies in the lpr/lpr and wild-type mice showed a substantial increase of activity in the liver of wild-type mice treated with anti-Fas, while there was no significant change, irrespective of anti-Fas administration, in lpr/lpr mice. Excellent images of hepatic apoptosis were obtained in wild-type mice 30 min after injection of (99m)Tc-HYNIC-annexin V. The imaging results were consistent with histologic analysis in these animals. In conlusion, these studies confirm the value of (99m)Tc-HYNIC-annexin V uptake as a marker for the detection and quantification of apoptotic cells in vivo.

Animals↗
PubMed1999

Imaging of apoptosis (programmed cell death) with 99mTc annexin V.

UNLABELLED: Apoptosis (programmed cell death) is a critical element in normal physiology and in many disease processes. Phosphatidylserine (PS), one component of cell membrane phospholipids, is normally confined to the inner leaflet of the plasma membrane. Early in the course of apoptosis, this phospholipid is rapidly exposed on the cell's outer surface. Annexin V, an endogenous human protein, has a high affinity for membrane-bound PS. This protein has been labeled with fluorescein and has been used to detect apoptosis in vitro. We describe the use of radiolabeled annexin V to detect apoptosis in vivo. The results are compared to histologic and flow cytometric methods to identify cells and tissues undergoing apoptosis. METHODS: Annexin V was coupled to hydrazinonicotinamide (HYNIC) and radiolabeled with 99mTc. Bioreactivity of 99mTc-HYNIC annexin V was compared with fluorescein isothiocyanate (FITC)-labeled annexin V in cultures of Jurkat T-cell lymphoblasts and in ex vivo thymic cell suspensions undergoing apoptosis in response to different stimuli. In addition, the uptake of FITC annexin V and 99mTc-HYNIC annexin V was studied in heat-treated necrotic Jurkat T-cell cultures. In vivo localization of annexin V was studied in Balb/c mice injected with 99mTc-HYNIC annexin V before and after induction of Fas-mediated hepatocyte apoptosis with intravenously administered antiFas antibody. RESULTS: Membrane-bound radiolabeled annexin V activity linearly correlated to total fluorescence as observed by FITC annexin V flow cytometry in Jurkat T-cell cultures induced to undergo apoptosis in response to growth factor deprivation (N = 10, r2 = 0.987), antiFas antibody (N = 8, r2 = 0.836) and doxorubicin (N = 10, r2 = 0.804); and in ex vivo experiments on thymic cell suspensions with dexamethasone-induced apoptosis from Balb/c mice (N = 6, r2 = 0.989). Necrotic Jurkat T-cell cultures also demonstrated marked increases in radiopharmaceutical (4000-5000-fold) above control values. AntiFas antibody-treated Balb/c mice (N = 6) demonstrated a three-fold rise in hepatic uptake of annexin V (P < 0.0005) above control (N = 10), identified both by imaging and scintillation well counting. The increase in hepatic uptake in antiFas antibody-treated mice correlated to histologic evidence of fulminant hepatic apoptosis. CONCLUSION: These data suggest that 99mTc-HYNIC annexin V can be used to image apoptotic and necrotic cell death in vivo.

Animals↗
PubMed1998

In vivo detection and imaging of phosphatidylserine expression during programmed cell death.

One of the earliest events in programmed cell death is the externalization of phosphatidylserine, a membrane phospholipid normally restricted to the inner leaflet of the lipid bilayer. Annexin V, an endogenous human protein with a high affinity for membrane bound phosphatidylserine, can be used in vitro to detect apoptosis before other well described morphologic or nuclear changes associated with programmed cell death. We tested the ability of exogenously administered radiolabeled annexin V to concentrate at sites of apoptotic cell death in vivo. After derivatization with hydrazinonicotinamide, annexin V was radiolabeled with technetium 99m. In vivo localization of technetium 99m hydrazinonicotinamide-annexin V was tested in three models: fuminant hepatic apoptosis induced by anti-Fas antibody injection in BALB/c mice; acute rejection in ACI rats with transplanted heterotopic PVG cardiac allografts; and cyclophosphamide treatment of transplanted 38C13 murine B cell lymphomas. External radionuclide imaging showed a two- to sixfold increase in the uptake of radiolabeled annexin V at sites of apoptosis in all three models. Immunohistochemical staining of cardiac allografts for exogenously administered annexin V revealed intense staining of numerous myocytes at the periphery of mononuclear infiltrates of which only a few demonstrated positive apoptotic nuclei by the terminal deoxynucleotidyltransferase-mediated UTP end labeling method. These results suggest that radiolabeled annexin V can be used in vivo as a noninvasive means to detect and serially image tissues and organs undergoing programmed cell death.

Animals↗
PubMed1998

The use of technetium Tc 99m annexin V for in vivo imaging of apoptosis during cardiac allograft rejection.

OBJECTIVE: Apoptosis, or programmed cell death, has been suggested as a mechanism of immunologic injury during cardiac allograft rejection. We tested the hypothesis that technetium Tc 99m annexin V, a novel radiopharmaceutical used to detect apoptosis, can be used to detect cardiac allograft rejection by nuclear imaging. METHODS: Untreated ACI rats served as recipients of allogeneic PVG rat (n = 66) or syngeneic ACI rat (n = 30) cardiac grafts. Untreated recipient animals underwent 99mTc-annexin V imaging daily for 7 days. Region of interest analysis was used to quantify the uptake of 99mTc-annexin V. Immediately after imaging grafts were procured for histopathologic analysis and terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick-end labeling of apoptotic nuclei. One group was treated with 10 mg/kg/d cyclosporine (INN: ciclosporin) commencing on day 4 after transplantation (n = 6). RESULTS: Untreated allografts showed histologic signs of rejection 4 days after transplantation. Apoptotic nuclei could be demonstrated in myocytes, endothelial cells, and graft-infiltrating cells of all rejecting allografts. Nuclear imaging revealed a significantly greater uptake of 99mTc-annexin V in rejecting allogeneic grafts than in syngeneic grafts on day 4 (P = .05), day 5 (P < .001), day 6 (P < .001), and day 7 (P = .013) after transplantation. A correlation between the histologic grade of acute rejection and uptake of 99mTc-annexin V was observed (r2 = 0.87). After treatment of rejection with cyclosporine, no apoptotic nuclei could be identified in allografts and uptake of 99mTc-annexin V decreased to baseline. CONCLUSIONS: Apoptosis occurs during acute cardiac allograft rejection and disappears after treatment of rejection. 99mTc-annexin V can be used to detect and monitor cardiac allograft rejection.

Animals↗
PubMed1997

Quantitative analysis of apoptotic cell death using proton nuclear magnetic resonance spectroscopy.

Quantification of apoptotic cell death in vivo has become an important area of investigation in patients with acute lymphoblastic leukemia (ALL). We have devised a noninvasive analytical method to estimate the percentage of apoptotic lymphoblasts in doxorubicin-treated Jurkat T-cell ALL cultures, using proton nuclear magnetic resonance spectroscopy (1H NMR). We have found that the ratio of the methylene (CH2) resonance (at 1.3 ppm) to the methyl (CH3) resonance (at 0.9 ppm) signal intensity, as observed by 1H NMR, is directly proportional to the percentage of apoptotic lymphoblasts in vitro. The correlation between the CH2/CH3 signal intensity ratio and the percentage of apoptotic lymphoblasts was optimal 24 to 28 hours after doxorubicin treatment (r2 = .947, N = 27 samples). There was also a direct temporal relationship between an increase in the CH2/CH3 signal intensity ratio and the onset of apoptosis as detected by nuclear morphologic analysis, fluorescein-annexin V flow cytometry, and DNA gel electrophoresis. Thin-layer chromatography confirmed that a dynamic and/or compositional change of the plasma membrane, rather than increases in lipase activity or fatty acid production, appears to account for the increase in the CH2/CH3 signal intensity ratio during apoptosis. 1H NMR may have clinical utility for the early noninvasive assessment of chemotherapeutic efficacy in patients with ALL.

Annexin A5↗
PubMed1997

Impaired cerebrovascular autoregulation after hypoxic-ischemic injury in extremely low-birth-weight neonates: detection with power and pulsed wave Doppler US.

PURPOSE: To evaluate regional cerebral blood flow with power and pulsed wave Doppler ultrasound (US) in extremely low-birth-weight neonates with periventricular leukomalacia (PVL), germinal matrix hemorrhage (GMH), or both. MATERIALS AND METHODS: The lenticulostriate arteries of 17 preterm neonates (birth weight < or = 1,100 g) were assessed daily with Doppler US during the first 5-6 days of life. The mean arterial pressure and bilateral peak velocity, resistive index, coronal vascular cross-sectional area, and product of the peak velocity and vascular cross-sectional area were measured. RESULTS: Five neonates developed PVL, GMH, or both; results of follow-up examinations in 11 patients were normal. One neonate with severe intrauterine growth retardation and renal tubular acidosis was excluded. Neonates with PVL, GMH, or both showed significantly greater mean values and more variable values of vascular cross-sectional area and product of peak velocity and cross-sectional area than neonates without PVL or GMH (P < .025). Mean resistive index was significantly lower in neonates with PVL, GMH, or both than in neonates without (P < .01). There were no significant differences between mean arterial pressure in neonates with and those without PVL, GMH, or both. CONCLUSION: By enabling the detection of autoregulatory fluctuations in cerebral blood flow associated with hypoxic-ischemic injury, power and pulsed wave Doppler US may enable identification of preterm neonates who are at risk of developing PVL, GMH, or both during the 1st week of life.

Blood Flow Velocity↗
PubMed1996

Detection of apoptotic cell death by proton nuclear magnetic resonance spectroscopy.

Cells undergoing apoptosis (programmed cell death) display profound morphologic and biochemical changes in the nucleus, cytoplasm, and plasma membrane. We have shown a direct temporal relationship between the onset of apoptosis in Jurkat T-cell lymphoblast cultures and a greater than two-fold increase in the signal intensity of the methylene resonance (at 1.3 ppm) as observed by proton nuclear magnetic resonance spectroscopy (1H NMR). The increase in the methylene resonance intensity was seen when apoptosis was induced by serum deprivation, glucocorticoid, and doxorubicin treatment but not in necrotic (nonapoptotic) cell death. We have found similar changes in a variety of other cell lines undergoing apoptosis including the Hut 78 T-cell leukemia, JY natural killer T-cell leukemia, Daudi B-cell lymphoma, HeLa, and 3T3 fibroblast cell lines. Furthermore, this spectral change was diminished in Bcl-2 overexpressing HL-60 cell cultures treated with doxorubicin, which were relatively resistant to apoptosis, as compared to apoptotic HL-60 cultures. 1H NMR spectroscopy therefore may be useful in detecting apoptotic cell death in vivo.

3T3 Cells↗
PubMed1996

Neonatal intracranial ischemia and hemorrhage: diagnosis with US, CT, and MR imaging.

PURPOSE: To assess the usefulness of ultrasound (US), computed tomography (CT), and magnetic resonance (MR) imaging in the detection of intracranial hemorrhage and ischemia in newborns. MATERIALS AND METHODS: Seventy-six neonates who underwent US within 72 hours of CT or MR examination were studied. Four observers rated images for the presence of germinal matrix hemorrhage (GMH), intraventricular hemorrhage (IPH), extraaxial hemorrhage, and hypoxic-ischemic encephalopathy. RESULTS: In 39% of neonates, CT and MR imaging provided greater confidence than US for the diagnosis or exlusion of neonatal ischemia or hemorrhage. Kappa analysis revealed significantly better interobserver agreement with CT than with US for the detection of GMH, IVH, IPH, and cortical infarction or ischemia (P <.005). Interobserver agreement was significantly better with MR imaging than with US for the detection of GMH, IVH, and cortical infarction or ischemia (P < .005). CONCLUSION: Sensitivity and interobserver agreement are better with MR imaging and CT than with US for the detection of neonatal cortical ischemia or infarction.

Apgar Score↗
PubMed1995

Evolving asymmetric hypertrophic pyloric stenosis associated with histologic evidence of eosinophilic gastroenteritis.

The most frequently occurring and important cause of gastric outlet obstruction in the neonate and young infant is infantile hypertrophic pyloric stenosis (IHPS). A reported association of IHPS and eosinophilic gastroenteritis [1] raises interesting questions about the possible etiologic relationship between the two entities. It is plausible that the observed sonographic pyloric muscular wall thickness in IHPS may in part be dependent on the degree and duration of an allergic gastroenteropathy. A recent report suggests that endoscopy may be a more reliable diagnostic method than sonography in the patient with evolving IHPS [2]. Our recent experience with a patient with evolving IHPS supports the findings described in these prior reports.

Eosinophilia↗
PubMed1995

Preliminary investigation of ultrasound scattering analysis to identify women at risk for later invasive cancer. II: Extraction of dominant scattering angle-dependent trends from excised breast tissue.

Normalized estimates of the scattering angle-dependent differential scattering cross-section (DSC) at 1.0 MHz were measured from 278 samples of excised breast tissue taken from 66 women. A comparison of results for samples that contained tissue structures previously associated with an increased probability of developing breast cancer to those that did not contain high-risk structures showed that the average magnitude of DSC estimates was insufficient to identify samples with high-risk lesions. Principal component factor analysis (PCFA) was applied to extract scattering angle-dependent trends common to the entire data base. The normalized estimates of the measured DSCs (NDSC) from tissue samples are compared to estimates previously obtained from isolated breast tissue lobules as well as with results from the PCFA. Results are presented that indicate that the dominant angle-dependent trends in the NDSC results are independent of the age of the patient and are similar to trends extracted from isolated breast tissue lobules. The breast tissue structure common to all of these specimens is the terminal duct.

Adult↗
PubMed1995

Preliminary investigation of ultrasound scattering analysis to identify women at risk for later invasive cancer. I: Motivation and experimental technique for characterization of isolated breast tissue lobules.

A new experimental technique is described that allows the characterization of the angle-dependent ultrasonic scattering properties of isolated breast tissue lobules. A review of breast tissue micro-architecture is presented as background material. Measured estimates of the scatter angle-dependent differential scatter cross-sections (DSC) from 31 excised lobules (14 cancer in situ, 17 noncancer) were examined, and dominant trends described by statistical factors. Three factors were extracted, using principal component factor analysis, which collectively accounted for over 70% of the scatter angle-dependent variation exhibited by the measured data.

Breast Neoplasms↗
PubMed1995

The influence of volumetric tumor doubling time, DNA ploidy, and histologic grade on the survival of patients with intracranial astrocytomas.

PURPOSE: To improve the prediction of individual survival in patients with intracranial astrocytomas through the analysis of volumetric tumor doubling time (VDt) and DNA ploidy. METHODS: A pilot study was retrospectively conducted on a group of 25 patients with intracranial astrocytomas in whom recurrent and/or progressive disease was observed on serial contrast-enhanced CT or MR examinations. VDt was computed using two or more data points from a semilogarithmic plot of tumor volume versus time. Size-adjusted survival was calculated using a method based on VDt and initial tumor volume to decrease the lead time bias attributable to differing tumor sizes at presentation. RESULTS: Slower VDt was associated with significantly longer survival and size-adjusted survival as determined by a univariate Cox proportional hazard analysis. Aneuploidy was a significant indicator of poor survival. Aneuploid and multiclonal astrocytomas had poor size-adjusted survivals compared with diploid astrocytomas. Grade IV astrocytomas had significantly poorer survival and size-adjusted survival compared with lower grades (I to III), which individually were not significantly correlated. However, grade IV histology was not a significant independent predictor of size-adjusted survival in a multivariate Cox model, whereas VDt and DNA ploidy remained significant. VDt also had a significant direct linear correlation to survival and size-adjusted survival. CONCLUSIONS: VDt and DNA ploidy were more sensitive than histologic grading as indicators of individual survival. Initial tumor size needs to be considered when staging and assessing survival in patients with intracranial astrocytomas.

Adolescent↗
PubMed1990

Preliminary results for shear wave speed of sound and attenuation coefficients from excised specimens of human breast tissue.

A pilot study involving 53 specimens of excised human female breast tissue was performed to provide preliminary estimates of the acoustic shear wave speed of sound and linear attenuation coefficient associated with high risk for development of invasive breast cancer. The measured shear wave properties were studied as a function of: 1. whether the tissue was presented as a 2.0 to 4.0 gram mass biopsy sample or a 2.0 to 4.0 gram mass subsample taken from a larger mastectomy source; 2. the time post-excision prior to shear wave characterization; 3. the risk factor associated with the number and types of lesions found in the specimen; and 4. the percent by volume of fat or collagen present in the sample. The shear speed of sound was found to range between 20 and 900 m/s with a tendency for lower speeds as a function of time post excision. The results for shear attenuation coefficients ranged from 300 to 9000 cm-1 and did not show a marked time dependence. Average results from mastectomy specimens differed from those for biopsies, but the difference may have been due to variations in tissue composition and time post excision before shear wave characterization.

Adipose Tissue↗