Intercomparison of bidirectional reflectance distribution function measurements at in- and out-of-plane geometries.

In recent years, there has been a growing interest in the measurements of the bidirectional reflectance distribution function (BRDF) in industry and research and development. However, there is currently no dedicated key comparison to demonstrate the scale conformity. To date, scale conformity has been proved only for classical in-plane geometries, in comparisons between different national metrology institutes (NMIs) and designated institutes (DIs). This study aims at expanding that with nonclassical geometries, including, for the first time, to the best of our knowledge, two out-of-plane geometries. A total of four NMIs and two DIs participated in a scale comparison of the BRDF measurements of three achromatic samples at 550 nm in five measurement geometries. The realization of the scale of BRDF is a well-understood procedure, as explained in this paper, but the comparison of the measured values presents slight inconsistencies in some geometries, most likely due to the underestimation of measurement uncertainties. This underestimation was revealed and indirectly quantified using the Mandel-Paule method, which provides the interlaboratory uncertainty. The results from the presented comparison allow the present state of the BRDF scale realization to be evaluated, not only for classical in-plane geometries, but also for out-of-plane geometries.

Demographic and Lifestyle Factors that affect HbA1c awareness amongst type II diabetic patients in Trinidad

• Trinidad and Tobago is amongst the countries with the greatest burden of type II diabetes in the western hemisphere • Educating type II diabetic patients in controlling their glycosylated hemoglobin (HbA1c) are recommended as measures to reduce morbidity and mortality associated with type II diabetic complications • Measurement of HbA1c in type II diabetic patients represents their glycemic history for the former 8 ­ 12 weeks and should be tested every 3 months to monitor patients' metabolic control • This study is aimed at measuring HbA1c awareness amongst T2D population in Trinidad and making recommendations based on results

Multilateral spectral radiance factor scale comparison.

The field of spectral radiance factor (SRF) measurements has seen growing interest in recent years. Scale conformity has so far only been established between the national metrology institutes (NMIs) of Germany and the USA. This study aims at a bigger, multilateral scale comparison. For this purpose, a total of six NMIs participated in a scale comparison of goniospectrophotometers based on neutral and colored diffusely reflecting ceramics samples. In addition, two universities, providing a home-built gonioreflectometer and two widely used commercially available color measurement instruments, respectively, were involved. The wavelength range of the scale comparison covers the visible wavelength range from 380 nm to 780 nm. Results indicate systematic issues and that the uncertainty evaluation of the NMIs requires further work; although for the greatest part of the covered spectral range the agreement is good.

Development of a biomimetic microfluidic oxygen transfer device.

Blood oxygenators provide crucial life support for patients suffering from respiratory failure, but their use is severely limited by the complex nature of the blood circuit and by complications including bleeding and clotting. We have fabricated and tested a multilayer microfluidic blood oxygenation prototype designed to have a lower blood prime volume and improved blood circulation relative to current hollow fiber cartridge oxygenators. Here we address processes for scaling the device toward clinically relevant oxygen transfer rates while maintaining a low prime volume of blood in the device, which is required for clinical applications in cardiopulmonary support and ultimately for chronic use. Approaches for scaling the device toward clinically relevant gas transfer rates, both by expanding the active surface area of the network of blood microchannels in a planar layer and by increasing the number of microfluidic layers stacked together in a three-dimensional device are addressed. In addition to reducing prime volume and enhancing gas transfer efficiency, the geometric properties of the microchannel networks are designed to increase device safety by providing a biomimetic and physiologically realistic flow path for the blood. Safety and hemocompatibility are also influenced by blood-surface interactions within the device. In order to further enhance device safety and hemocompatibility, we have demonstrated successful coating of the blood flow pathways with human endothelial cells, in order to confer the ability of the endothelium to inhibit coagulation and thrombus formation. Blood testing results provide confirmation of fibrin clot formation in non-endothelialized devices, while negligible clot formation was documented in cell-coated devices. Gas transfer testing demonstrates that the endothelial lining does not reduce the transfer efficiency relative to acellular devices. This process of scaling the microfluidic architecture and utilizing autologous cells to line the channels and mitigate coagulation represents a promising avenue for therapy for patients suffering from a range of acute and chronic lung diseases.

Apheresis days required for harvesting CD34+ cells predicts hematopoietic recovery and survival following autologous transplantation.

We sought to determine whether patients requiring more aphereses to obtain adequate numbers of CD34+ cells had delayed hematopoietic recovery following autologous transplantation. We identified 496 consecutive individuals with lymphoma who underwent hematopoietic stem cell mobilization using etoposide and G-CSF and first autologous transplantation. In multivariate analysis, increased apheresis days as a continuous and as a categorical variable at ≥5/<5 days significantly predicted neutrophil recovery. Apheresis days fell just short of significance (P=0.06) as a predictor of platelet recovery in multivariate analysis. Increased apheresis days (as both continuous and categorical variables) were also predictive of treatment-related myelodysplastic syndrome/AML. Patients who underwent ≥5 days of pheresis had significantly worse survival (P=0.001) than patients with less pheresis days owing to significantly higher relapse mortality (P=0.001).

Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte function.

BACKGROUND: Accelerating the clearance of therapeutic monoclonal antibodies (mAbs) from the body may be useful to address uncommon but serious complications from treatment, such as progressive multifocal leukoencephalopathy (PML). Treatment of PML requires immune reconstitution. Plasma exchange (PLEX) may accelerate mAb clearance, restoring the function of inhibited proteins and increasing the number or function of leukocytes entering the CNS. We evaluated the efficacy of PLEX in accelerating natalizumab (a therapy for multiple sclerosis [MS] and Crohn disease) clearance and alpha4-integrin desaturation. Restoration of leukocyte transmigratory capacity was evaluated using an in vitro blood-brain barrier (ivBBB). METHODS: Twelve patients with MS receiving natalizumab underwent three 1.5-volume PLEX sessions over 5 or 8 days. Natalizumab concentrations and alpha4-integrin saturation were assessed daily throughout PLEX and three times over the subsequent 2 weeks, comparing results with the same patients the previous month. Peripheral blood mononuclear cell (PBMC) migration (induced by the chemokine CCL2) across an ivBBB was assessed in a subset of six patients with and without PLEX. RESULTS: Serum natalizumab concentrations were reduced by a mean of 92% from baseline to 1 week after three PLEX sessions (p < 0.001). Although average alpha4-integrin saturation was not reduced after PLEX, it was reduced to less than 50% when natalizumab concentrations were below 1 mug/mL. PBMC transmigratory capacity increased 2.2-fold after PLEX (p < 0.006). CONCLUSIONS: Plasma exchange (PLEX) accelerated clearance of natalizumab, and at natalizumab concentrations below 1 mug/mL, desaturation of alpha4-integrin was observed. Also, CCL2-induced leukocyte transmigration across an in vitro blood-brain barrier was increased after PLEX. Therefore, PLEX may be effective in restoring immune effector function in natalizumab-treated patients.

A randomized trial of etoposide and G-CSF with or without rituximab for PBSC mobilization in B-cell non-Hodgkin's lymphoma.

Some reports have suggested that rituximab administration before PBSC mobilization may adversely affect PBSC yield. We conducted a prospective randomized trial of PBSC mobilization using etoposide and G-CSF with or without rituximab to determine whether its addition would adversely affect CD34+ cell yield in patients with non-Hodgkin's lymphoma. Twenty seven patients were mobilized with etoposide and G-CSF and 28 with etoposide, G-CSF and rituximab. There were no adverse consequences of rituximab on CD34+ cell yield, or hematopoietic recovery or immunoglobulin levels after transplantation.

Patients mobilizing large numbers of CD34+ cells ('super mobilizers') have improved survival in autologous stem cell transplantation for lymphoid malignancies.

The cellular composition of an autologous graft may influence autologous stem cell transplantation (ASCT) outcome. Etoposide (VP) plus filgrastim (G) frequently mobilizes high numbers of CD34+ cells for autologous transplantation. We investigated whether patients collecting high numbers of CD34+ cells ('super mobilizers') have a better outcome than other patients. We reviewed 350 consecutive adult patients with NHL or Hodgkin's lymphoma receiving an ASCT from January 1994 to December 2005, mobilized with VP+G. Super mobilizers were defined as collecting a minimum of 8 x 10(6) CD34+ cells/kg. Two hundred and three patients were super mobilizers, while 147 collected between 2.0 and 7.95 CD34+ cells/kg. Super mobilizers were younger and more likely to have received two or fewer prior chemotherapy regimens (80 versus 63%, P<0.001). Median CD34+ cell dose for the super mobilizing group was 13.7 x 10(6) versus 4.4 x 10(6)/kg in the standard collecting group. The super mobilizer group had a superior overall survival (P=0.006). In multivariable analysis, favorable disease status and younger age at transplant, and super mobilization were associated with improved survival. We conclude that patients had an improved ASCT outcome if large numbers of CD34+ cells were mobilized and infused. The explanation for this observation is unknown.

Thrombotic microangiopathy and cytomegalovirus in liver transplant recipients: a case-based review.

BACKGROUND: Thrombotic microangiopathy (TMA) is a rare but potentially lethal complication encountered in solid organ and bone marrow transplant recipients, requiring rapid recognition, diagnosis, and initiation of therapy. Several potential causes have been identified in this setting, including viral infections and medications. METHODS: We report a case of TMA in a liver transplant recipient with active cytomegalovirus (CMV) gastritis. A 41-year-old female presented 3 months after liver transplantation with a 5-week history of nausea, vomiting, anorexia, and diarrhea. CMV serology was donor seropositive and recipient seronegative (D+/R-). The immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil, and prednisone. Evaluation revealed CMV viremia with a high viral load and intravenous ganciclovir was started. A decline in hemoglobin and platelets with an increase in lactate dehydrogenase (LDH) warranted hematologic evaluation, which revealed findings consistent with microangiopathic hemolytic anemia. Ganciclovir and tacrolimus were discontinued. Intravenous immunoglobulin was administered and daily plasmapheresis was initiated. As the patient's blood counts and LDH started to improve, ganciclovir was cautiously reinstituted. The patient's gastrointestinal symptoms gradually resolved and her blood counts continued to improve with prolonged plasmapheresis (a total of 23 plasmapheresis sessions). Tacrolimus and possibly CMV infection were suspected to be the cause for her TMA, and cyclosporine was substituted. CONCLUSIONS: TMA is an important entity in the differential diagnosis of acute hemolytic anemia in liver transplant recipients. Many cases seem to be medication-induced. However, in treatment-resistant or relapsing cases, a possibility of concomitant CMV infection should be considered.

Thrombin-enhanced matrix metalloproteinase-1 expression: a mechanism linking placental abruption with premature rupture of the membranes.

OBJECTIVE: Given the strong clinical association between the decidual hemorrhage of placental abruption and subsequent preterm premature rupture of the membranes, we assessed the effects of thrombin on the expression of the potent interstitial collagenase, matrix metalloproteinase-1 (MMP-1), in cultured endometrial stromal and decidual cells. STUDY DESIGN: Stromal cells derived from predecidualized cycling endometrium and decidual cells from term decidua were cultured in a defined medium containing estradiol, to mimic the hormonal milieu of the non-pregnant proliferative phase, or estradiol plus medroxyprogesterone acetate (MPA), to mimic the hormonal milieu of pregnancy, in the presence and absence of thrombin. Culture media were examined for MMP-1 protein levels and cell lysates were examined for steady-state MMP-1 mRNA levels. RESULTS: MPA strongly inhibited MMP-1 levels in endometrial stromal and term decidual cells. However, thrombin overcame this suppression, producing MMP-1 levels that were several-fold higher than control levels. CONCLUSION: Extrapolation of thrombin-enhanced MMP-1 expression in cultured endometrial stromal and decidual cells to the in vivo pregnant state provides an explanation for the strong association between placental abruption and preterm membrane rupture.

Differential effects of thrombin and hypoxia on endometrial stromal and glandular epithelial cell vascular endothelial growth factor expression.

Ovarian steroids and/or premenstrual endometrial hypoxia are thought to restore the endometrial vasculature shed during menstruation by elevating endometrial vascular endothelial growth factor (VEGF) levels. During the luteal phase, VEGF levels peak, progesterone induces estradiol (E(2))-primed human endometrial stromal cells (HESCs) to decidualize and express tissue factor (TF), and endometrial vascular permeability is enhanced. The latter would present circulating clotting factors to decidual cell-expressed TF to form local thrombin. HESCs were incubated in serum-supplemented medium containing vehicle (control) or 10(-8) M E(2) or 10(-7) M medroxyprogesterone acetate (MPA) or E(2) + MPA for 7 d to induce decidualization, while monolayers of human endometrial glandular epithelial cells (HEGECs) formed during 4-d incubation of glands. The medium was exchanged for a defined medium containing corresponding vehicle or steroids +/- thrombin under normoxia or hypoxia (0-1% O(2)). Hypoxia enhanced secreted immunoreactive VEGF levels by severalfold in HESCs and HEGECs, but the steroids did not affect VEGF output in either cell type under normoxia or hypoxia. In E(2) + MPA-decidualized HESCs, VEGF levels were elevated by 0.1 U/ml of thrombin, and 0.5-2.5 U/ml of thrombin elicited maximum effects. The addition of 0.5 U/ml of thrombin evoked a time-dependent enhancement of VEGF levels and about an 8-fold increase at 48 h (P < 0.02; n = 6). Northern blotting indicated that E(2) + MPA-decidualized HESCs expressed VEGF(121), VEGF(165), and VEGF(189) mRNA, which were enhanced severalfold during 5- to 20-h incubation with thrombin. Moreover, TRAP, a synthetic peptide activator of the constitutively expressed protease activated receptor-1 thrombin receptor in decidualized HESCs, also elevated secreted VEGF levels. By contrast, HEGECs were unresponsive to thrombin added alone or with ovarian steroids. These results suggest that thrombin formed by progestin-augmented TF levels acts as an autocrine enhancer of VEGF expression in decidualized HESCs. Because angiogenesis occurs in a matrix of decidualized HESCs, these in vitro results provide a novel mechanism to account for both the peak in VEGF and angiogenesis in luteal phase human endometrium.

Apheresis technologies and clinical applications: the 2000 International Apheresis Registry.

The developments in apheresis technologies and techniques and their clinical applications worldwide are technologically, sociologically, and economically driven. In the past, apheresis survey statistics have highlighted both the differences by geographical region in clinical practices and in the types of technologies utilized. While a national view of apheresis is critically important, an international view of apheresis may be more representative overall of this therapeutic modality than national results that are highly dependent on the local economics and the available technologies. These regional differences have provided a basis for the scientific and clinical assessments of these apheresis technologies and their clinical outcomes and have impacted the marketing and business developments of new technologies worldwide. The results of the International Apheresis Registry for 2000 reporting on 39 centers on 4 continents are presented. This survey collected data on 1,080 patients for a total of 15,257 treatments. Information gathered included patient demographics, medical history, treatment diagnoses, treatment specifics (type, methodology, access type, anticoagulants, drugs, equipment usage), side effects, clinical response, and payment provider. As in the prior International Apheresis Registry for 1983, the survey results highlighted the regional differences in apheresis usage and treatment specifics, indicating that an international overview of apheresis may be more representative of the impact of this therapeutic modality.

Photopheresis in the treatment of refractory bronchiolitis obliterans complicating lung transplantation.

Photopheresis has been successfully used to treat heart allograft rejection and has had some initial success in the treatment of bronchiolitis obliterans (BO) following lung transplantation. This report describes five patients treated with photopheresis after the failure of augmented immunosuppression for BO. Four patients had a temporary stabilization of their airflow obstruction, and minimal side effects of the procedure were noted, although there were consequences from additional augmented immunosuppression (principally sepsis). Photopheresis may provide a safe modality for the treatment of BO that is unresponsive to standard and augmented immunosuppression.

Overview of therapeutic apheresis in the U.S.A.

This article provides an overview of therapeutic plasma exchange in the United States. The original continuous flow blood cell separator was developed in the U.S.A. and remains the most popular type of equipment used. Treatments are expensive and limited by insurance reimbursement. Covered diseases are already established, with most of the treatments falling into those for hematologic and neurologic diseases. The majority of therapeutic plasma exchange is performed for a limited number of diagnoses. An estimated 110,000 treatments were provided in 1997, the majority in hospital-based units. It is unclear whether these numbers will increase or decline with the increasing limitations in reimbursement by insurance companies.

Variables associated with the platelet count 6 weeks after autologous peripheral blood progenitor cell transplantation.

While abundant data exist documenting variables associated with early platelet engraftment after autologous PBPC transplantation, data concerning later sustained platelet engraftment is sparse. We retrospectively examined a series of 80 patients undergoing autologous PBPC transplantation with respect to their platelet count 6 weeks after transplant. Underlying diagnoses included breast cancer (n = 33), non-Hodgkin's lymphoma (n = 32), Hodgkin's disease (n = 9), and other hematologic malignancies (n = 6). Patients received G-CSF for PBPC mobilization and collected a target threshold number of 2.0 x 10(6) CD34+ cells per kilogram. A univariate analysis revealed that a diagnosis of breast cancer, fewer courses of prior chemotherapy, younger age and complete remission were associated with a higher 6-week platelet count. Additionally, the ability to collect the threshold number of CD34+ with fewer sessions of leukapheresis was also associated with a higher 6-week platelet count. The platelet count and the white blood cell count at the initiation of PBPC collection was also associated with a higher 6-week platelet count. A multivariate analysis revealed a higher platelet count on the first day of pheresis, fewer phereses required to collect 2 x 10(6) CD34+ cells per kilogram, and a diagnosis of breast cancer were all associated with a higher 6-week post-transplant platelet count. Seven patients failed to reach a 6-week platelet count of 30 x 10(9)/l and an additional five patients had a platelet count of 30-50 x 10(9)/l. We conclude that underlying clinical characteristics, as well as hematologic variables at the time of PBPC collection, influence later, sustained platelet engraftment. A percentage of patients have poor sustained platelet engraftment and may be candidates for new cytokines that specifically target megakaryocyte growth and development.

Functional evidence linking potassium channels and afferent nerve-mediated mucosal protection in rat stomach.

Adenosine triphosphate-dependent potassium (K+ATP) channels in several types of vascular smooth muscles mediate the vasodilation induced by calcitonin gene-related peptide (CGRP). Upon stimulation, primary afferent nerve terminals in the gastric mucosa release CGRP which mediates a protective hyperemia. We tested the hypothesis that a potassium channel blocker aggravates gastric mucosal injury by impairing afferent nerve-mediated hyperemia in the gastric mucosa. Rats were treated with K+ATP channel blocker, glybenclamide (20 mg/kg intravenously). Intragastric added ethanol (0.15 N HCl, 15% ethanol) and intragastric capsaicin (160 microM) were also administered. Glybenclamide aggravated the acidified ethanol-induced mucosal injury, and attenuated the mucosal hyperemia (hydrogen gas clearance) induced by intragastric acidified ethanol and intragastric capsaicin. These findings suggest for the first time that K+ATP channels modulate primary afferent nerve-mediated mucosal defense mechanisms in the gastric mucosa.

Selective ablation of astrocytes by intracerebral injections of alpha-aminoadipate.

The efficacy and the specificity of the putative astrotoxin, alpha-aminoadipate, were examined in this study. The integrity of astrocytes was evaluated at several time points following a single injection of alpha-aminoadipate into amygdala of adult rats using immunohistochemistry. The density and the morphological appearance of neurons and the response of microglia were also examined. The injection of alpha-aminoadipate disrupted the astrocytic network in that region. There was a profound loss of glial fibrillary acidic protein-positive and S100 beta-positive astrocytes, normally present in the region, while vimentin immunohistochemistry revealed the presence of deformed cell processes, presumably astrocytic. The presence of reactive microglia at the injection site was suggestive of an active degenerative process, while the normal neuronal density and appearance, as compared to controls, suggested that the damage was confined to astrocytes. The confirmed effectiveness and cellular specificity of alpha-aminoadipate in vivo makes it a potentially important experimental tool for attempting to decipher the functional significance of astrocytes.