Mobilization of early hematopoietic progenitor cells with BB-10010: a genetically engineered variant of human macrophage inflammatory protein- 1 alpha

BB-10010 is a genetically engineered variant of human macrophage inflammatory protein-1 alpha with improved solution properties. We show here that it mobilizes stem cells into the peripheral blood. We investigated the mobilizing effects of BB-10010 on the numbers of circulating 8-day spleen colony-forming units (CFU-S8), CFU-S12, and progenitors with marrow repopulating ability (MRA). A single subcutaneous dose of BB-10010 caused a twofold increase in circulating numbers of CFU-S8, CFU-S12, and MRA 30 minutes after dosing. We also investigated the effects of granulocyte colony-stimulating factor (G- CSF) and the combination of G-CSF with BB-10010 on progenitor mobilization. Two days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA progenitors by 25.7-, 19.8-, and 27.7-fold. A single administration of BB-10010 after 2 days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA even further to 38-, 33-, and 100- fold. Splenectomy resulted in increased circulating progenitor numbers but did not change the pattern of mobilization. Two days of treatment with G-CSF then increased circulating CFU-S8, CFU-S12, and MRA by 64-, 69-, and 32-fold. A single BB-10010 administration after G-CSF treatment further increased them to 85-, 117-, and 140-fold, respectively, compared with control. We conclude that BB-10010 causes a rapid increase in the number of circulating hematopoietic progenitors and further enhances the numbers induced by pretreatment with G-CSF. BB- 10010 preferentially mobilized the more primitive progenitors with marrow repopulating activity, releasing four times the number achieved with G-CSF alone. Translated into a clinical setting, this improvement in progenitor cell mobilization may enhance the efficiency of harvest and the quality of grafts for peripheral blood stem cell transplantation.     

Case finding and referral model for emergency department elders: a randomized clinical trial

STUDY OBJECTIVE: Elderly emergency department patients have complex medical needs and limited social support. A transitional model of care adapted from hospitals was tested for its effectiveness in the ED in reducing subsequent service use. METHODS: A randomized clinical trial was conducted at 2 urban, academically affiliated hospitals. Participants were 650 community-residing individuals 65 years or older who were discharged home after an ED visit. Main outcomes were service use rates, defined as repeat ED visits, hospitalizations, or nursing home admissions, and health care costs at 30 and 120 days. Intervention consisted of comprehensive geriatric assessment in the ED by an advanced practice nurse and subsequent referral to a community or social agency, primary care provider, and/or geriatric clinic for unmet health, social, and medical needs. Control group participants received usual and customary ED care. RESULTS: The intervention had no effect on overall service use rates at 30 or 120 days. However, the intervention was effective in lowering nursing home admissions at 30 days (0.7% versus 3%; odds ratio 0.21; 95% confidence interval [CI] 0.05 to 0.99) and in increasing patient satisfaction with ED discharge care (3.41 versus 3.03; mean difference 0.37; 95% CI 0.13 to 0.62). The intervention was more effective for high-risk than low-risk elders. CONCLUSION: An ED-based transitional model of care reduced subsequent nursing home admissions but did not decrease overall service use for older ED patients. Further studies are needed to determine the best models of care for this setting and for at-risk patients.     

In vivo expression of the B7 costimulatory molecule by subsets of antigen-presenting cells and the malignant cells of Hodgkin's disease

The B-lymphocyte/accessory-cell activation antigen B7 (BB1) has been shown in vitro to stimulate T-lymphocyte proliferation and cytokine production via CD28 present on the latter cells. In this study, benign lymphoid tissues, lymphomas, and extralymphoid inflammatory sites were examined immunohistochemically using anti-B7 and other relevant monoclonal antibodies. B7 was expressed by benign transformed germinal center B cells, as it was by B cells of follicular lymphomas. B7 was also expressed by a subpopulation (a mean of 31% to 65%) of macrophages and dendritic cells in a variety of lymphoid tissues. It was present in abundance on all macrophages constituting sarcoid granulomas in lymph nodes. In extralymphoid inflammation, 17% to 35% of macrophages expressed B7 only weakly. Cases of Hodgkin's disease showed expression of B7 by the majority of Reed-Sternberg cells or malignant mononuclear variants, a phenomenon that potentially contributes to the lymphocytic accumulation that is a feature of this condition. CD28+ T cells were seen in all areas where T cells were present. B7+ and CD28+ cells colocalized in, for example, lymphoid follicles, lymph node paracortex, sarcoid granulomas, and Hodgkin's disease tissue, indicating a potential for cellular interaction via these molecules at these sites.     

Clinical trials of the pneumatic antishock garment in the urban prehospital setting

As a result of experimental data and favorable clinical impressions, the pneumatic antishock garment (PASG) has gained widespread acceptance as a reasonable standard of care in emergency medical services (EMS) systems. It is currently legislated as required equipment for medical rescue vehicles in two-thirds of the United States. But despite a decade of widespread use, prospective, randomized, controlled trials that demonstrate the efficacy of the PASG have not been published. Furthermore, certain complications have been reported and concerns have been raised about the use of the PASG under certain circumstances, such as penetrating thoracic injury. In the fall of 1983, the City of Houston EMS system embarked on a long-term prospective evaluation of PASG use in hypotensive victims of injury in the urban prehospital setting. All victims of injury whose systolic blood pressure was 90 mm Hg or less when they initially presented to paramedics in the field were entered into the study. All patients received the identical treatment protocol, with the sole exception of PASG application and inflation to full pressure prior to intravenous catheterization on an alternate day basis. Prospectively collected demographic data have demonstrated that the two resulting groups of PASG and no-PASG patients are well matched in terms of age, sex, injury type, anatomic location of the injury, initial field trauma score, injury severity score and probabilities of survival, as well as the amounts of IV fluids infused in the prehospital setting and the response, scene, and transport times.(ABSTRACT TRUNCATED AT 250 WORDS)     

A study of classification criteria for a diagnosis of juvenile rheumatoid arthritis

Criteria for the classification of juvenile rheumatoid arthritis were analyzed in a detailed database of 250 children in order to assess the accuracy of diagnosis and validity of onset types and course subtypes. A number of conclusions have been derived from this study: All definitions of the 1973 criteria for classification of juvenile rheumatoid arthritis should be retained. The addition of onset types to the 1976 revision of the criteria has been validated. The course of the disease after the onset period of 6 months is as important to the outcome of a group of children as is the onset type. The current classification should be broadened to include the course subtypes.     

Chronic treatment with bovine growth hormone upregulates high-affinity hepatic somatotropic receptors in sheep

We evaluated the effect of chronic bovine growth hormone treatment on the hepatic somatotropic receptor. Growing lambs were treated with bGH at 0, 0.05, 0.15, 0.25 or 0.55 mg.kg-1.day-1 daily (N = 5/group) for 56 days. The binding of ovine GH to hepatic membranes washed with 4 mol/l MgCl2 and prepared in the presence of aprotinin was examined. The specific binding of oGH was increased (p less than 0.01) from 7.1 +/- 1.2% in saline-treated controls to 17.4 +/- 1.5% in the 0.55 mg.kg-1.day-1 group. Scatchard analysis showed curvilinear plots that best fitted a two-site model in 22/25 livers. The two sites had estimated dissociation constants (Kd) of 3 to 13 nmol/l for the low-affinity site and a Kd ranging from 0.17 to 0.31 nmol/l for the high-affinity site. Treatment with bGH had no consistent effect on the affinity of either binding site. However, bGH therapy was associated with a dose-dependent increase (p less than 0.01) in the number of high-affinity somatotropic receptors. There was no effect of bGH therapy on the concentration of low-affinity binding sites. The concentration of high-affinity receptors correlated with weight gain (r = 0.54, p less than 0.01), fat content (r = -0.54, p less than 0.01), protein content (r = 0.40, p less than 0.05), and plasma IGF-I (r = 0.57, p less than 0.005). The concentrations of low-affinity binding sites showed no such correlations.(ABSTRACT TRUNCATED AT 250 WORDS)     

PFO closure complications from the AGA registry

Objectives: To evaluate all complications that occurred during or after cardiac catheterizations for Amplatzer PFO device closure of patent foramen ovale (PFO), determine the cause of the complications and recommend techniques to minimize complications in the future. Background: Rare complications were reported to the manufacturer of the Amplatzer PFO occluder since the introduction of the device. Methods: A panel of independent physicians reviewed all complications reported to the manufacturer to determine whether the complication was related to the device or related to the cardiac catheterization procedure. Demographic data, echocardiograms, operative reports, and time to occurrence of complications were reviewed. Results: A total of 11 events were reported. Only two patients had device related complications (erosion), an incidence of 0.018%. Two patients were found to have additional atrial septal defect after PFO closure. Two patients were thought to have an inflammatory reaction without any serious sequelae. Five complications were related to the cardiac catheterization procedure (atrial appendage perforation). Conclusions: Device related complications after Amplatzer PFO occluder placement are extremely rare. Cardiac catheterization related complications appear to be the most common cause of the hemodynamic compromise. Careful manipulation of catheters and wires, recognition of the location of the catheter by fluoroscopy and echocardiography will decrease the risk of such complications. © 2008 Wiley‐Liss, Inc.     

Thoracentesis in patients with hematologic malignancy: yield and safety

BACKGROUND: Pleural effusions occur in patients with hematologic malignancies, particularly during periods of hospitalization. Thoracentesis is often performed to diagnose infection and to exclude the presence of complicated parapneumonic effusions. The efficacy and safety of thoracentesis in this setting has not been well-studied. DESIGN: Retrospective chart review of hospitalized patients with hematologic malignancies undergoing thoracentesis. The aim of this study was to assess the role of thoracentesis in establishing a diagnosis of infection in this population and to determine the risk of complications. RESULTS: A total of 100 thoracentesis findings were analyzed in patients with lymphoma (52 patients) and leukemia (27 patients), and in patients who had undergone bone marrow or stem cell transplantation (21 patients). The indication for performing thoracentesis was to exclude infection in 69% of cases. Fever was present in 59% of the patients, and a concomitant lung parenchymal abnormality was present in 69% of cases. Effusions were moderate to large in size (87% of cases), and were both bilateral (62%) and unilateral (38%). Exudates were documented in 83%of the cases. A specific diagnosis was found in 21 patients and was more frequently established in those with lymphoma (31%) compared to the other groups of patients. Diagnoses found included malignancy in 14 cases, chylous effusions in 6 cases, and infection in 1 case. The one patient in whom empyema was found required drainage. The criteria for a parapneumonic effusion were not found in any other patients. The complication rate of 9% (pneumothorax, seven patients; hemothorax, two patients) was comparable to that in other populations of patients. CONCLUSIONS: Despite a high propensity for developing pulmonary infections, hospitalized patients with hematologic malignancies rarely developed complex parapneumonic effusions. The etiology of many of the effusions that occurred in this setting was unclear.     

Pulmonary embolism in post-mortem material with clinical correlations in 425 cases

425 patients with pulmonary emboli at post mortem were studied retrospectively with the main focus on the clinical diagnosis. The diagnosis of pulmonary embolus was made or suspected while the patient was still alive in 59 patients (14%) and was first written in the post mortem request form in 130 patients (30%). In 236 patients (56%) the diagnosis was made only at post mortem. Even in fatal emboli the diagnosis was missed in 43% of cases. A multiplicity of non specific symptoms and signs was observed with a minority of patients showing signs and symptoms considered as typical. Of 231 thrombophlebitis processes found in locations which could give rise to clinical symptoms in the lower extremities the diagnosis was noted only in 25 cases. Chest x-ray and ECG were negative in two thirds of the cases. The high rate of misdiagnosis derived from two reasons: (a) subjective factors: lack of awareness; (b) objective difficulties: lack of specificity of clinical symptoms and signs as well as of results of the routine tests (chest x-ray and ECG). Since sophisticated confirmative tests for pulmonary emboli will be performed only on the basis of clinical suspicion, clinical awareness based on the observations detailed in this survey is still the cornerstone of diagnosis.