Packed red blood cell transfusion (PRBC) attenuates intestinal blood flow responses to feedings in pre-term neonates with normalization at 24 hours

Objective: To determine whether packed red blood cell (PRBC) transfusion affects post-prandial superior mesenteric artery blood flow velocities (SMA BFVs) in very-low birth weight (VLBW) neonates and if so, at what time point after transfusion restoration of previous SMA BFV patterns occurs.

Design/Methods: VLBW pre-term neonates, older than 14 days and tolerating bolus enteral feedings administered every 3?h were enrolled in this prospective observational study. Pulsed Doppler ultrasound was used to measure pre- and post-prandial (at 45?min) time-averaged mean, peak and end diastolic velocities (TAMV, PSV, EDV) immediately before and after 15?ml/kg of PRBC transfusion was given over 3?h; patent ductus arteriosus (PDA) status was also evaluated. Subsequent pre- and post-prandial SMA BFVs were recorded 24 and 48?h after the transfusion.

Results: Pre- and post-prandial measurements were obtained for 21 out of 25 enrolled infants. Post-prandial SMA BFVs were attenuated during the feedings immediately after transfusion; at 24 and 48?h after transfusion, changes in post-prandial SMA BFVs were similar to those measured prior to transfusion; the presence of the PDA did not affect results.

Conclusions: PRBC transfusion blunted SMA BFV responses to feedings immediately after the transfusion with normalization observed 24?h post-transfusion.     

CD44 ligation induces apoptosis via caspase- and serine protease-dependent pathways in acute promyelocytic leukemia cells.

We have recently reported that ligation of the CD44 cell surface antigen with A3D8 monoclonal antibody (mAb) triggers incomplete differentiation and apoptosis of the acute promyelocytic leukemia (APL)-derived NB4 cells. The present study characterizes the mechanisms underlying the apoptotic effect of A3D8 in NB4 cells. We show that A3D8 induces activation of both initiator caspase-8 and -9 and effector caspase-3 and -7 but only inhibition of caspase-3/7 and caspase-8 reduces A3D8-induced apoptosis. Moreover, A3D8 induces mitochondrial alterations (decrease in mitochondrial membrane potential DeltaPsi m and cytochrome c release), which are reduced by caspase-8 inhibitor, suggesting that caspase-8 is primarily involved in A3D8-induced apoptosis of NB4 cells. However, the apoptotic process is independent of TNF-family death receptor signalling. Interestingly, the general serine protease inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF) decreases A3D8-induced apoptosis and when combined with general caspase inhibitor displays an additive effect resulting in complete prevention of apoptosis. These results suggest that both caspase-dependent and serine protease-dependent pathways contribute to A3D8-induced apoptosis. Finally, A3D8 induces apoptosis in all-trans-retinoic acid-resistant NB4-derived cells and in APL primary blasts, characterizing the A3D8 anti-CD44 mAb as a novel class of apoptosis-inducing agent in APL.     

Complement component C5a predicts restenosis after superficial femoral artery balloon angioplasty.

PURPOSE: To investigate whether balloon angioplasty of the superficial femoral artery (SFA) increases serum levels of C5a and whether C5a predicts risk of restenosis. METHODS: C5a antigen was measured at baseline and 8 hours after intervention in 131 consecutive patients (76 women; median age 72 years) with intermittent claudication who underwent successful primary SFA balloon angioplasty. Patients were followed for a median 10 months [interquartile range (IQR) 6 to 14] for the occurrence of >50% restenosis by duplex ultrasound. RESULTS: Median C5a levels increased significantly from 39.7 ng/mL (IQR 27.8 to 55.0) at baseline to 53.8 ng/mL (IQR 35.6 to 85.1, p<0.001) 8 hours post intervention. During the follow-up period, 70 (53%) patients developed restenosis. Increasing levels of C5a (quartiles) at baseline were significantly associated with an increased risk for restenosis (p=0.0092). Adjusted hazard ratios (95% confidence intervals) for restenosis with increasing quartiles of baseline serum C5a levels were 1.24 (0.60 to 2.58), 1.93 (0.95 to 3.93), and 2.08 (1.02 to 4.21), respectively, compared to the lowest quartile. This effect was independent of nonspecific inflammation as reflected by plasma levels of C-reactive protein. CONCLUSION: Inflammatory mechanisms play a major role in the development of restenosis after angioplasty. The complement component C5a exerts strong chemotactic and proinflammatory effects. Enhanced complement activation prior to PTA, as measured by higher levels of C5a, was significantly associated with restenosis after SFA balloon angioplasty. Pathways of complement inhibition thus may be worth investigating with respect to improving patency rates.     

Health Information System Implementation: A Qualitative Meta-analysis

Healthcare information systems (HISs) are often implemented to enhance the quality of care and the degree to which it is patient-centered, as well as to improve the efficiency and safety of services. However, the outcomes of HIS implementations have not met expectations. We set out to organize the knowledge gained in qualitative studies performed in association with HIS implementations and to use this knowledge to outline an updated structure for implementation planning. A multi-disciplinary team performed the analyses in order to cover as many aspects of the primary studies as possible. We found that merely implementing an HIS will not automatically increase organizational efficiency. Strategic, tactical, and operational actions have to be taken into consideration, including management involvement, integration in healthcare workflow, establishing compatibility between software and hardware and, most importantly, user involvement, education and training. The results should be interpreted as a high-order scheme, and not a predictive theory.     

Influence of Electromagnetic Fields on Function of Automated External Defibrillators

Objectives: In this study, the authors tested whether electromagnetic interference (EMI) is able to impair correct electrocardiogram analysis and produce false‐positive shock advice from automated external defibrillators (AEDs) when the true rhythm is sinus. Methods: Nineteen healthy subjects were used to test five AEDs available on the Austrian market in a prospective, open, and sequence‐randomized study. The primary outcome variable was the absolute number of shocks advised in the presence of EMI. The secondary outcome was the number of impaired analyses caused by incorrectly detected patient movements or electrode failure. Results: Of 760 tests run, 18 (2.37%) cases of false‐positive results occurred, and two of five AEDs recommended shocks in the presence of sinus rhythm. Of 760 tests run, no electrode failures occurred. There were 27 occurrences (3.55%) of motion detected by an AED in the presence of strong electromagnetic fields. Conclusions: AED models differ in their response to EMI; it may be useful to consider specific safety requirements for areas with such fields present. Working personnel and emergency medical services staff should be informed about potential risks and the possible need for patient evacuation before AEDs are attached and shock recommendations are followed.     

Ainhum (dactylolysis spontanea): A Radiological survey of 6000 patients

Dactylolysis spontanea is an idiopathic condition affecting the fifth toe, and sometimes other toes, that is frequently bilateral, with lesions in different stages. Between 1977 and 1999, a total 6000 radiographic studies of the feet were reviewed in a mainly African American population in Chicago, Illinois. After an initial screening based on the Cole criteria, 581 patients were selected and re-examined, and amplification techniques were performed. After reviewing the complementary exams, 102 patients were diagnosed with dactylolysis spontanea or ainhum. Soft-tissue constriction was the most frequently presented radiological sign on the initial screening. Kurtosis at the digit plantar fold and marked rotation of the fifth toe were normal findings in asymptomatic patients. Demographics, comorbidities, and radiological findings were analyzed in the selected population. Associated diseases occurring in these patients appeared to have no specific etiologic correlation with ainhum. African Americans and the dark-skinned population are affected exclusively by this condition, presumably due to the fibrogenic tendency of these individuals. Early diagnosis and accurate staging of ainhum are facilitated by radiological examination of the feet. The findings suggest that this condition is underdiagnosed and overlooked because its low prevalence and variable clinical presentations that might mimic more common etiologies, including localized trauma.     

Impaired in-vitro proliferation of hemopoietic precursors in HIV-1-infected subjects

Patients with acquired immunodeficiency syndrome (AIDS) and persistent lymphadenopathy syndrome (LAS) display significant hematological abnormalities of one or more cell lineages. In order to understand the pathophysiologic mechanisms leading to these abnormalities we studied the proliferation capacity of pluripotent and committed hemopoietic precursors using in-vitro colony assays. Anemia, leukopenia and thrombopenia were relatively frequent findings in HIV-infected subjects irrespectively of the patients' clinical status. The colony growth capacity of AIDS patients' GM-CFU and BFU-E was significantly decreased whereas no GEMM-CFU colonies could be obtained. There was no correlation between the number of BFU-E and GM-CFU colony number and the hemoglobin or the absolute number of polynuclear cells, respectively. The plating efficiency of both committed and pluripotent hematopoietic precursors from HIV infected patients could not be enhanced when additional exogenous recombinant GM-CSF, human interleukin 3 or erythropoietin were added in contrast to normal patients' cells. In addition, the impaired colony growth of these precursors could not be restored after adherent or T-cell depletion or the addition of normal allogenic irradiated adherent or/and T cells. Since this colony growth abnormality was also detected in HIV seropositive asymptomatic subjects our findings strongly suggest that the in-vitro growth of hematopoietic precursors is affected early after HIV-1 infection.     

Golgi apparatus in chick skeletal muscle: changes in its distribution during end plate development and after denervation.

In the course of studies about the cellular and molecular mechanisms of motor end plate formation, the distribution of the Golgi apparatus (GA) has been investigated by immunofluorescence methods in chick skeletal muscle in primary culture and in innervated muscles of 15-day-old chicks. By using a monoclonal antibody directed against the GA, we confirmed the known distribution of the GA in myogenic cells: a juxtanuclear polarized organization in myoblasts and a perinuclear nonpolarized distribution in myotubes. In contrast, the innervated anterior latissimus dorsi muscle of "young adult" chicks displayed a focal distribution of GA that appeared restricted to areas located underneath the motor end plates identified by alpha-bungarotoxin fluorescent labeling of the acetylcholine receptor. Five days after denervation of anterior latissimus dorsi muscle, a striking reorganization and expansion of the GA was observed. The GA now showed a perinuclear distribution in close association with every nucleus of the muscle fibers as observed in myotubes. The focal distribution of the GA in innervated muscle fibers and its remodeling upon denervation are interpreted in terms of a model of local synthesis, processing, and routing of acetylcholine receptor to the end plate and of regulation of these processes by functional motor innervation.