Hematology patterns after hemoglobin-based oxygen carrier resuscitation from severe controlled hemorrhage with prolonged delayed definitive care

BACKGROUND: The hemoglobin-based oxygen carrier (HBOC-201) resuscitation fluid improves outcome in hemorrhagic shock swine models with minimal coagulopathy. Herein, coagulation parameters were evaluated after resuscitation with HBOC-201 after severe bleeding and prolonged delay to definitive care. STUDY DESIGN AND METHODS: After 55 percent estimated blood volume-controlled hemorrhage by catheter withdrawal, swine (n=48) were resuscitated with HBOC-201 or Hextend (HEX) infused in four doses over 4 hours or not resuscitated (NON). Animals were randomly assigned in two cohorts of 4- or 24-hour simulated delay to hospital arrival (access to blood and saline infusions up to 72 hr). In vitro hematologic monitoring was assessed with complete blood count, hemostasis (thromboelastography [TEG], in vitro bleeding time [PFA]), and coagulation (prothrombin time [PT], thrombin-antithrombin, fibrinogen) indices. RESULTS: Within groups, survival was unaffected by extending delay from 4 to 24 hours. Combined survival was similar for HBOC-201 and HEX but lower for NON animals (93.5, 81.5, and 25 percent, respectively; p<0.01). Blood transfusion requirements were lower with HBOC-201 than HEX. Elevated TEG and PFA parameters in resuscitated animals reflected fluid and blood transfusion regimens. TEG reaction time and PFA were transiently higher with HBOC-201 than with HEX during the early hospital phase. PT was increased in HEX animals. CONCLUSION: In this severe model, survival was equivalent with HBOC-201 and HEX resuscitation. HBOC-201 or HEX allowed delayed hospital arrival to 24 hours without worsening coagulation parameters, but dilutional mild coagulopathy in the hospital phase persisted with HBOC-201 due to blood transfusion avoidance. Low hematocrit suggests that blood administration after HBOC-201 resuscitation could be beneficial to replete blood cellular mass.     

An international collaboration to standardize HIV-2 viral load assays: results from the 2009 ACHI(E)V(2E) quality control study

Accurate HIV-2 plasma viral load quantification is crucial for adequate HIV-2 patient management and for the proper conduct of clinical trials and international cohort collaborations. This study compared the homogeneity of HIV-2 RNA quantification when using HIV-2 assays from ACHI(E)V(2E) study sites and either in-house PCR calibration standards or common viral load standards supplied to all collaborators. Each of the 12 participating laboratories quantified blinded HIV-2 samples, using its own HIV-2 viral load assay and standard as well as centrally validated and distributed common HIV-2 group A and B standards (http://www.hiv.lanl.gov/content/sequence/HelpDocs/subtypes-more.html). Aliquots of HIV-2 group A and B strains, each at 2 theoretical concentrations (2.7 and 3.7 log(10) copies/ml), were tested. Intralaboratory, interlaboratory, and overall variances of quantification results obtained with both standards were compared using F tests. For HIV-2 group A quantifications, overall and interlaboratory and/or intralaboratory variances were significantly lower when using the common standard than when using in-house standards at the concentration levels of 2.7 log(10) copies/ml and 3.7 log(10) copies/ml, respectively. For HIV-2 group B, a high heterogeneity was observed and the variances did not differ according to the type of standard used. In this international collaboration, the use of a common standard improved the homogeneity of HIV-2 group A RNA quantification only. The diversity of HIV-2 group B, particularly in PCR primer-binding regions, may explain the heterogeneity in quantification of this strain. Development of a validated HIV-2 viral load assay that accurately quantifies distinct circulating strains is needed.     

Liver Recurrence of a Subcutaneous Temporal Hemangiopericytoma: The Index Case

Introduction  Hemangiopericytoma is an uncommon soft tissue vascular neoplasm. Intraperitoneal hemangiopericytomas such as primary or secondary liver location have been exceptionally described. Its natural history is mostly benign, but recurrences may occur and determining if these late-discovered tumors are distant metastases or synchronous slow and silent-growing locations is sometimes challenging. The histopathological diagnosis and definition of hemangiopericytoma is based on its distinction with solitary fibrous tumors. Liver resection to treat liver hemangiopericytoma seems to be supported by various published experiences. Case presentation  We herein report the first case of liver metastases from a subcutaneous temporal hemangiopericytoma. The patient was treated by a liver resection. CD34 Immunostaining was negative, but strong expression of Bcl2 and CD99 was found in the neoplastic cells. After 1 year of follow-up, the patient is alive without recurrence. Conclusion  To date, published data, including the case herein reported, support the need for a prolonged follow-up and the role of liver resection to treat liver metastases of hemangiopericytomas. Complete resection of all gross disease appears to be the most significant prognostic factor.     

Effects of Yearly Zoledronic Acid 5 mg on Bone Turnover Markers and Relation of PINP With Fracture Reduction in Postmenopausal Women With Osteoporosis

In patients with osteoporosis treated with antiresorptive agents, reduction in bone turnover explains much of the observed fracture risk reduction. Lower levels of bone turnover markers (BTMs) appear to be associated with a lower risk of fracture in bisphosphonate‐treated patients. BTMs were measured in a subset of subjects in the HORIZON Pivotal Fracture Trial. Annual infusions of zoledronic acid 5 mg significantly reduced BTMs: median decrease of 50% for β‐C‐terminal telopeptides of type 1 collagen (β‐CTX), 30% for bone alkaline phosphatase (ALP), and 56% for procollagen type 1 amino‐terminal propeptide (PINP). The mean level of BTMs decreased in treated patients but remained within the premenopausal range before the next injection. The percentage of zoledronic acid–treated patients with values below the premenopausal reference range at all time points was 1.7%, 17.8%, and 19% for bone ALP, CTX, and PINP, respectively. The third injection of zoledronic acid resulted in 60% reduction of β‐CTX within 9–11 days, followed by a gradual increase, indicating the persistence of osteoclastic bone resorption. The association between changes in BTMs and fracture incidence was assessed in 1132 patients who had PINP measurements at baseline and 1 yr. There was no association between low PINP levels at 1 yr and increased fracture incidence. In summary, (1) annual injections of zoledronic acid reduced BTMs in the premenopausal range, with a significant response persisting after the third infusion; and (2) low levels of PINP were not associated with increased fracture risk.     

Apoptosis in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy

To test the hypothesis that an apoptotic process plays a role in the pathogenesis of cerebral lesions in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), we examined samples from frontal, temporal, insular, and occipital regions, basal ganglia, and cerebellum from 4 patients with CADASIL, 2 with Binswanger disease, and 3 controls. Apoptotic cells were identified using in situ end labeling and activated caspase 3 immunostaining. Immunolabeling for Notch3, the beta-amyloid protein precursor, and phosphorylated neurofilament protein was performed on successive sections. Apoptosis of vascular cells was markedly increased in status cribrosus in CADASIL, both in basal ganglia and subcortical white matter, suggesting that concomitantly with Notch3 deposition it may play a causative role in the dilatation of Virchow-Robin spaces. Neuronal apoptosis was found in CADASIL, mostly in cortical layers 3 and 5. Its severity correlated semiquantitatively with the extent of ischemic lesions and axonal damage in the underlying white matter. It was more severe in demented patients. Only occasional apoptotic neurons were found in the Binswanger cases and none in the controls. This supports the view that neuronal apoptosis may contribute to cortical atrophy and cognitive impairment in patients with CADASIL and that it may, at least partly, result from axonal damage in the underlying white matter.     

Monitoring the dynamics of the HIV epidemic using assays for recent infection and serotyping among new HIV diagnoses: experience after 2 years in France

BACKGROUND: New tools to better monitor dynamics of human immunodeficiency virus (HIV) transmission are needed. METHODS: National surveillance of newly HIV diagnoses included the collection of dried serum spots to identify both recent infections (<6 months) and HIV serotypes. Multivariate analyses were used to identify factors associated with recent infection and infection with non-B subtypes. RESULTS: Between 2003 and March 2005, 7902 new HIV diagnoses were reported. The overall proportion of recent infections was 24.9% (95% confidence interval, 23.8%-26.0%) and was highest among men who have sex with men (MSM; 46%). Recent infection was associated with being an MSM, <30 years old, of French nationality, and living in Paris. Nearly half of newly HIV-1 diagnoses were with non-B subtypes. The highest proportion of non-B infections was reported among African heterosexual persons (81%), but important proportions were reported among French heterosexual persons (34%) and MSM (12%). Being infected by a non-B subtype was independently associated with being African, <30 years old, heterosexual, and living in Paris. The proportion of HIV-2 infection was 1.9%, and 11 cases of HIV-1 group O infection were identified, mainly among West Africans. CONCLUSIONS: There is evidence of high levels of HIV transmission among MSM in France and transmission of non-B subtypes within the indigenous French population.     

Bromocriptine-induced hyperglycemia in nonobese diabetic mice: kinetics and mechanisms of action

The effects of bromocriptine (10 mg/kg), known to inhibit prolactin secretion and lower autoimmune processes, were studied on glucose homeostasis in non-fasted non-obese diabetic mice, a spontaneous model of type 1 diabetes. Hyperglycemia was observed 120 and 240 min after i.p. but not s.c. injection. Bromocriptine administration i.p. led to rapid and marked hyperglycemia characterized by sexual dimorphism with males having higher glycemia than females. Bromocriptine induced a rapid but transient decrease in insulinemia in males only and biphasic increases in glucagon levels and a sustained stimulatory effect on circulating corticosterone in both sexes. Bromocriptine-induced hyperglycemia involved D2-dopaminergic receptors, as demonstrated by the inhibitory effect of the D2-dopamine antagonist, metoclopramide (10 mg/kg). Simultaneous injection of bromocriptine and metoclopramide also blocked the rise in blood corticosterone. In conclusion, by inducing hyperglycemia, i.p. bromocriptine administration to prediabetic autoimmune mice may counteract its beneficial anti-immunostimulatory effects.