Increased thromboxane biosynthesis in normal pregnancy is mainly derived from platelets

Thromboxane biosynthesis was determined in normal pregnant subjects by measurement of its major urinary and plasma metabolites, 2,3-dinor-thromboxane B2 and 11-dehydro-thromboxane B2. Urinary 2,3-dinor-thromboxane B2 increased early in pregnancy (731 +/- 124 pg/mg creatinine) compared with nonpregnancy (less than 350 pg/mg creatinine; p less than 0.001) and the postpartum period (155 +/- 42 pg/mg creatinine, p = 0.015) and remained elevated throughout gestation. Similarly, plasma and urinary 11-dehydro-thromboxane B2 were increased in pregnancy. To determine the cellular origin of the increase in thromboxane biosynthesis in pregnancy, platelet cyclooxygenase was selectively inhibited with aspirin in a dose of 120 mg orally followed by 20 mg twice daily for 7 days (n = 4). Selectivity was confirmed by measurement of urinary 2,3-dinor-6-keto-prostaglandin F1 alpha, an index of prostacyclin biosynthesis. Coincident with a 97% inhibition of serum thromboxane B2, urinary 2,3-dinor-thromboxane B2 was almost completely inhibited and paralleled the recovery of platelet cyclooxygenase after withdrawal of aspirin. This study demonstrates that thromboxane biosynthesis is increased in pregnancy. The increase is mainly platelet derived and is consistent with increased platelet activation throughout pregnancy.     

The influence of population structure on systemic antibiotic consumption. Valladolid,Spain

BACKGROUND: The high degree to which systemic antibiotics are consumed in our country makes a study of those factors determining the spread thereof necessary. Different parameters are involved in the unequal spread of their consumption, including: a) the epidemiology of the infectious processes b) the population-dependent factors and c) factors depending upon the prescribing physicians. This study is aimed at analyzing those determining factors depending upon the population (type of population and age). METHODS: A longitudinal retrospective study based on systemic antibiotic consumption data provided by the company International Marketing Services (IMS) for the January 1, 1996-December 31, 2000 period. The consumption indicator used was the number of daily doses defined per 1000 inhabitants/day (DID). Six geographical areas in the province of Valladolid were placed under study, three of which were urban and the other three mainly rural. RESULTS: The overall consumption by area was as follows: Medina del Campo (25.9DID), the capital city of Valladolid (23.4DID), Laguna de Duero (22.6DID), Northern Area (22.4DID), Southern Area (21.4DID) and, lastly, the Central Area (20.2DID). The specific consumption by areas revealed a greater consumption of amoxicillin in the three urban areas, amoxicillin-clavulanic acid and the major macrolides in Medina del Campo, quinolone antibiotics in the Northern Area and tetracyclines and sulfonamides in the capital city of Valladolid. CONCLUSIONS: Major overall consumption-related differences were found to exist among areas, the maximums being found in the urban areas. These differences were more marked on when studying the geographic spread of the consumption of the main active ingredients.     

Platelet factor 4 promotes adhesion of hematopoietic progenitor cells and binds IL-8: novel mechanisms for modulation of hematopoiesis

Platelet factor 4 (PF4) is an abundant platelet alpha-granule C-X-C chemokine that has weak chemotactic potency but strongly inhibits hematopoiesis through an unknown mechanism. We find that PF4 binds to human CD34+ hematopoietic progenitor cells (HPCs) with a median effective concentration of 1 microg/mL but not after exposure to chondroitinase ABC. PF4 enhances adhesion of HPCs to intact stroma. Committed progenitors also adhere avidly to immobilized PF4. This adhesion is time-dependent, requires metabolic activity, causes cytoskeletal rearrangement, and induces cell-cycle inhibition. Using extracellular acidification rate to indicate transmembrane signaling, we find that interleukin-8 (IL-8), but not PF4, activates CD34+ progenitors, and PF4 blocks IL-8-mediated activation. Surface plasmon resonance analysis shows that PF4 binds IL-8 with high (dissociation constant [Kd] = 42 nM) affinity. Nuclear magnetic resonance analysis of IL-8 and PF4 in solution confirms this interaction. We conclude that PF4 has the capacity to influence hematopoiesis through mechanisms not mediated by a classical high-affinity, 7-transmembrane domain chemokine receptor. Instead, PF4 may modulate the hematopoietic milieu both directly, by promoting progenitor adhesion and quiescence through interaction with an HPC chondroitin sulfate-containing moiety, and indirectly, by binding to or interfering with signaling caused by other, hematopoietically active chemokines, such as IL-8.     

Direct findings of aortic injury on contrast-enhanced CT in surgically proven traumatic aortic injury: a multi-centre review

OBJECTIVE: To review the contrast-enhanced CT findings in surgically proven traumatic aortic injury (TAI). MATERIALS AND METHODS: We searched the trauma registries of three academic medical centres from 1994 to 2000 and found 34 patients with surgically proven TAI that received pre-operative contrast-enhanced chest CT. Two chest radiologists recorded by consensus the size and location of direct (pseudoaneurysm, intimal flap) and indirect (mediastinal haematoma) findings of TAI. The imaging findings were correlated with surgical reports. RESULTS: Direct findings of aortic injury (pseudoaneurysm or intimal flap) were seen on contrast enhanced CT in all patients and confirmed at surgery. Specifically, a pseudoaneurysm was seen in 33 (97%), presenting either as a focal bulge in 22 (65%) or as more diffuse aneurysmal enlargement in 11 (32%). An intimal flap was identified in 31 cases (91%). A periaortic haematoma was seen in 31 cases (91%). In the three patients without periaortic haematoma, the only indications of aortic injury were a focal pseudoaneurysm in two (6%) and an intimal flap in one (3%). CONCLUSION: In this series of surgically proven TAI, direct findings of aortic injury were seen in all cases. Aortic tear occurred without mediastinal haematoma in 9% (3/34) of patients.     

A retrospective analysis of long-term survival in severe aplastic anemia patients treated with allogeneic bone marrow transplantation or immunosuppressive therapy with antithymocyte globulin and cyclosporin A at a single institution

Severe aplastic anemia can be treated with either bone marrow transplantation (BMT) or immunosuppressive therapy (IST). A retrospective review of patients with severe aplastic anemia treated with both of these modalities was conducted. Fifteen BMT and 16 IST patients were available for analysis, and follow-up of 22 and 15 years was available for the BMT and IST groups, respectively. Median survival was limited to 4.3 months in BMT patients vs. 135.2 months in IST patients, despite the older median age of the latter (22 vs. 55 years). Actuarial survival at 1 and 5 years was 87% and 78% for the IST patients and 40% and 33% for the BMT patients. Hematologic response rates, as defined by achievement of transfusion independence, were similar for the two groups. Long-term responses and survival are possible with antithymocyte globulin/cyclosporin A.     

Post-therapeutic lymphedema: scintigraphy before and after autologous lymph vessel transplantation: 8 years of long-term follow-up

The function of lymphatic vessel grafts was proved in 12 patients with lymphedema of the upper extremity by visual and semiquantitative evaluation of a preoperative baseline study and scintigraphic follow-up data for a period of 8 years after microsurgical treatment. The transplantation site was an upper extremity. In 11 of 12 patients, lymphatic function improved after autologous lymphatic vessel transplantation compared with preoperative findings. This could be verified by a statistically significant decrease of the transport index ( < 0.01), clear demonstration of lymph nodes, and a less diffuse distribution pattern of the Tc-99m-labeled nanocolloids. In three patients, the vessel graft could be detected by scintigraphy. Lymphoscintigraphy combined with semiquantitative evaluation of lymphatic transport kinetics has been shown to be an easy and reliable method to assess lymphatic function before and after autologous lymph vessel transplantation.     

Reliability of treadmill measures and criteria to determine VO2max in prepubertal girls

PURPOSE: The main objective of this study was to determine the reliability of measuring treadmill exercise economy (VO2submax) and the maximal oxygen uptake (VO2max) in prepubertal girls tested twice, 6 wk apart. We also wanted to examine the percentage of young girls who were able to reach the criteria for achieving VO2max and to describe methods that would allow a high proportion of young children to achieve criteria for reaching a true VO2max. METHODS: We studied 61 normal-weight, prepubertal girls with a mean (+/- SD) age 7.3+/-1.3 yr (range 4.8 to 10.3 yr). VO2submax was determined while walking for 4 min at 2.5 mph with 0% grade. VO2max was measured during a progressive, all-out, continuous treadmill test using standardized procedures and criteria. Heart rate (HR) was measured using a Polar monitor. Respiratory rate (RR), respiratory exchange ratio (RER), ventilation (V), and VO2 were measured using a Sensormedics metabolic monitor. RESULTS: There were no significant differences between visits I and 2 in mean HR, RR, RER, V, VO2submax (421 vs 422 mL x min(-1), respectively), and VO2max (1036 vs 1049 mL x min(-1), respectively). Intra-individual coefficients of variation (CV) between visits 1 and 2 for submaximal tests were: HR = 5.1%, RR = 12.4%, RER = 7.2%, V = 12.5%, and VO2 = 12.4%. Intra-individual CVs for the maximum tests were: HRmax = 2.1%, RRmax = 10.8%, RERmax = 5.3%, Vmax = 11.7%, and VO2max = 7.5%. A high proportion of the girls reached criteria for VO2max [RER> 1.00, HR>85% of age predicted maximum, and plateauing of VO2max] in both visits: 99% reached one of three criteria, 92% reached two of three criteria, and 70% reached all three criteria. Twenty girls [mean age 7.2+/-1.2 yr] reached at least two criteria in both visits, whereas 32 girls [mean (+/- SD) age 8.6+/-1.0 yr] reached three criteria in both visits. CONCLUSION: Exercise measurements using treadmill testing were reliable in healthy, normal-weight, prepubertal girls. Older girls when compared to the younger girls were able to reach criteria for VO2max more often. Thus, we recommend that one testing should give researchers an accurate measure of walking economy and aerobic capacity, and that two criteria are enough for determining VO2max.