Plasminogen deficiency

Journal of Thrombosis and Thrombolysis - Plasminogen plays an important role in fibrinolysis as well as wound healing, cell migration, tissue modeling and angiogenesis. Congenital plasminogen...     

Relationship between SP1 polymorphism and osteoporosis in β-thalassemia major patients

Background: β-Thalassemia is an autosomal recessive disease characterized by defective β-globin chain production. Osteoporosis is an important cause of morbidity in patients with β-thalassemia major. The pathogenesis of reduced bone mineral density (BMD) is multifactorial. A range of genetics factors have been implicated in other populations of patients with osteoporosis. Polymorphism at the Sp1 binding site of the collagen type I A1 ( COLIA1 ) gene is thought to be an important factor in the development of osteoporosis.
Methods: Alleles S and s , detected by presence of a G or T nucleotide, respectively in a regulatory site of the COLIA1 gene were investigated in 37 β-thalassemia major patients with osteoporosis and 92 controls without osteoporosis or osteopenia using polymerase chain reaction–restriction fragment length polymorphism.
Results: Fifteen and nine β-thalassemia major patients displayed SS and Ss genotypes, respectively, whereas 13 were found to have an ss genotype. The mean BMD of the β-thalassemia major patients with ss genotype was similar to those with the Ss and SS genotypes. In the control group, 77 and 15 subjects had SS and Ss genotypes, respectively, with no ss genotype. Allelic and genotypic distribution in patients were significantly different from controls.
Conclusion: Determining base substitutions at the Sp1 binding site on the COLIA1 gene in early years may be important in preventing osteoporosis in children with β-thalassemia major.     

Antibody titers and immune response to diphtheria-tetanus-pertussis and measles-mumps-rubella vaccination in children treated for acute lymphoblastic leukemia

The objective of this study was to investigate the diphtheria-tetanus-pertussis and/or measles-mumps antibody titers before and after vaccination at various time points of acute lymphoblastic leukemia (ALL) therapy and to suggest an appropriate vaccination approach for ALL patients. The authors studied 37 ALL patients and 14 healthy control subjects, divided into three groups. In group 1 (newly diagnosed patients), baseline anti-diphtheria, anti-tetanus, and anti-pertussis titers were determined. Patients in group 2 (on maintenance chemotherapy) and group 3 (patients not receiving therapy for 3-6 months) were vaccinated with diphtheria-tetanus with or without acellular pertussis; group 3 and control subjects were also given measles-mumps-rubella vaccine. Preimmunization and 1-month postimmunization titers were drawn. Preimmunization anti-diphtheria and anti-tetanus antibody titers between the groups and the controls were statistically similar. The seropositivity rate for anti-measles antibody in group 3 was significantly lower than controls. After vaccination, all of the patients developed protective anti-diphtheria and anti-tetanus antibody titers. The seroconversion rates of group 3 and controls for anti-measles and anti-mumps antibodies were statistically similar. The results showed that patients on maintenance therapy and after cessation of therapy made good antibody responses to diphtheria and tetanus toxoids, but response to measles and mumps vaccines was not as sufficient as toxoid vaccines. Children with ALL can receive the appropriate vaccines during and after maintenance treatment.     

Comparison of the effects of lornoxicam versus diclofenac in pain management after cardiac surgery: A single-blind, randomized, active-controlled study

Background:

Inadequate pain management after cardiac surgery may result 10 in increased morbidity and length of hospital stay. Although opioids are the mainstay of postoperative analgesia, nonsteroidal anti-inflammatory drugs (NSAIDs) may be used instead to avoid the adverse effects (AEs) associated with opioids. Lornoxicam is a newly developed NSAID, the use of which is increasing. However, lornoxicam has not been studied for use in pain management after cardiac surgery.

Objective:

The objective of this study was to compare the efficacy and tolerability 10 of lornoxicam and diclofenac sodium, an NSAID well established for use in pain management after major surgery, in pain management after coronary artery bypass grafting (CABG).

Methods:

This single-blind, randomized, active-controlled study was conducted 10 at the Gaziantep University Hospital, Gaziantep, Turkey. Adult patients scheduled to undergo valve or CABG surgery for the first time were included. Patients were premedicated with diazepam 10 mg PO at 10 PM on the evening before surgery. General anesthesia was induced using fentanyl, midazolam, and propofol, and maintained using fentanyl and isoflurane in pure oxygen. After extubation and when they stated that they felt pain, patients were randomly assigned to 1 of 2 treatment groups: lornoxicam 8 mg IM q8h or diclofenac 75 mg IM q12h, for 48 hours. Meperidine 1 mg/kg IM was given for additional analgesia when needed (rescue medication). Pain relief was assessed using an I1-point visual analog scale (0 = no pain to 10 = worst pain imaginable) immediately before the first injection (baseline), and at 15 and 30 minutes and 1, 2, 3, 4, 6, 12, 18, 24, and 48 hours after the first injection. Sedation was assessed using a 5-point scale (0 = awake and alert to 4 = deep sedation) at the same time points. Tolerability was assessed by monitoring of AEs using patient interview and laboratory analyses.

Results:

Forty patients were enrolled in the study (30 men, 10 women; 10 mean [SD] age, 54.4 [11.1 ] years; 20 patients per treatment group). The demographic and clinical characteristics and mean baseline pain relief scores were statistically similar between the 2 treatment groups. The mean pain relief scores at 15 and 30 minutes were statistically similar to baseline values in the 2 treatment groups. However, the mean pain relief scores at ≥1 hour after the first injection were significantly lower compared with baseline values (both groups, P < 0.05 at time points ≥1 hour). No significant between-group differences in mean pain relief scores were found at any time point. The overall mean pain relief scores were statistically similar between the 2 treatment groups. The mean sedation scores were significantly higher at 30 minutes, 1 hour, and 2 hours after the first injection in the diclofenac group compared with the lornoxicam group (all, P < 0.05). No AEs were observed. The need for rescue medication was statistically similar between the 2 treatment groups (lornoxicam, 2 patients; diclofenac, 3 patients).

Conclusions:

In this study of adult patients who underwent CABG, the efficacy 10 of lornoxicam and diclofenac were similar in postoperative pain management. Both study drugs were well tolerated.     

The effects of pentoxifylline on the myocardial inflammation and ischemia-reperfusion injury during cardiopulmonary bypass

BACKGROUND: Pentoxifylline (Ptx) decreases necessity of cell energy and inflammatory reactions via inhibition of 5'-nucleotidase (5'-NT). The aim of this study is to investigate whether the addition of Ptx into the cardioplegic solutions avoids myocardial inflammatory reactions and ischemia/reperfusion (I/R) injury during extracorpereal circulation. METHODS: Between December 1999 and February 2002, we operated 75 patients with the diagnoses of atrial septal defect (ASD), ventricular septal defect (VSD), valve disease, and coronary disease. The average age of patients was 42.4 and male-female ratio was 1: 1.5. The patients were divided into two groups, which were the study group (n = 40) and the control group (n = 35). We used cold blood cardioplegia mixed with St. Thomas' Hospital II cardioplegic solution for both of the groups. Ptx was added into the cardioplegic solution (500 mg/L) in the study group. Interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrotisis factor-alpha (TNF-alpha) levels in coronary sinus blood samples during cross-clamp time (X-clamp) and after releasing of it and tissue TNF-alpha in the right atrial appendix biopsy material that was taken after X-clamp were studied to compare the both groups. RESULTS: After releasing X-clamp, results of blood TNF-alpha, IL-6, and IL-8 of both groups were statistically significant (p < 0.005). At the pathological examination, we also observed that the amount of tissue TNF-alpha in the control group (66 +/- 17.1) was much higher than the study group (16.6 +/- 5.9, p <0.005). CONCLUSIONS: These results show that Ptx may be added into cardioplegic solution to avoid the myocardial inflammation and I/R injury during open heart surgery.     

Is Familial Mediterranean Fever a thrombotic disease or not?

The aim of our study was to show how the progression and severity of Familial Mediterranean Fever (FMF) is affected by procoagulant activity and alterations in the markers of thrombosis and fibrinolysis. The study cohort comprised 64 FMF patients who were classified as attack-free patients (Group 1; n = 34 patients, aged 3–19 years) and attack patients (Group 2; n = 30 patients, aged 3–21 years). All patients were on colchicine treatment with the exception the newly diagnosed patients in Group 2. A total of 14 healthy subjects between 5–12 years of age were enrolled as controls (Group 3). Laboratory tests, including leukocyte and thrombocyte counts, erythrocyte sedimentation rate, CRP, fibrinogen, PT, aPTT, Factor VIII, vW factor, D-dimer, P-selectin, tPA and PAI-1, were carried out on all patients. Inflammation continued both during the attack and attack-free period in FMF. The prolongation of PT was observed during attacks (PT = 13.6 s in Group 2, and PT = 12.6 s in Group 3; p = 0.002). tPA levels increased in FMF patients (tPA levels of group 1, 2 and 3 were 12.6, 13.2 and 9.7 ng/ml, respectively; p = 0.01). P-selectin was lower in both patient groups than in the control group. During attack periods PAI-1 levels increased (PAI-1 level of Group 1: 89.6 ng/ml and PAI-1 level of Group 2: 335.7 ng/ml, p = 0.000). Inflammation with increased acute phase reactants continued during both attack and attack-free periods in FMF patients. Prolongation of PT and differences in tPA and P-selectin levels suggest that hypercoagulability may have a role in the etiopathogenesis of FMF. It may be possible to use PAI-1 as a marker for the attacks of FMF. Presented at the International Hematology Congress, Istanbul 2005.     

Toxic epidermal necrolysis after the use of high-dose cytosine arabinoside

We report a fatal case of toxic epidermal necrolysis (TEN) resulting from a high dose of cytosine arabinoside (ARA-C). A 13-year-old girl with acute lymphocytic leukemia was treated according to the protocol of the BFM Group (BFM-95, HRG). On the fifth day after administration of a high dose of ARA-C (2 g/m2 intravenously every 12 hours), she developed bullous lesions on the hands and soles that disseminated, evolving to necrosis, sepsis, and death on the 22nd day. ARA-C is frequently associated with dermatologic toxicity, but this is only the second case of toxic epidermal necrolysis described in connection with this drug.