Relationship between control of ventricular rate in atrial fibrillation and systemic coagulation activation in patients with mitral stenosis

BACKGROUND AND AIM OF THE STUDY: Systemic thromboembolism is a major complication in patients with mitral stenosis (MS), especially in those who have atrial fibrillation (AF). It has been suggested that systemic coagulation activity may be increased in these patients. The study aim was to investigate the relationship between control of ventricular rate and systemic coagulation factors in patients with MS and AF by measuring plasma levels of prothrombin fragment (PF) 1+2, thrombin-antithrombin III complex (TAT) and plasminogen activator inhibitor-1. METHODS: Fifty-four consecutive patients with moderate to severe MS and AF were included in the study. Patients with resting heart rates < 100 beats per min were considered as having a controlled ventricular response rate (group A; n = 28) and those with > 100 beats per min as an uncontrolled ventricular response rate (group B; n = 26). RESULTS: Group A patients had a lower mean mitral gradient and pulmonary artery pressure than group B patients (11 +/- 6 versus 15 +/- 5 and 35 +/- 7 versus 39 +/- 8; p < 0.05, respectively). Plasma concentrations of PF 1+2 (4.17 +/- 2.1 versus 2.95 +/- 1.21; p < 0.01) and TAT III (4.61 +/- 1.75 versus 3.12 +/- 1.01; p < 0.01) were elevated in group B compared with group A. Similarly, group B patients had higher plasminogen activator inhibitor-1 levels than group A patients (7.87 +/- 3.8 versus 5.8 +/- 2.9; p < 0.05). A significant correlation was found between heart rate and plasma PF 1+2 and TAT levels. Multiple logistic regression analysis revealed that heart rate and mean mitral gradient were independent predictors of systemic coagulation activation. CONCLUSION: Besides contributing towards hemodynamic and symptomatic relief, the control of AF rate in MS patients induces a drastic decline in coagulation activation, and may also reduce the incidence of thromboembolism.     

Autologous bone marrow transplantation using marrow incubated with Asta Z 7557 in adult acute leukemia

The sensitivity of human myeloblastic leukemic (CFU-L) and normal hemopoietic stem cells (CFU-GM and BFU-e) to Asta Z 7557 (INN Mafosfamide) was studied with regard to autologous bone marrow transplantation (ABMT) with cleansed marrow for consolidation therapy in adult patients with acute leukemia (AL) in remission. Establishment of the dose-response curves for CFU-GM (n = 37), BFUe (n = 11), and myeloblastic CFU-L (n = 9) demonstrated a wide range of sensitivity from patient to patient for all three progenitors. Whereas CFU-L, CFU- GM, and BFU-e grown in semisolid cultures disclosed similar sensitivities to Asta Z 7557, long-term culture (LTC) studies (n = 41) indicated a higher resistance of early progenitors. In an effort to achieve a maximum tumor cell kill and yet spare a sufficient amount of normal stem cells to ensure consistent engraftment, we defined the optimal dose for marrow cleansing as the dose sparing 5% CFU-GM (LD95). This dose was established from a preincubation test (PIT) realized on a 10-mL marrow aspirate taken 15 days before marrow collection in each individual patient. Twenty-four adult patients while in remission of AL (20 in complete remission, four in partial remission) were consolidated by cyclophosphamide 60 mg/kg X 2 and total body irradiation at 10 Gy followed by ABMT with marrow cleansed by Asta Z 7557 according to the specification described above. Patients were divided in two groups: group 1, unfavorable prognosis (11 patients); group 2, standard prognosis [13 patients in first complete remission (CR)]. All patients engrafted on leukocytes (median day for recovery to 10(9)/L: day 30), patients with ALL recovered faster than patients with ANL (median day 19 v 34). Similarly, recovery of platelets to 50.10(9)/L occurred sooner in patients with ALL (median day 67, range day 23 through 90) whereas three patients with acute nonlymphoblastic leukemia (ANLL) in group 2 had to be supported with platelet transfusions for more than one year. In group 1, six patients had recurrent tumor within six months; three patients died from toxicity with no evidence of tumor. Two patients are still disease-free with a short follow-up (nine and ten months). In group 2, two patients died from toxicity with no evidence of leukemia three and 16 months post-ABMT. One patient with a M5 ANLL and one patient with ALL relapsed at six and 15 months, respectively. Nine patients have remained in CR or are disease-free with a median follow-up of 22 months.(ABSTRACT TRUNCATED AT 400 WORDS)     

Correlation between infarct-related coronary artery patency and predischarge electrocardiographic patterns in patients with first anterior myocardial infarction who received thrombolytic therapy

The aim of this study was to investigate the correlation between the ST-segment and T-wave patterns in predischarge electrocardiogram and patency of left anterior descending coronary artery in patients with a first anterior myocardial infarction (AMI). One hundred and fifty-six of 175 consecutive patients who were admitted to our clinic between January 2000 and September 2002 due to a first episode of transmural AMI and who received thrombolytic therapy were enrolled. Coronary angiography was performed by the Judkins method on the 6th–10th day after the acute infarction. The corrected TIMI frame count (CTFC) was estimated according to the previously described method. According to the combination of the ST-segment and T-wave morphology on the day (6–10) of cardiac catheterization, patients were classified into four groups: group A, ST elevation 0.1mV and negative T waves; group B, ST elevation 0.1mV and negative T waves; group C, ST elevation 0.1mV and positive T waves; and group D, ST elevation 0.1mV and positive T waves. Of the 99 patients with negative T waves, 47 (48%) had CTFC 27, 32 (32%) CTFC between 27 and 40, 15 (15%) CTFC 40–100, and 5 (5%) CTFC 100. Of the 57 patients with positive T waves, CTFC was 27 in 14 (25%), between 27 and 40 in 17 (30%), 40–100 in 11 (19%), and 100 in 15 (26%) (P 0.001). From the 76 patients with an isoelectric ST segment, 38 (50%) had CTFC 27, 29 (38%) CTFC between 27 and 40, 8 (11%) CTFC 40–100, and 1 (1%) CTFC 100. Of the 80 patients with an elevated ST segment, 23 (29%) had CTFC 27, 20 (25%) CTFC between 27 and 40, 18 (23%) CTFC 40–100, and 19 (23%) CTFC 100 (P 0.001). Use of the combination of two electrocardiographic parameters (ST segment and T waves) also indicated that there were significant differences between groups A and D, and groups B and D (P 0.001 and P 0.05, respectively). Development of an isoelectric ST segment with negative T waves may indicate a better degree of reperfusion after AMI. In contrast, patients in whom ST-segment elevation and positive T waves remain at discharge from the coronary care unit have a higher probability of a nonpatent left anterior descending artery.     

The changing role of the primary school teacher in Swaziland in the context of HIV/AIDS: teacher as caretaker and economic provider

Swaziland has the world''s highest HIV prevalence with 26% of adults aged 15–49 years living with HIV. There are approximately 17,000 Swazi children aged 0 to 14 years living with HIV. This qualitative study explored the experiences of Swazi teachers supporting learners living with or affected by HIV/AIDS, with a specific focus on the extent to which teachers are aware of the “Rights of the Child” in their teaching and approaches. Important themes emerged from thematic analysis including the following: teachers provided more than education to learners living with and affected by HIV, including material goods and additional time, in some cases at the expense of other learners. In the era of HIV/AIDS, the teacher has become the emotional caretaker and economic provider in addition to the predictable role of educator in Swaziland. Education curricula in HIV-burdened countries need to modify training programmes and support services available to teachers to accommodate the complex role that teachers play in caring for learners living with and affected by HIV.     

A cross-sectional survey of the diagnosis and management of bone metastasis in breast cancer patients in Turkey

Purpose

This study aimed to report the practice of managing breast cancer with bone metastasis in Turkey and to determine the adherence to the British Association of Surgical Oncology (BASO) guidelines.

Methods

This multicenter, cross-sectional epidemiological survey was conducted in 38 centers across Turkey. Data from 1,026 breast cancer patients with bone metastases (mean age 54.0?±?11.9 years) were analyzed.

Results

Over 30 % of patients had a diagnosis of metastatic breast cancer (stage IV) at the time of primary diagnosis. The imaging modalities used for diagnosing bone metastases were bone scintigraphy (57.8 %), radiography (22.8 %), and bone survey (4.4 %). Tumor markers were detected in 94.9 %, and markers of bone metabolism were measured in 90.4 % of patients. A total of 3.5 % of patients underwent surgery for bone metastasis, 26.4 % underwent palliative chemotherapy (most commonly docetaxel?+?capecitabine), and 56.5 % endured radiotherapy. Most patients (96 %) also received bisphosphonate. Radiography, bone scintigraphy, and CT were the main imaging tools used for postoperative follow-up of bone metastasis. Our results were >95 % in line with the BASO guidelines for the management of bone metastasis, except that interventional procedures, such as biopsy, were applied less frequently in our survey.

Conclusions

The diagnosis and management practices of breast cancer with bone metastasis in Turkey were generally compatible with international guidelines. However, the awareness and knowledge of physicians on the current guidelines should be increased, and equipment for the appropriate interventional procedures should be provided in every clinic to obtain optimal and standard management of bone metastases.     

Effect of infective endocarditis on blood coagulation and platelet activation and comparison of patients with to those without embolic events

Inflammation-induced procoagulant changes and alterations in platelet activity appear to play an important role in thromboembolic complications of infective endocarditis (IE). The aim of this study was to investigate systemic coagulation activity, fibrinolytic capacity, and platelet activation in IE patients with and without embolic events by measuring the plasma levels of prothrombin fragment 1 + 2, thrombin-antithrombin III complex, plasminogen activator inhibitor-1, beta-thromboglobulin, and platelet factor 4. The study included 76 consecutive patients with definite IE according to the Duke criteria. Among them, 13 (17.1%) had major embolic events. Plasma concentrations of prothrombin fragment 1 + 2 (3.2 +/- 1.3 vs 1.7 +/- 0.7 and 1.4 +/- 0.7 nmol/L, p <0.001, respectively) and thrombin-antithrombin (7.3 +/- 1.5 vs 2.9 +/- 1.2 and 2.2 +/- 1.1 ng/ml, p <0.001, respectively) were elevated in patients with embolic events compared with both patients without embolic events and control subjects. Similarly, patients with embolic events had increased plasma levels of beta-thromboglobulin (63.3 +/- 10.9 vs 33.1 +/- 11.6 and 19.1 +/- 10.6 ng/ml, p <0.001, respectively) and platelet factor 4 (106.0 +/- 28.7 vs 50.3 +/- 16.7 and 43.0 +/- 15.8 ng/ml, p <0.001, respectively) compared with those without embolic events and the control group. Embolic patients also had higher plasminogen activator inhibitor-1 levels than both nonembolic patients and healthy subjects (14.4 +/- 6.4 vs 8.6 +/- 5.9 and 5.4 +/- 4.3 ng/ml, p = 0.002, respectively). In conclusion, IE patients with subsequent thromboembolism have increased systemic coagulation activation, enhanced platelet activity/damage, and impaired fibrinolysis. The resulting imbalance produces a sustained hypercoagulable state that may contribute to the increased risk of thromboembolic events in this particular group.     

Marrow purging in autologous bone marrow transplantation for T-lineage acute lymphoblastic leukemia: efficacy of ex vivo treatment with immunotoxins and 4-hydroperoxycyclophosphamide against fresh leukemic marrow progenitor cells

A lymphoblast progenitor cell assay was used to evaluate the antileukemic efficacy of marrow-purging protocols that employed intact ricin immunotoxins (IT) and 4-hydroperoxycyclophosphamide (4-HC) against clonogenic primary T-lineage marrow blasts freshly obtained from 12 T-lineage acute lymphoblastic leukemia (ALL) patients. Residual T-lineage blast colonies were observed after treatment with 1 micrograms/mL T101 (anti-CD5)-Ricin (R) + G3.7 (anti-CD7)-R in eight of 12 cases and after 100 micrograms/mL 4-HC in six of nine cases. By comparison, a combination of IT and 4-HC proved very effective against T-lineage leukemic progenitor cells, and no residual blast colonies were observed in any of the eight cases studied. We conclude that future trials should consider combined treatment protocols such as IT + 4-HC for more effective purging of autologous marrow grafts.