Efficacy of tranexamic acid for the prevention of bleeding in patients with von Willebrand disease and Glanzmann thrombasthenia: a controlled, before and after trial.

INTRODUCTION: Reducing bleeding episodes is very important in haematology disorders like von Willebrand disease (VWD) and Glanzmann thrombasthenia (GT). Replacement factors are very expensive although prophylactic drugs are affordable. OBJECTIVE: To study the prophylactic effects of tranexamic acid (TXA) for reduction of bleeding episodes in patients with VWD and GT in non-invasive conditions. METHODS: A controlled, double-blind before and after single-centre trial was performed in Amir-Kabir Hospital (Arak, Iran). The study was done on 17 patients with VWD and three patients with GT with minimum age of 2 years. Patients were received placebo for 6 months to evaluate the frequency and severity of bleeding and also to record the frequency of use of factor concentrates and platelet transfusion. After that, patients were given oral single dose of TXA 25 mg kg(-1) day(-1) for 6 months. The mentioned outcomes were studied and compared between two phases of study. Safety assessment was done in all patients. RESULTS: Tranexamic acid caused a significant reduction in number of Grade 1 and Grade 2 bleeding episodes in VWD patients (P < 0.001 and P < 0.01 respectively). In addition, TXA therapy was associated with significant decrease in the use of factor concentrates (P < 0.05). Number of bleeding episodes decreased in GT patients who used TXA; however, difference between two phases of studies was not significant (P = 0.1). TXA had no effect in the frequency of platelet transfusions in GT patients. TXA therapy was associated with headache, back pain and musculoskeletal pain. No case of allergy or thromboembolic events was seen following treatment. CONCLUSIONS: The results suggest that TXA is safe and effective to reduce bleeding and use of factor concentrates in VWD patients. In addition, TXA therapy can decrease bleeding in GT patients.

Effect of Chewing Gum on Oral Mucositis in Children Undergoing Chemotherapy: A Randomized Controlled Study.

BACKGROUND: Oral mucositis is an adverse effect of chemotherapy. Type of chemotherapy regimen is the most important factor causing mucositis. Oral mucositis is usually associated with transient decrease in saliva production. The goal was to study effects of gum consumption on oral mucositis in children undergoing chemotherapy. MATERIALS AND METHOD: This randomized controlled trial was done in Amir Kabir Hospital, Arak, Iran. 130 children 5 to 15 years of age were studied. Control group was composed of 65 children who received mucotoxic drugs. Test group was made up of 65 patients received similar drugs in addition to sugar free gums. Patients consumed 6 pieces of gums per day for 15 days. A standardized follow up form and World Health Organization (WHO) grading system for oral mucositis were used for evaluation of patients during 15 days of treatment. RESULTS: Severe oral mucositis occurred in 30 (46%) of 65 patients in the test group and in 26 of 65 (40%) patients in the control group. Difference was not statistically significant (P > 0.05). Rate of mild to moderate mucoitis (grade 1 and 2) was significantly lower in patients who used gums (15 % vs. 35%, P < 0.05). CONCLUSION: Our study showed that stimulation of saliva flow by chewing gum could decrease mild to moderate inflammatory injuries of the oral mucosa during chemotherapy. However, it was not effective to subside severe mucositis.

Association between serum ferritin level and diastolic cardiac function in patients with major ß-thalassemia.

BACKGROUND: Prevention of myocardial siderosis is a key step to reduce rate of mortality in thalassemic patients. Our objective was to study association between echocardiography parameters and serum ferritin level in patients with major thalassemia. MATERIALS AND METHODS: Sixty-six patients with major thalassemia were studied in Amir Kabir hospital, Arak, Iran. Serum ferritin levels were measured during 3 months in patients with no symptoms of infection. It was measured by enzyme-linked immunosorbent assay (ELISA). Ejection Fraction (EF), Fractional Shortening (FS) and Early/Late ratio (E/A) were studied by echocardiography. RESULTS: Fifty two percent were female and 48% were male. Mean age was 16 ± 9 years and the age range was3-26years. Mean serum ferritin level was1912 ± 1748 ng/dl and its range was from 303 to 8333 ng/dl. There were significant correlations between serum ferritin level and EF(r=0.3 and P=0.05) and also between serum ferritin level and FS. CONCLUSION: Due to significant association between serum ferritin level and echo parameters, it is beneficial that all patients with major thalassemia undergo echocardiography to gain better understating about cardiac function.

Efficacy and Safety of Sufentanil and Pethidine in Spinal Anesthesia for Painless Labor.

Saddle spinal is a reliable method for control of pain during labor. This method has rapid onset and causes complete sensory block without significant influence on motor neurons.Our goal was to compare the analgesic efficacy and side effects of pethidine and sufentanil via saddle spinal administration during labor.600 parturients requesting analgesia were randomly divided into 2 groups. First group was composed of 300 patients received 0.4 mg/kg pethidine and the second group was composed of 300 patients received 0.1 µg/kg sufentanil. Then, analgesia according to Visual Analogue Scale (VAS), itching, nausea, apnea and urinary retention were examined between 2 groups.VAS=3 was noted in both groups. Equal rate of apnea was seen in both groups. Patients received pethidine showed significantly a higher rate of nausea compared with sufentanil group (P<0.0001). Pruritus was significantly higher in patients received sufantanil (P<0.0001).Our findings suggest that saddle spinal by pethidine or sufentanil causes a considerable analgesia for labor. Proper management of the untoward effects of this method may introduce it as a safe and low-cost method for painless labor.

Association between serum ferritin level, cardiac and hepatic T2-star MRI in patients with major ß-thalassemia.

BACKGROUND: Frequent blood transfusion is often associated with iron overload. Proper use of iron chelators to treat iron overload requires an accurate measurement of iron levels. Magnetic resonance T2-star (T2* MRI) can measure iron level in the heart and liver. Our goal was to see whether an association exists between serum ferritin level and T2* MRI in patients with major beta thalassemia. MATERIALS AND METHODS: Sixty patients with a diagnosis of major beta thalassemia were enrolled in the study. They were older than five years old and needed regular transfusion. Cardiac and hepatic T2*MRI and mean serum ferritin levels were measured within 3 months. RESULTS: No significant correlation was observed between serum ferritin level and cardiac T2*MRI (p=0.361, r=-0.120).However, a significant correlation was observed between serum ferritin and liver T2*MRI (p=0.021, r=-0.297). CONCLUSION: Our results showed an association between hepatic T2*MRI and serum ferritin level.

Effect of metformin on miscarriage in pregnant patients with polycystic ovary syndrome / Efecto de la metmorfina sobre los abortos espontáneos de pacientes embarazadas que presentan el síndrome de ovario poliquístico

BACKGROUND: This study was performed with the aim of evaluating the effect of metformin in reducing miscarriage when continued until the end of the first trimester of pregnancy in patients with polycystic ovary syndrome (pCOS) and infertility. SUBJECTS AND METHOD: From January 2004 to December 2005, a total of 75 pregnant women with PCOS were studied in three different groups. In Group A, metformin administration (500 mg three times daily (TDS)) was stopped immediately after diagnosis of pregnancy (5-6 weeks gestation), in Group B, metformin was administered until the end of 8 weeks gestation and in Group C until the end of 12 weeks gestation. The results of this study were then assessed using chi-square McNemar's, ANOVA Kruskal Wallis and logistic regression tests. RESULTS: There was a significant statistical difference between previous and current miscarriage in the current pregnancy with a decline in Group B from 40% to 8% and in group C from 32% to 4%. In spite of the reduced rate of miscarriage seen in Group A, from 20% to 4%, this difference was not statistically significant. Fetal anomalies were absent in all three groups. CONCLUSION: According to the current findings, it seems that continuing metformin during the first trimester of pregnancy has beneficial effects in patients with PCOS.

ANTECEDENTES: Este estudio fue realizado con el propósito de evaluar el efecto de la metmorfina en la reducción de abortos espontáneos cuando se la continúa hasta el final del primer trimestre de embarazo, en pacientes con síndrome de ovario poliquístico (SOPQ) e infertilidad. SUJETOS Y MÉTODO: De enero 2004 a diciembre 2005, fueron estudiadas en tres grupos diferentes, un total de 75 mujeres embarazadas que presentaban SOPQ. En el grupo A, la administración de metmorfina (TDS) 500 mg tres veces al día se detuvo inmediatamente después del diagnóstico del embarazo (5 - 6 semanas de gestación); en el grupo B, se administró la metmorfina hasta el final de las 8 semanas de gestación, y en el grupo C hasta el final de las 12 semanas de gestación. Los resultados de esta estudio fueron entonces evaluados usando chi-cuadrado McNemar's, ANOVA Kruskal Wallis y teste de regresión logística. RESULTADOS: Hubo una diferencia estadística significativa entre los abortos espontáneos previos y los corrientes en los embarazos corrientes, con una disminución del 40% al 8% en el grupo B, y del 32% al 4% en el Grupo C. A pesar de la reducción de la tasa de abortos espontáneos observada en el grupo A, del 20% al 4%, la diferencia no fue estadísticamente significativa. Las anomalías fetales estuvieron ausentes en los tres grupos. CONCLUSIÓN: De acuerdo con los hallazgos actuales, parece que la continuación de la metmorfina durante el primer trimestre del embarazo, tiene efectos beneficiosos en los pacientes con SOPQ.

Effect of metformin on miscarriage in pregnant patients with polycystic ovary syndrome.

BACKGROUND: This study was performed with the aim of evaluating the effect of metformin in reducing miscarriage when continued until the end of the first trimester of pregnancy in patients with polycystic ovary syndrome (PCOS) and infertility. SUBJECTS AND METHOD: From January 2004 to December 2005, a total of 75 pregnant women with PCOS were studied in three different groups. In Group A, metformin administration (500 mg three times daily (TDS)) was stopped immediately after diagnosis of pregnancy (5-6 weeks gestation), in Group B, metformin was administered until the end of 8 weeks gestation and in Group C until the end of 12 weeks gestation. The results of this study were then assessed using chi-square McNemar's, ANOVA Kruskal Wallis and logistic regression tests. RESULTS: There was a significant statistical difference between previous and current miscarriage in the current pregnancy with a decline in Group B from 40% to 8% and in group C from 32% to 4%. In spite of the reduced rate of miscarriage seen in Group A, from 20% to 4%, this difference was not statistically significant. Fetal anomalies were absent in all three groups. CONCLUSION: According to the current findings, it seems that continuing metformin during the first trimester of pregnancy has beneficial effects in patients with PCOS.

Identification of mutations in the COL7A1 gene in a proband with mild recessive dystrophic epidermolysis bullosa and aortic insufficiency.

We report the clinical and molecular findings in a patient with a mild form of recessive dystrophic epidermolysis bullosa and aortic insufficiency. To our knowledge, this is the first report of association between dystrophic epidermolysis bullosa and abnormalities of the aortic valve. Analysis of the COL7A1 gene has revealed two new mutations, a 20-bp duplication and a splice site mutation.

Systemic antifungal therapy.

Systemic antifungal therapy for superficial mycoses has advanced greatly since the introduction of griseofulvin in 1958. The discovery of the azole antifungal compounds, ketoconazole, itraconazole, and fluconazole, allowed for a broader spectrum of treatment and a shorter treatment duration. Terbinafine, through a unique mechanism of action, has a fungicidal power not seen previously in the other antifungals. It is important to use our knowledge of the pharmacology in combination with clinical experience and cost of therapy in order to select the proper drug. The search to identify new oral antifungal agents should continue, since none of the five currently used drugs fulfill the criteria of the "ideal" antifungal.

TCR Vbeta expression in the small bowel of patients with dermatitis herpetiformis and gluten sensitive enteropathy. Limited expression in dermatitis herpetiformis and treated asymptomatic gluten sensitive enteropathy.

Dermatitis herpetiformis (DH) is a blistering skin disease characterized by cutaneous deposits of IgA and an associated, most often asymptomatic, gluten sensitive enteropathy (GSE). Gluten sensitive enteropathy is also seen in patients that do not have skin disease or cutaneous IgA deposits, but do have significant gastrointestinal (GI) complaints. Patients with DH and with GSE without skin disease have similar small bowel morphologic changes and HLA associations and both the skin disease and the GI symptoms can be controlled by a gluten free diet. It is not known what factors allow almost all patients with DH to continue to eat gluten and not develop symptomatic gastrointestinal disease. We have examined the expression of the Vbeta T-cell receptor (TCR) in the small bowel of patients with DH (n=11) and of patients with both symptomatic (n=10) and asymptomatic (n=7) GSE without skin disease to determine if differences in the pattern of TCR Vbeta expression are associated with differences in the clinical manifestations of these diseases. TCR Vbeta expression was analyzed using RT-PCR from small bowel biopsies. Patients with DH and those with GSE without skin disease that were on a gluten free diet and asymptomatic were found to express 6.6 and 5.6 out of 20 Vbeta families respectively, with no single family preference. Examination of peripheral blood lymphocytes from these patients did not reveal any restriction of TCR Vbeta family expression. In contrast, patients with symptomatic GSE expressed 12.6 Vbeta families (P< 0.05), with no consistent preferential expression of any single Vbeta family between patients. Patients with DH, who are continuing to ingest wheat, show a more restricted pattern of TCR Vbeta utilization, similar to that of treated patients with GSE without skin disease, and significantly different from GSE without skin disease patients eating gluten. These findings suggest that the restricted nature of the TCR Vbeta expression may play a role in the different clinical manifestations of dermatitis herpetiformis and isolated gluten sensitive enteropathy.

Expression of interleukin-4 and interferon-gamma in the small bowel of patients with dermatitis herpetiformis and isolated gluten-sensitive enteropathy.

Although possessing a morphologically similar small bowel abnormality to patients with isolated gluten-sensitive enteropathy (GSE), patients with dermatitis herpetiformis (DH) have few gastrointestinal symptoms and exhibit blistering skin lesions and cutaneous IgA deposits. To determine whether clinical discrepancies between these gluten-sensitive conditions might be the result of different patterns of small bowel cytokine expression, duodenal biopsies were obtained from eight DH patients and nine isolated GSE patients. Biopsies were evaluated for interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) expression by reverse-transcriptase polymerase chain reaction (message) and immunohistochemistry (protein). In DH patients, most of whom had no gut symptoms, IFN-gamma mRNA expression was significantly less than in isolated GSE patients with symptomatic gut disease. Conversely, IL-4 mRNA expression in DH patients was greater than that found among isolated GSE patients. These findings suggest that the different clinical phenotypes of gluten sensitivity may be caused by variation in cytokine expression in the small bowel response to gluten.

Prediction of outcome of patients with life-threatening ventricular arrhythmias treated with automatic implantable cardioverter-defibrillators using SPECT perfusion imaging.

BACKGROUND: In the present study, we examined the predictors of outcome of 103 patients with coronary artery disease and left ventricular dysfunction who had life-threatening ventricular arrhythmias and were treated with implantable cardioverter-defibrillators with the use of single-photon emission computed tomography (SPECT). METHODS AND RESULTS: During a mean follow-up of 29 months, there were 29 cardiac deaths. In comparison with patients who died, survivors had less diabetes mellitus (45% versus 19%, P < .007), higher left ventricular ejection fraction (23 +/- 9% versus 27 +/- 11%, P = .04), and fewer perfusion defects as determined with stress SPECT (15 +/- 5 versus 12 +/- 5, P < .004). Most of the perfusion defects were fixed, indicative of scarring; the extent of reversible defects did not differ (2 +/- 3 in survivors and 3 +/- 4 in nonsurvivors). Multivariate Cox survival analysis identified the number of fixed defects as the only independent predictor of death (chi 2 = 10, P = .002). There were six deaths among 42 patients (14%) with < 8 fixed defects compared with 23 deaths among 61 patients (38%) with > or = 8 defects (P = .005). The 4-year survival was better in patients with < 8 segmental fixed defects than in those with > or = 8 fixed defects (80% versus 36%) (chi 2 = 8, P = .005). CONCLUSIONS: The myocardial perfusion pattern is an important determinant of outcome in patients with life-threatening ventricular arrhythmias who are treated with a implantable cardioverter-defibrillator. The extent of scarring separates patients into high- and low-risk groups with a 2.7-fold difference in death rate.

Prognostic value of stress myocardial perfusion single photon emission computed tomography imaging in patients with left ventricular bundle branch block.

BACKGROUND: Left bundle branch block (LBBB) may occur with or without structural heart disease. In patients with coronary artery disease the presence of LBBB is associated with an increased risk of cardiovascular events. METHODS AND RESULTS: This study examined the outcome of 293 medically treated patients with LBBB and symptoms who were undergoing stress thallium-201 single photon emission computed tomography imaging. One hundred seventy-three men and 120 women with an age range of 67 +/- 9 years and a pretest probability of coronary artery disease of 77% +/- 28% were studied. During a mean follow-up of 33 months 58 hard cardiac events (death or nonfatal myocardial infarction) and 112 total events (hard events, coronary angioplasty, coronary bypass surgery, or cardiac transplantation) occurred. Univariate and multivariate Cox survival analysis with clinical, stress, hemodynamic, and single photon emission computed tomography variables identified the perfusion defect size (chi square = 27, p = 0.0001) and increased lung thallium uptake as the most important independent predictors of hard or total cardiac events. The hard event-free survival rate was 91% in patients with no or small defects (<15% of left ventricular myocardium) and 72% in patients with large defects (p = 0.0001, RR = 3.2, 95% CI 1.7 to 5.9). The total event-free survival rate was 81% in patients with small defects and 48% in patients with large defects (p = 0.0001, RR = 2.7, 95% CI 1.9 to 4.0). The total event rate was 54% in patients with large perfusion defects and increased lung uptake and 17% in patients with no or small abnormality and normal lung thallium uptake (p = 0.0001). CONCLUSION: Single photon emission computed tomography perfusion imaging is useful in predicting outcome in patients with LBBB and intermediate pretest probability of coronary artery disease. The size of perfusion abnormality and lung thallium uptake stratified patients into high and low risk groups with a threefold difference in hard and total cardiac events.

Utility of stress single-photon emission computed tomography (SPECT) perfusion imaging in predicting outcome after coronary artery bypass grafting.

Previous studies have examined the predictors of outcome in medically treated patients with coronary artery disease (CAD). There is limited information on predictors of outcome after coronary artery bypass grafting (CABG). This study examined the predictors of outcome of 255 patients with CAD, at a mean time of 5 years after CABG for angina pectoris. The 255 patients underwent coronary angiography and stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging after CABG. During a mean follow-up of 41 +/- 28 months after stress testing, there were 34 hard events (24 cardiac deaths and 10 nonfatal myocardial infarctions). The hemodynamics during stress testing, and age and gender were not predictors of events. The SPECT variables of multivessel perfusion abnormality, perfusion deficit size, and increased lung thallium uptake were predictors of death and total events by uni- and multivariate survival analysis. There were 14 events in 45 patients (31%) with multivessel abnormality and increased lung thallium uptake, 14 events in 101 patients (14%) with either multivessel abnormality or increased lung uptake, and 6 events in 109 patients (6%) with neither of these 2 variables (p = 0.0001). The annual mortality and total event rates were 7.5% and 9.5% with both variables, 3.4% and 4.3% with either variable, and 0.6% and 1.7% with neither of the variables (p = 0.01). Thus, stress SPECT perfusion imaging is useful to stratify patients after CABG into low, intermediate, and high risk groups for future cardiac events.