Effect of pramipexole on cutaneous-silent-period parameters in patients with restless legs syndrome

Objective

The aim of this study was to investigate cutaneous-silent-period (CSP) parameters in patients with restless legs syndrome (RLS) and examine the effects of treatment on CSP which, to our knowledge, have not been investigated till date.

Methods

A total of 25 patients with RLS and 25 healthy volunteers were studied. CSP latency and duration in the upper and lower extremities were examined in the two groups. In RLS patients, the variables were examined before and after pramipexole treatment.

Results

Lower-extremity CSP latency was longer (106.22 ± 11.69 ms vs. 91.67 ± 8.53 ms; p < 0.001) and CSP duration was shorter (35.50 ± 10.91 ms vs. 49.47 ± 6.43 ms; p < 0.001) in patients, compared with controls. In the patient group, CSP durations in the upper (40.88 ± 7.95 ms vs. 46.84 ± 10.22 ms; p = 0.006) and lower extremities (35.50 ± 10.91 ms vs. 44.91 ± 6.43 ms; p = 0.005) were prolonged after treatment, compared with pre-treatment values.

Conclusions

Small-fibre neuropathy may exist in RLS. In addition, we suggest that pramipexole may regulate cortical and spinal inhibitory mechanisms.

Significance

The use of CSP may aid in the diagnosis of RLS and may be used as a measure of treatment effectiveness.     

Efficacy and safety of pramipexole in chinese patients with restless legs syndrome: results from a multi-center, randomized, double-blind, placebo-controlled trial

Background

We performed a six-week study of pramipexole vs. a placebo in Chinese restless legs syndrome patients.

Methods

Overall, 305 enrolled patients were assigned randomly in a 2:1 ratio to the pramipexole group (N = 202) and the placebo group (N = 103).

Results

Of 287 patients in the full analysis set, the pramipexole group showed significant improvement compared with the placebo group in the change of their International Restless Legs Syndrome Study Group Rating Scale of Severity (IRLS) total score from baseline to week 6 after adjustment of centers and baseline characters (−15.87 ± 0.66 vs. −11.35 ± 0.92, p < 0.0001) and in the proportion of patients who were “much improved” and “very much improved” when measured by Clinical Global Impressions-Improvement (81.9% vs. 54.3%, p < 0.0001). At week 6, the IRLS responder rate was 73.8% (pramipexole) and 48.9% (placebo) (p < 0.0001) and the patient global impression responder rate was 68.6% (pramipexole) and 43.5% (placebo) (p < 0.0001). The proportion of adverse events was 62.9% in the pramipexole group and 43.7% in the placebo group, respectively. No deaths occurred.

Conclusion

Pramipexole was effective and well-tolerated in Chinese patients with restless legs syndrome.     

Comparison of the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depressive disorder

Objective

Only two-thirds of depressive patients respond to antidepressant treatment. In recent years, addition of an atypical antipsychotic drug to ongoing treatment with an antidepressant has been considered effective and well-tolerated. In the present study, we compared the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depression.

Subjects and methods

Twenty-four patients who met the DSM-IV criteria for major depressive disorder who did not at least two different classes of antidepressants were enrolled in the study. Nine were male and thirteen were female, and their ages ranged from 28 to 66 (mean ± SD = 39 ± 12) years. Patients were prescribed paroxetine (n = 11) or sertraline (n = 13) for 4 weeks. Then, those whose scores on the 17-item Hamilton Rating Scale for Depression (HAMD17) decreased below 50% received adjunctive therapy of aripiprazole for 4 weeks.

Results

Although the use of either combination treatment decreased the HAMD17 scores compared to the respective monotherapy, there was no significant difference in HAMD17 scores between the paroxetine plus aripiprazole group and sertraline plus aripiprazole group.

Conclusion

Aripiprazole augmentation therapy with paroxetine or sertraline was equally effective and tolerated in patients with refractory major depressive order.     

Serum brain-derived neurotrophic factor predicts responses to escitalopram in chronic posttraumatic stress disorder

Introduction

Some studies have found that antidepressants increase serum brain-derived neurotrophic factor (BDNF) levels in patients with major depression and the expression of BDNF mRNA in limbic structures of rats.

Objectives

This study addressed whether the SSRI escitalopram increases serum BDNF levels in subjects with PTSD and whether BDNF levels are associated with treatment response.

Methods

Medically healthy male subjects (N = 16) with chronic PTSD completed a 12 week open-label trial of flexible dose (5–20 mg/day) escitalopram monotherapy. BDNF levels were obtained at baseline, and at weeks 4, 8 and 12.

Results

PTSD symptoms significantly declined over the course of the 12 week escitalopram treatment. Despite a substantial improvement in PTSD symptoms, there was virtually no change in BDNF levels over time. Nevertheless, mean BDNF levels across the trial were strongly correlated with the slope of PTSD symptoms over the 12 weeks (r = 0.58, p = 0.018). Lower mean BDNF was associated with a greater decrease in PTSD symptoms over the course of the trial.

Conclusions

PTSD subjects with low BDNF levels demonstrated the largest treatment response from an agent with putative neurotrophic effects.     

Motor inhibition and cognitive flexibility in pathologic skin picking

Background

Individuals with pathologic skin picking (PSP) often report significant difficulty resisting the urges and drive to engage in picking behavior. Studies have shown significant inhibitory deficiencies (i.e. increased impulsivity) in subjects with other putative obsessive–compulsive spectrum disorders, such as trichotillomania, using objective tests. This study sought to assess motor inhibitory control and aspects of cognitive flexibility in a sample of individuals with PSP.

Method

Twenty subjects with PSP (mean age 33.1 ± 14.3 years; 85% female) and 20 healthy controls (mean age 31.6 ± 9.1 years; 85% female) underwent cognitive assessments using the Stop-signal and Intra-dimensional/Extra-dimensional (ID/ED) set-shift tasks. Groups were matched for age, gender, and education.

Results

PSP was associated with significantly impaired stop-signal reaction times but intact ID/ED cognitive flexibility compared to controls. Measures of disease severity in the PSP subjects did not covary significantly with stop-signal performance.

Conclusion

The finding of impaired inhibitory control but intact set-shift cognitive flexibility draws remarkable parallels with findings in trichotillomania but differs from obsessive compulsive disorder. These findings have important implications for understanding potential neurobiological dysfunction in PSP, how the disorder should be classified, and suggest new potential treatment directions.     

Restless legs symptoms in adolescents: Epidemiology,heritability, and pubertal effects

Aims

We aimed to determine the prevalence, pubertal effect, familial aggregation, and heritability of restless legs (RLS) symptoms in Chinese adolescents. In addition, the correlates and consequences of RLS symptoms were examined.

Methods

This was a population-based family study that involved 1549 adolescents (probands), their parents and siblings. RLS symptoms were assessed by a single question measuring the core features of RLS. Subjects with RLS symptoms for at least once per week were considered as abnormal. Impairment of daytime functions, behavioral problems, health status, and lifestyle practice were also documented.

Results

The prevalence of RLS symptoms was 2.8% in adolescents and 7.4% in their parents with female preponderance. Gender difference of RLS symptoms emerged in mid-pubertal adolescents (Tanner stage 3 or above). RLS symptoms were closely associated with various sleep problems (range of ORs = 2.24 to 32.5, p < 0.05), except habitual snoring. They were also independently associated with impairment of daytime functions, poor general health and frequent temper outbursts but not caffeine or alcohol intake or cigarette smoking after adjustment for age, sex, and other comorbid sleep problems. RLS symptoms presented with a modest familial aggregation and heritability (h² ± SE = 0.17 ± 0.04, p < 0.001).InterpretationRLS symptoms are common in Chinese adolescents with significant health repercussions. Puberty plays a critical role in the emergence of gender difference of RLS symptoms, which are accounted for by both genetic and environmental factors.     

Validation of the Chinese Non-Motor Symptoms Scale for Parkinson's disease: Results from a Chinese pilot study

Objectives

To evaluate a Chinese version of the Non-Motor Symptoms Scale (NMSS) in Parkinson's disease (PD) as an instrument for measuring non-motor symptoms (NMSs) in Chinese patients with Parkinson's disease.

Methods

We conducted a psychometric analysis of the Chinese version of NMSS using a cross-sectional study of 126 patients with PD. The battery also included the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Mini-Mental State Examination (MMSE), the Geriatric Depression Scale (GDS), and the Hamilton Anxiety Scale (HAMA), and was conducted by neurologists.

Results

There were significant correlations between the NMSS and PSQI scores (rS = 0.63, P < 0.001), as well as the NMSS and ESS scores (rS = 0.38, P < 0.001). Furthermore, significant positive correlations between NMSS and GDS, NMSS and HAMA, and NMSS and disease duration were also observed. Importantly, the sleep/fatigue index of the NMSS significantly correlated with the PSQI and ESS findings, the mood/cognition index of the NMSS significantly correlated with the GDS and HAMA findings, and the attention/memory index of the NMSS significantly correlated with the MMSE findings.

Conclusion

The Chinese version of the NMSS can be considered a comprehensive, useful measure for NMS evaluation in Chinese PD patients.     

Association of the manganese superoxide dismutase gene Ala–9Val polymorphism with clinical phenotypes and tardive dyskinesia in schizophrenic patients

Objective

Several recent studies that have investigated the genetic association between the manganese superoxide dismutase (MnSOD) gene Ala–9Val single-nucleotide polymorphism (SNP) and tardive dyskinesia (TD) have produced conflicting results. This study was to investigate whether this SNP was associated with clinical phenotypes and antipsychotic-induced tardive dyskinesia (TD) in schizophrenia in a genetically homogeneous Han Chinese inpatient population.

Methods

Genotyping was performed for the MnSOD gene Ala–9Val SNP in Chinese schizophrenia patients with (n = 176) and without TD (n = 346). The severity of TD was assessed using the abnormal involuntary movement scale (AIMS), and psychopathology using the Positive and Negative Syndrome Scale (PANSS).

Results

The frequencies of genotypes and alleles did not differ significantly between schizophrenic patients with and without TD (both p > 0.05). Also, there was no significant difference in the AIMS total score between the Val/Val and Ala allele carrier groups (p > 0.05). However, the PANSS negative symptom subscore was significantly higher in patients with Val/Val genotype (21.8 ± 7.3) than those with Ala alleles (20.1 ± 7.7) (t = 2.32, p = 0.03).

Conclusion

While the MnSOD gene Ala–9Val polymorphism did not play a major role in the susceptibility to TD in schizophrenic patients, it might be associated with negative symptoms of schizophrenia.     

Volumetric differences in the pituitary between drug-naïve and medicated male patients with obsessive–compulsive disorder

Objective

Obsessive–compulsive symptoms are induced or aggravated by stress, and the pituitary is a key component of the hypothalamic-pituitary-adrenal axis. We examined pituitary volume in drug-naïve and medicated male patients with obsessive–compulsive disorder (OCD).

Methods

Volumetric magnetic resonance imaging studies were conducted on 62 male control subjects, medicated male patients (N = 50) and drug-naïve male patients (N = 12) with OCD.

Results

Pituitary volume was significantly smaller in drug-naïve patients with OCD (464.97 ± 55.82 mm³) compared to medicated patients (577.84 ± 129.11 mm³, P = 0.004) and control subjects (543.04 ±113.70 mm³, P = 0.027), and no difference between control subjects and medicated patients (P = 0.174).

Conclusion

The results indicate that drug-naïve male patients with OCD exhibit decreased pituitary volume. This finding suggests that dysregulation of the HPA axis in OCD may influence pituitary volume. In addition, the increased pituitary volume in medicated patients may reflect the effect of drugs on the pituitary.     

Benefits from sustained-release pyridostigmine bromide in myasthenia gravis: Results of a prospective multicenter open-label trial

Introduction

For more than 50 years the acetylcholinesterase inhibitor pyridostigmine bromide has been the drug of choice in the symptomatic therapy for myasthenia gravis. The sustained-release dosage form of pyridostigmine (SR-Pyr) is only available in a limited number of countries (e.g. in the United States and Germany). Astonishingly, the therapeutic usefulness of SR-Pyr has not yet been evaluated.

Methods

In this non-interventional prospective open-label trial, 72 patients with stable myasthenia gravis were switched from instant-release dosage forms of pyridostigmine bromide to SR-Pyr. The results from the 37 patients younger than 60 years were separately analyzed.

Results

The initial daily dose of SR-Pyr was 288.1 ± 171.0 mg. The drug switch was unproblematic in all patients. The number of daily doses was significantly reduced from 4.3 to 3.6 (p = 0.011). The switch to SR-Pyr ameliorated the total quantified myasthenia gravis (QMG) score from 0.9 ± 0.5 to 0.6 ± 0.4 (p < 0.001) in all patients and in the younger subgroup. This was accompanied by a significant improvement in the quality of life parameters. The health status valued by EuroQoL questionnaire improved from 0.626 ± 0.286 to 0.782 ± 0.186 (p < 0.001). After switching to SR-Pyr, 28 adverse reactions disappeared and 24 adverse reactions occurred less frequent or weaker, however, 17 new adverse reactions were documented.

Conclusions

Our results support the usefulness of SR-Pyr in an individualized therapeutic regimen to improve quality of life regardless of the patient's age in myasthenia gravis.     

Subcutaneous Enoxaparin for Therapeutic Anticoagulation in Hemodialysis Patients

Background

Information regarding dosing of low-molecular-weight heparins (LMWH) for therapeutic anticoagulation in hemodialysis (HD) patients is limited. The aim of this study was to retrospectively compare the safety and efficacy of enoxaparin versus unfractionated heparin (UFH) for therapeutic anticoagulation in HD patients.

Materials and Methods

This retrospective chart review evaluated HD patients treated with subcutaneous enoxaparin that were matched based on the indication for anticoagulation with patients treated with intravenous UFH to achieve therapeutic anticoagulation. Primary outcome measures included 30-day incidence of thromboembolic events and major bleeding. Secondary outcomes included rehospitalization within 30 days, length of stay, and mortality.

Results

One hundred sixty-four patients were evaluated, 82 in each group. The average daily dose of enoxaparin used to target therapeutic levels was 0.7 ± 0.2 mg/kg/day (range = 0.4-1). Comparing enoxaparin to UFH, there was no significant difference in major bleeding (6.1% vs 11%, p = 0.4) or thromboembolism (0% vs 2.4%, p = 0.5). Hospital length of stay was shorter in the enoxaparin group (20 ± 53.8 vs 28.9 ± 44.5 days, p = 0.02); there was no significant difference between groups in mortality or readmission. Adjusting for risk factors for bleeding there was a slight but statistically non-significant difference between enoxaparin versus UFH (OR = 0.77, 95%CI: 0.2-3.5, p = 0.73).

Conclusions

These findings suggest that therapeutic dosing of enoxaparin, in doses that ranged from 0.4-1 mg/kg/day, was as safe as intravenous UFH in providing therapeutic anticoagulation in stable patients requiring chronic hemodialysis.     

Increased serum levels of high mobility group box 1 protein in patients with autistic disorder

Background

High mobility group box 1 (HMGB1) is a highly conserved, ubiquitous protein that functions as an activator for inducing the immune response and can be released from neurons after glutamate excitotoxicity. The objective of the present study was to measure serum levels of HMGB1 in patients with autistic disorder and to study their relationship with clinical characteristics.

Methods

We enrolled 22 adult patients with autistic disorder (mean age: 28.1 ± 7.7 years) and 28 age- and gender-matched healthy controls (mean age: 28.7 ± 8.1 years). Serum levels of HMGB1 were measured by enzyme-linked immunosorbent assay (ELISA).

Results

Compared with healthy subjects, serum levels of HMGB1 were significantly higher in patients with autistic disorder (10.8 ± 2.6 ng/mL versus 5.6 ± 2.5 ng/mL, respectively, P < 0.001). After adjustment for potential confounders, serum HMGB1 levels were independently associated with their domain A scores in the Autism Diagnostic Interview-Revised, which reflects their impairments in social interaction.

Conclusions

These results suggest that HMGB1 levels may be affected in autistic disorder. Increased HMGB1 may be a biological correlate of the impaired reciprocal social interactions in this neurodevelopmental disorder.     

Reduced ANXA5 mRNA and protein expression in pregnancies complicated by preeclampsia

Introduction

The placental anticoagulant protein Annexin A5 (ANXA5) is a multifunctional protein that is highly expressed on the apical surfaces of syncytiotrophoblasts, and plays an important role in haemostatic regulations, maintaining blood fluidity of the placenta. The aim of this study was to investigate the expression of ANXA5 in pregnancies complicated by preeclampsia (PE).

Materials and Methods

Placental tissue samples were collected from 23 pregnancies with PE and 34 normal pregnancies. ANXA5 mRNA levels were measured by quantitative Real-Time PCR (qPCR), while ANXA5 protein expression was measured by Western Blot (WB) and immunohistochemistry.

Results

ANXA5 mRNA expression in PE samples was lower than 1% of its expression in normal samples (mean ± SD: 0.002 ± 0.004 vs. 0.55 ± 0.38, p < 0.001), while ANXA5 protein levels in PE samples were approximately at 65% of the average normal expression (mean ± SD: 0.53 ± 0.30 vs. 0.81 ± 0.25, p = 0.001). Immunohistochemical analysis also verified the above results, since PE placentas tended to have low labelling indexes (LIs), in contrast to controls which demonstrated high LIs (p = 0.020). Statistical analysis of the WB data revealed that ANXA5 protein expression was increased in PE smokers vs. PE non-smokers (mean ± SD: 0.64 ± 0.23 vs. 0.41 ± 0.33, p = 0.027).

Conclusions

These results suggest that ANXA5 downregulation could be part of the pathophysiology of PE and the possible impairment in coagulation processes, which are seen in pregnancies that demonstrate PE. Further studies may investigate whether ANXA5 could be used as a biomarker for the early detection of PE and for the prediction of its severity.     

Anti-Xa Activity After Enoxaparin Prophylaxis In Hospitalized Patients Weighing Less Than Fifty-Five Kilograms

Introduction

Low-molecular-weight heparins are commonly used for the prophylaxis of thromboembolic disease. In contrast to therapeutic doses, recommended prophylactic doses are fixed (i.e., 40 mg/day enoxaparin). Dosing of patients with extreme body weights has not been well studied, especially dosing of low weight patients.

Objectives

To establish the anti-Xa activity that results from 40 mg/day enoxaparin in inpatients with body weight ≤ 55 kg.

Patients/Methods

Cross-sectional study including inpatients older than 18 years, with body weight ≤ 55 kg, and whose treating physician found indication for 40 mg/day enoxaparin. We excluded patients with renal failure and those using oral anticoagulants. Anti-Xa activity was measured 3 hours after the second dose of enoxaparin. Statistical analyses were conducted to determine the effect of body weight on anti-Xa levels.

Results

Average age was 72.5 years (interquartile range, 30) and median body weight was 49.7 kg (interquartile range, 7). Twenty-five percent of patients weighed ≤ 45 kg, 37.5% weighed 46–50 kg, and 37.5% weighed 51–55 kg. The mean anti-Xa activity was 0.54 ± 0.18 IU/ml, and 60% of the patients exhibited activity ≥ 0.5 IU/ml. Weight and anti-Xa activity inversely correlated (Spearman’s rho = − 0.428, p = 0.001). Patients weighing ≤ 45 kg exhibited higher anti-Xa activity (0.61 ± 0.18 IU/ml, p = 0.008) than heavier patients and an odds ratio of 8 for anti-Xa level ≥ 0.5 IU/ml (95% CI: 1.42-45.06).

Conclusions

Anti-factor Xa activity rises significantly when body weight decreases. Patients of low weight, especially those weighing < 45 kg, exhibited an anti-Xa activity higher than the desired range for thromboembolic prophylaxis.     

Level of agreement between laboratory and point-of-care prothrombin time before and after cardiopulmonary bypass in cardiac surgery

Background

Hemostasis monitoring in cardiac surgery could benefit from an easy to use and fast point-of-care coagulation monitor, since routine laboratory tests have a delay of 30–45 minutes. This study investigated the level of agreement between the point-of-care prothrombin time (PT) with central laboratory PT before and after cardiopulmonary bypass.

Methods

Bland Altman and error grid analysis were used to analyze the agreement between the point-of-care Coaguchek XS Pro device (POC-PT) and the central laboratory prothrombin time (LAB-PT) before cardiopulmonary bypass (CPB) and 3 minutes after protamine administration. Prothrombin times were expressed in international normalized ratios (INR).

Results

The average POC-PT and LAB-PT values of 73 patients were 1.06 ± 0.14 and 1.09 ± 0.13 (P = 0.10) before CPB. POC-PT measurements before CPB showed a good agreement with the LAB-PT, with a bias of − 0.02 ± 0.07 INR and 94% of the values being represented in the clinical acceptable zone of error grid analysis. The mean POC-PT 3 minutes after protamine administration was significantly lower than the LAB-PT (1.35 ± 0.12 vs. 1.70 ± 0.18; P < 0.001). The PT at 3 minutes after protamine administration showed a bias of 0.36 ± 0.14, and 82% of the values were located outside of the clinical acceptable zone in the error grid analysis.

Conclusions

Point-of-care prothrombin time testing was in concordance with conventional laboratory PT prior to cardiopulmonary bypass. At 3 minutes following protamine administration, PT values of the point-of-care device were structurally lower than the laboratory PT values, leading to a disagreement between both tests at that time point.     

Development of a new laboratory test to evaluate antithrombin resistance in plasma

Introduction

We recently reported a variant prothrombin (p.Arg596Leu: prothrombin Yukuhashi) that confers antithrombin resistance to patients with hereditary thrombosis. To detect antithrombin resistance in plasma, we devised a laboratory test analyzing the kinetics of thrombin inactivation using antithrombin.

Materials and Methods

After incubation with prothrombin activator components (phospholipids, CaCl₂, and snake venom), samples were treated with excess antithrombin in the presence or absence of heparin for various time periods. Subsequently, H-D-Phe-Pip-Arg-p-nitoranilide was added and changes in absorbance/min (ΔA/min) were measured at 405 nm.

Results

After 1 min inactivation using antithrombin and heparin, the relative residual thrombin activity of recombinant mutant prothrombin (34.3% ± 2.2%) was higher than that of the wild-type (6.3% ± 1.2 %). After 30 min without heparin, the relative residual thrombin activity of recombinant mutant prothrombin (95.8% ± 0.4%) was higher than that of the wild-type (10.1% ± 1.7%), indicating that this assay could detect antithrombin resistance of the variant 596Leu prothrombin. Moreover, warfarinized plasmas from 2 heterozygous patients with prothrombin Yukuhashi mutation clearly showed higher values of the relative residual thrombin activity than those from 5 thrombosis patients lacking the mutation in the presence or absence of heparin.

Conclusions

We have devised a laboratory test to detect antithrombin resistance in plasma by analyzing the kinetics of thrombin inactivation using antithrombin. This assay may be useful for detecting antithrombin resistance in plasma, even in warfarinized patients.     

Ginkgo biloba for Attention-Deficit/Hyperactivity Disorder in children and adolescents: A double blind,randomized controlled trial

Background

Although stimulants are highly effective in controlling the symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD), some children will not respond to, or are intolerant of stimulants. Thus, the desire for safe and effective nonstimulant medications has risen during the past several years. Ginkgo biloba has been suggested in the treatment of dementia and memory impairment. We hypothesized that G.biloba would be beneficial for treatment of ADHD, and this could be evaluated in a double blind, randomized, parallel group comparison of G.biloba (Ginko T.D.™ Tolidaru, Iran) and methylphenidate.

Methods

Fifty outpatients (39 boys and 11 girls) with a DSM-IV-TR diagnosis of ADHD were study population of this trial. Subjects were recruited from an outpatient child and adolescent clinic for a 6 week double blind, randomized clinical trial. All study subjects were randomly assigned to receive treatment using tablet of Ginko T.D.™ at a dose of 80–120 mg/day depending on weight (80 mg/day for < 30 kg and 120 mg/day for > 30 kg) (group 1) or methylphenidate at a dose of 20–30 mg/day depending on weight (20 mg/day for < 30 kg and 30 mg/day for > 30 kg (group 2) for a 6 week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent ADHD Rating Scale- IV. Patients were assessed at baseline and at 21 and 42 days after the medication started.

Results

Significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores. The changes at the endpoint compared to baseline were: − 6.52 ± 11.43 (mean ± S.D.) and − 15.92 ± 11.44 (mean ± S.D.) for Ginko T.D.™ and methyphenidate, respectively for Parent ADHD Rating Scale. The changes at the endpoint compared to baseline were: − 0.84 ± 6.79 (mean ± S.D.) and − 14.04 ± 8.67 (mean ± S.D.) for Ginko T.D.™ and methyphenidate, respectively for Teacher ADHD Rating Scale.The difference between the Ginko T.D.™ and methylphenidate groups in the frequency of side effects was not significant except for decreased appetite, headache and insomnia that were observed more frequently in the methylphenidate group.

Conclusion

The results of this study suggest that administration of G.biloba was less effective than methylphenidate in the treatment of ADHD.     

Human platelets do not express tissue factor

Background

The controversy about the expression of tissue factor (TF) in platelet after de novo synthesis prevail despite many groups recognize that platelet isolation, assays and reagents, particularly non-specific antibodies, may account for the diversity. In this study the potential of TF expression was evaluated using immune-purified human platelets and employing a very sensitive and highly specific TF activity assay.

Methods

Isolated platelets in plasma anti-coagulated with Fragmin were subjected to stimulation by LPS plus PMA, IgG antibody or TRAP and tested for TF activity.

Results

Platelets stimulated with LPS plus PMA for 4 hours expressed trace amounts of TF like activity (PCA), not inhibited by anti-TF antibody (0.2 ± 0.1 mU/ml blood). Platelets, not immune-adsorbed to remove monocytes, showed significant TF activity (2.0 ± 0.9 mU/ml blood) that was nearly abolished by anti-TF antibody. IgG antibody from patient with lupus anticoagulant failed to enhance the trace amount of PCA as compared to the control in contrast to high TF activity induced in monocytes (0.4 ± 0.1 mU/ml blood versus 27.5 ± 10.5 mU/10⁶ cells) showing that activation of complement is not mediating TF expression. Platelet subjected to TRAP activation for 10 min possessed only trace amounts of PCA that was not inhibited by anti-TF antibody and slightly enhanced by anti-TFPI antibody.

Conclusions

It is concluded that platelets free of monocytes do not express TF activity when stimulated by LPS or activated complement factors, implying no role for Toll like receptor (TLR4) as suggested recently. There is no evidence of TF activity associated with platelets as a result of rapid and dynamic process.     

Inefficient exercise gas exchange identifies pulmonary hypertension in chronic thromboembolic obstruction following pulmonary embolism

Introduction

Persistent obstruction in the pulmonary artery following acute pulmonary embolism (PE) can give rise to both chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic disease without PH (CTED). We hypothesised that cardiopulmonary exercise testing (CPET) may be able to differentiate patients with CTEPH and CTED following unresolved PE which may help guide patient assessment.

Materials and Methods

Fifteen patients with CTEPH and 15 with CTED all diagnosed after PE underwent CT pulmonary angiography, CPET and resting right heart catheterisation. Exercise variables were compared between patients with CTEPH, CTED and 10 sedentary controls and analysed as predictors of a CTEPH diagnosis. Proximal thrombotic burden in CTEPH and CTED was quantified using CT criteria.

Results

Physiological dead space (Vd/Vt) (34.5 ± 11.4 vs 50.8 ± 6.6 %, p < 0.001) and alveolar-arterial oxygen gradient (29 ± 16 vs 46 ± 12 mmHg, p < 0.001) at peak exercise strongly differentiated CTED and CTEPH groups respectively. Resting ventilatory efficiency also differed from control subjects. In both univariate and multivariate analyses, peak exercise Vd/Vt predicted a diagnosis of CTEPH (ROC AUC > 0.88, 0.67 - 0.97) despite a similar degree of proximal thrombotic obstruction to the CTED group (67.5, 55 - 70% and 72.5, 60 - 80% respectively, p = 0.08).

Conclusions

Gas exchange at peak exercise differentiates CTED and CTEPH after PE that can present with no apparent relation to the degree of proximal thrombotic burden. A potential role for CPET exists in guiding further clinical investigations in this setting.     

The coagulation profile of preterm delivery

Introduction

Hypercoagulation was suggested to be involved in preterm birth etiology; however, the coagulation state of preterm parturients remains unelucidated. The study aim was to evaluate the haemostatic system of pregnant women with premature uterine contractions (PUC).

Materials and Methods

The cohort study population consisted of 76 healthy pregnant women admitted with regular PUC. The study group included 38 women who experienced preterm birth; 14 of them had preterm premature rupture of membranes (PPROM). The control group included 38 women who eventually had term delivery. Groups were matched for maternal age, number of births and gestational age at admission. Blood samples were tested for haemostatic parameters and coagulation activation markers.

Results

Significantly shorter PT and aPTT were documented in the study compared to control group (25.7 ± 2 vs. 27.4 ± 2.7 seconds, P = 0.003, and 9.96 ± 0.5 vs. 10.1 ± 0.4 seconds, P = 0.05, respectively), although differences in absolute values were small. There was no significant difference between the two groups in levels of: fibrinogen, D-dimer, protein C-global, free protein S antigen, factor VIII activity, Von Willebrand factor, plasminogen activator inhibitor-1, prothrombin fragments F1 + 2 (PT F1 + 2), tissue factor and tissue factor pathway inhibitor.Women with PPROM had significantly lower PT F1 + 2 levels compared to those who had preterm delivery with intact membranes (351 ± 99 vs. 561 ± 242 pmol/L, P = 0.003).

Conclusions

Shortened PT and aPTT, reflecting increased thrombotic activity in maternal plasma, could serve as a marker of real preterm labor in women with premature uterine contractions. Further prospective studies in a larger cohort are warranted to validate these findings.