scholarly journals Is Generalized and Segmental Dystonia Accompanied by Impairments in the Dopaminergic System?

2021 ◽  
Vol 12 ◽  
Author(s):  
Jun Ikezawa ◽  
Fusako Yokochi ◽  
Ryoichi Okiyama ◽  
Satoko Kumada ◽  
Maya Tojima ◽  
...  
Keyword(s):  
Dopaminergic System ◽  
Rating Scale ◽  
Pathological Examination ◽  
Emission Computed Tomography ◽  
Healthy Controls ◽  
Imaging Data ◽  
Segmental Dystonia ◽  
Significant Difference ◽  
Dat Spect ◽  
The Mean

Background: The pathogenesis of dystonia is remarkably diverse. Some types of dystonia, such as DYT5 (DYT-GCH1) and tardive dystonia, are related to dysfunction of the dopaminergic system. Furthermore, on pathological examination, cell loss in the substantia nigra (SN) of patients with dystonia has been reported, suggesting that impaired dopamine production may be involved in DYT5 and in other types of dystonia.Objectives: To investigate functional dopaminergic impairments, we compared patients with dystonia and those with Parkinson's disease (PD) with normal controls using neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and dopamine transporter single photon emission computed tomography (DAT SPECT).Methods: A total of 18, 18, and 27 patients with generalized or segmental dystonia, patients with PD, and healthy controls, respectively, were examined using NM-MRI. The mean area corresponding to NM in the SN (NM-SN) was blindly quantified. DAT SPECT was performed on 17 and eight patients with dystonia and PD, respectively. The imaging data of DAT SPECT were harmonized with the Japanese database using striatum phantom calibration. These imaging data were compared between patients with dystonia or PD and controls from the Japanese database in 256 healthy volunteers using the calibrated specific binding ratio (cSBR). The symptoms of dystonia were evaluated using the Fahn–Marsden Dystonia Rating Scale (FMDRS), and the correlation between the results of imaging data and FMDRS was examined.Results: The mean areas corresponding to NM in the SN (NM-SN) were 31 ± 4.2, 28 ± 3.8, and 43 ± 3.8 pixels in patients with dystonia, PD, and in healthy controls, respectively. The mean cSBRs were 5 ± 0.2, 2.8 ± 0.2, 9.2 (predictive) in patients with dystonia, PD, and in healthy controls, respectively. The NM-SN area (r = −0.49, p < 0.05) and the cSBR (r = −0.54, p < 0.05) were inversely correlated with the FMDRS. There was no significant difference between the dystonia and PD groups regarding NM-SN (p = 0.28). In contrast, the cSBR was lower in patients with PD than in those with dystonia (p < 0.5 × 10−6).Conclusions: Impairments of the dopaminergic system may be involved in developing generalized and segmental dystonia. SN abnormalities in patients with dystonia were supposed to be different from degeneration in PD.

scholarly journals Striatal dopamine D2/3 receptors in medication-naïve schizophrenia: an [123I] IBZM SPECT study

2021 ◽  
pp. 1-9
Author(s):  
Kao Chin Chen ◽  
Yen Kuang Yang ◽  
Oliver D. Howes ◽  
I Hui Lee ◽  
Tzung Lieh Yeh ◽  
...  
Keyword(s):  
Single Photon ◽  
Imaging Techniques ◽  
Photon Emission ◽  
Striatal Dopamine ◽  
Dopamine Synthesis ◽  
Emission Computed Tomography ◽  
Healthy Controls ◽  
Recent Onset ◽  
Significant Difference ◽  
The Mean

Abstract Background The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels. Methods We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia. Result The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI −0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = −0.01(binding ratio); 95% CI −0.01 to −0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores. Conclusions Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.

scholarly journals Interleukin-37 as an anti-inflammatory cytokine: does its relation to disease activity suggest its potential role in rheumatoid arthritis therapy?

2021 ◽  
Vol 48 (1) ◽  
Author(s):  
Eman A. Baraka ◽  
Mona G. Balata ◽  
Shereen H. Ahmed ◽  
Afaf F. Khamis ◽  
Enas A. Elattar
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Cross Sectional Study ◽  
Healthy Controls ◽  
Tender Joint ◽  
Cross Sectional ◽  
Reactive Protein ◽  
Significant Difference ◽  
The Mean ◽  
Anti Inflammatory

Abstract Background This study aimed to measure the serum and synovial interleukin (IL)-37 levels in rheumatoid arthritis (RA) patients compared to patients with primary knee osteoarthritis (PKOA) and healthy controls and to detect its relation to RA disease activity. Results This cross-sectional study included 50 RA patients with a mean age of 40.24 ± 8.62 years, 50 patients with PKOA with a mean age of 56.69 ± 4.21, and 40 healthy controls with a mean age of 41.75 ± 7.38 years. The mean serum IL-37 level in the RA patients (382.6 ± 73.97 pg/ml) was statistically significantly (P < 0.001) the highest among the studied groups; however, it showed a non-significant difference between the PKOA patients (70.38 ± 27.49 pg/ml) and the healthy controls (69.97 ± 25.12 pg/ml) (P > 0.94). Both serum and synovial IL-37 levels were significantly positively correlated with disease activity scores (r = 0.92, P< 0.001 and r = 0.85, P < 0.001), tender joint counts (r = 0.83, P < 0.001 and r = 0.82, P < 0.001 ), swollen joint counts (r = 0.72, P < 0.001 and r = 0.60, P < 0.001), visual analog scale (r = 0.82, P < 0.001 and r = 0.82, P < 0.001), erythrocyte sedimentation rate (r = 0.75, P < 0.001 and r = 0.65, P < 0.001), and C-reactive protein (r = 0.93, P < 0.001 and r = 0.79, P < 0.001), respectively. Conclusion Serum and synovial IL-37 were significantly elevated in the RA patients, and they were closely correlated. Being less invasive, the serum IL-37 could be a marker of disease activity and could reflect the effective disease control by drugs. Having an anti-inflammatory effect could not suggest IL-37 as the key player to control inflammation alone, but its combination with other anti-proinflammatory cytokines could be investigated.

Vasoactive Intestinal Polypeptide Evokes Only a Minimal Headache in Healthy Volunteers

Cephalalgia ◽  
2006 ◽  
Vol 26 (8) ◽  
pp. 992-1003 ◽  
Author(s):  
JM Hansen ◽  
J Sitarz ◽  
S Birk ◽  
AM Rahmann ◽  
PS Oturai ◽  
...  
Keyword(s):  
Vasoactive Intestinal Polypeptide ◽  
Healthy Subjects ◽  
Rating Scale ◽  
Superficial Temporal Artery ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Mean Flow ◽  
Arterial Blood ◽  
Significant Difference ◽  
Intestinal Polypeptide

The role of the parasympathetic nervous system in the pathogenesis of migraine is disputed. The headache-eliciting effect of the parasympathetic neurotransmitter, vasoactive intestinal polypeptide (VIP), and its effect on cerebral arteries and brain haemodynamics has not been systematically studied in man. We hypothesized that infusion of VIP might induce headache in healthy subjects and cause changes in cerebral haemodynamics. VIP (8 pmol/kg per min) or placebo (0.9± saline) was infused for 25 min into 12 healthy young volunteers in a crossover, double-blind design. Headache was scored on a verbal rating scale from 0 to 10, regional cerebral blood flow (rCBF) was measured with single-photon emission computed tomography and 133Xe inhalation and mean flow velocity in the middle cerebral artery (VmeanMCA) was measured with transcranial Doppler ultrasonography. The headache was very mild with a maximum score of 2 and described as a pressing or throbbing sensation. Five participants developed headache during VIP and one during placebo. During the infusion, a significant drop in VmeanMCA was seen for VIP compared with placebo ( P < 0.001), but the effect quickly waned and no difference was found when comparing the time between 30 and 120 min. In addition, no significant difference in the diameter of the MCA could be found during the infusion. No significant differences in rCBF ( P = 0.10) were found between VIP and placebo. A marked dilation of the superficial temporal artery was seen ( P = 0.04) after VIP in the first 30 min but no difference was found when comparing the time between 30 and 120 min. We found no difference in mean arterial blood pressure between VIP and placebo days but the heart rate increased significantly on a VIP day compared with a placebo day (AUC0–30min, P < 0.001). Plasma VIP was significantly higher on a VIP day compared with placebo (AUC0–80min, P < 0.001). These results show that VIP causes a decrease in VmeanMCA without affecting rCBF. In spite of a marked vasodilator effect in the extracranial vessels and increased plasma VIP, healthy subjects developed only a very mild headache.

A Controlled Comparative Trial of a New Antidepressant, Ciclazindol

1979 ◽  
Vol 7 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Sidney Levine
Keyword(s):  
Rating Scale ◽  
Comparative Trial ◽  
Poor Response ◽  
Endogenous Depression ◽  
Depressive Illness ◽  
Double Blind ◽  
Significant Difference ◽  
Severity Of Depression ◽  
The Mean ◽  
Rate Of Response

The author describes a controlled, double-blind, comparative trial of a new tetracyclic compound, ciclazindol (WY 23409), against amitriptyline in the treatment of thirty-five patients admitted to hospital with depressive illness. Each patient was randomly allocated to three weeks treatment with either 50 mg b.d. ciclazindol or 50 mg b.d. amitriptyline. In the event of a poor response the dose level was raised to 75 mg b.d. Separation of cases of endogenous depression and severity of depression were assessed by the Levine-Pilowsky Depression Questionnaire, a self-rating technique. Severity of depression was also assessed using the Hamilton Rating Scale. No significant difference was noted between the drugs in either the degree or the rate of response nor when the endogenous cases alone were studied. The interesting observation was made that only one-third of ciclazindol patients gained weight compared to almost three-quarters of the amitriptyline group and the mean weight gain of the latter was over double that of the ciclazindol group. The author concludes that ciclazindol offers promise and merits further study using higher dosage levels once its full safety trials have been completed.

Effect of migraine attack on pupil size, accommodation and ocular aberrations

2020 ◽  
pp. 112067212097533
Author(s):  
Merve Beyza Yildiz ◽  
Elvin Yildiz ◽  
Sevcan Balci ◽  
Buse Rahime Hasirci Bayir ◽  
Yılmaz Çetinkaya
Keyword(s):  
Migraine Attack ◽  
Pupil Size ◽  
Case Control Study ◽  
Case Control ◽  
Healthy Controls ◽  
Unilateral Headache ◽  
Significant Difference ◽  
The Mean ◽  
Control Study ◽  
Prospective Case Control Study

Purpose: To evaluate the pupil size, accommodation, and ocular higher-order aberrations (HOAs) in patients with migraine during migraine attacks and compare them with interictal period and healthy controls. Methods: This prospective, case–control study included 48 eyes of 24 patients with migraine and 48 eyes of 24 age and sex-matched healthy controls. Measurements were performed using a Hartmann Shack aberrometer. Accommodative responses to accommodative stimulus ranging from 0 to 5 diopters (D) in increments of 0.5 D were recorded. Spherical, coma, trefoil aberration, and root mean square (RMS) of total HOAs were assessed. Patients with migraine were measured twice during the interictal phase and during migraine attack. Results: The mean pupil size significantly decreased during migraine attack (5.85 ± 0.19 mm) compared with the interictal phase (6.05 ± 0.19 mm) in the patients with migraine ( p = 0.012). There was a significant increase in the accommodative response to accommodative stimulus of 1.5 to 5 D during migraine attack. No significant change was observed in HOAs during migraine attack. In addition, no ictal or interictal period measurements were statistically significantly different from the controls. Comparing symptomatic and non-symptomatic sides in 17 migraine patients with unilateral headache, no significant difference was found in any of the measurements in both ictal and interictal periods. Conclusion: Our results suggest the presence of a subtle oculosympathetic hypofunction in patients with migraine during the ictal period compared to the interictal period. The accommodation status of the eye seems to be affected by this autonomic dysfunction.

scholarly journals Sputum and plasma adiponectin levels in clinically stable adult cystic fibrosis patients with CFTR I1234V mutation

2019 ◽  
Author(s):  
Atqah AbdulWahab ◽  
Mona Allangawi ◽  
Merlin Thomas ◽  
Ilham Bettahi ◽  
Siveen K. Sivaraman ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Adiponectin Level ◽  
Pancreatic Insufficiency ◽  
Forced Expiratory Volume ◽  
Healthy Controls ◽  
Cross Sectional ◽  
Plasma Adiponectin ◽  
Inflammatory Status ◽  
Significant Difference ◽  
The Mean

Abstract Background: Cystic fibrosis (CF) lung disease is associated with chronic inflammation leading to progress in lung function. Adiponectin is a predominantly anti-inflammatory adipokine that may have a role in CF lung. This study aims to determine total sputum and total plasma adiponectin levels in clinically stable adults CF patients with CFTR I1234V mutation, compared to plasma adiponectin levels in healthy controls and to investigate their correlations with body mass index (BMI) and spirometry in patients with CF. Methods: A cross-sectional study comprises 17 CF patients and 18 healthy controls. Adiponectin levels were measured by magnetic bead-based multiplex assay. Results: The mean age of adult CF patients was 22.9 years± 3.8 (18-30) and 76.5% CF patients had pancreatic sufficiency. The mean BMI in healthy controls was slightly higher than CF patients. The mean sputum adiponectin level was significantly lower than plasma adiponectin levels in CF patients and healthy controls (p<0.001), whereas no significant difference in plasma adiponectin levels between CF patients and healthy controls. The mean sputum adiponectin level was observed to be higher in CF patients with pancreatic insufficiency. Sputum adiponectin level was correlated positively with plasma adiponectin level in CF patients (r= 0.47, p=0.06). Sputum and plasma adiponectin levels in CF patients were correlated negatively with BMI and percentage predicted forced expiratory volume in 1 second (FEV1) and Forced vital capacity (FVC). Conclusions: Sputum adiponectin may provide a minimally invasive tool in the assessment of an inflammatory status in CF patients. Further larger study to address any difference in sputum and plasma adiponectin levels among CF patients with pancreatic sufficiency versus pancreatic insufficiency.

scholarly journals The Diagnostic Value of SPECT/CT in Predicting the Occurrence of Osteonecrosis following Femoral Neck Fracture : a prospective cohort study

2020 ◽  
Author(s):  
Jae Youn Yoon ◽  
Soong Joon Lee ◽  
Kang Sup Yoon ◽  
Pil Whan Yoon
Keyword(s):  
Computed Tomography ◽  
Femoral Head ◽  
Femoral Neck ◽  
Femoral Neck Fracture ◽  
Diagnostic Value ◽  
Emission Computed Tomography ◽  
Uptake Ratio ◽  
Significant Difference ◽  
Neck Fracture ◽  
The Mean

Abstract Backgrounds One of the most significant complications after a femoral neck fracture is osteonecrosis of the femoral head (ONFH). The concomitant use of single-photon emission computed tomography (SPECT) with computed tomography (CT) increases the sensitivity for detecting the anatomic location and severity of ONFH. In this study, we evaluated the diagnostic value of SPECT/CT for the occurrence of ONFH by quantifying the perfusion status of the femoral head. Methods A total of 30 patients who had multiple pinnings for femur neck fractures were included in this study. We classified the perfusion status into three groups: normal perfusion, decreased perfusion, and avascular groups, and compared the occurrence of femoral head necrosis between them. For quantitative analysis, we evaluated the uptake ratio of both femur heads (head-to-head uptake ratio). If the patient’s contralateral hip was incomparable, we measured the uptake ratio from the superior dome of the ipsilateral acetabulum (head-to-acetabulum uptake ratio). Results Twenty-four patients out of 30 achieved bone union, whereas the others developed ONFH. When the population was divided into intact and defective perfusion groups on scintigraphy, the sensitivity, specificity, and accuracy of the test were 83.3%, 75.0%, and 76.7%, respectively. The mean head-to-head uptake ratio value with a 95% confidence interval (CI) was 1.10 (95% CI: 0.85 – 1.36). In the osteonecrosis group, the mean value of the head-to-head uptake ratio was 0.33 (95% CI: 0.28 – 0.38). In contrast, the ratio was 1.30 (95% CI: 1.03 – 1.57) in the non-osteonecrosis group, demonstrating a significant difference in the uptake ratio ( P < 0.001). When the cutoff value of the uptake ratio was set to 0.5, both the sensitivity and specificity were 100%. There was also a significant difference in the head-to-acetabulum uptake ratio between the two groups ( P < 0.001). Conclusions SPECT/CT was useful in evaluating the perfusion status of the femoral head, showing high accuracy in predicting the occurrence of avascular necrosis. To demonstrate the reliability and validity of SPECT/CT, further prospective studies on a larger scale are warranted.

scholarly journals Pengaruh Hypnosis Terhadap Tingkat Kecemasan Ibu Hamil Nullipara Triwulan III Dalam Persiapan Menghadapi Persalinan

2016 ◽  
Vol 2 (1) ◽  
pp. 24-32
Author(s):  
Sugeng Triyani ◽  
Fatimah Fatimah ◽  
Aisyah Aisyah
Keyword(s):  
Pregnant Women ◽  
Rating Scale ◽  
Comparison Group ◽  
P Value ◽  
Group Design ◽  
Nulliparous Women ◽  
Significant Difference ◽  
Experiment Method ◽  
Hamilton Anxiety Rating Scale ◽  
The Mean

Adaptability of pregnant women toward labor preparation is very important. If the mother cannot adapt during the process of labor, usually she will experience anxiety and will give a response of fight or flight triggered by the abundance of Catecholamines hormones and by the presence of fear and other forms of distress. This research used a quasi experiment method with  non  randomized pretest potest  equivalent group  design,  without intervention on  the comparison group. The quetionnaire of Hamilton Anxiety Rating Scale was used to measure the level of anxiety among pregnant women given hypnosis therapy with pregnant women not given the hypnosis therapy. The results showed that there was a significant difference in the mean level of anxiety between cases and controls (SD of 6,004). There was a significant influence on the group that used hypnosis therapy with a mean decrease in anxiety by 21.550 poin with a p value of < 0.001. Therefore, hypnosis is effective in reducing anxiety among nulliparous women in the third quarter of pregnancy.

scholarly journals The Diagnostic Value of SPECT/CT in Predicting the Occurrence of Osteonecrosis Following Femoral Neck Fracture: a Prospective Cohort Study

2020 ◽  
Author(s):  
Jae Youn Yoon ◽  
Soong Joon Lee ◽  
Kang Sup Yoon ◽  
Pil Whan Yoon
Keyword(s):  
Computed Tomography ◽  
Femoral Head ◽  
Femoral Neck ◽  
Femoral Neck Fracture ◽  
Diagnostic Value ◽  
Emission Computed Tomography ◽  
Uptake Ratio ◽  
Significant Difference ◽  
Neck Fracture ◽  
The Mean

Abstract BackgroundsOne of the most significant complications after a femoral neck fracture is osteonecrosis of the femoral head (ONFH). The concomitant use of single-photon emission computed tomography (SPECT) with computed tomography (CT) increases the sensitivity for detecting the anatomic location and severity of ONFH. In this study, we evaluated the diagnostic value of SPECT/CT for the occurrence of ONFH by quantifying the perfusion status of the femoral head.MethodsA total of 30 patients who had multiple pinnings for femur neck fractures were included in this study. We classified the perfusion status into three groups: normal perfusion, decreased perfusion, and avascular groups, and compared the occurrence of femoral head necrosis between them. For quantitative analysis, we evaluated the uptake ratio of both femur heads (head-to-head uptake ratio). If the patient’s contralateral hip was incomparable, we measured the uptake ratio from the superior dome of the ipsilateral acetabulum (head-to-acetabulum uptake ratio).ResultsTwenty-four patients out of 30 achieved bone union, whereas the others developed ONFH. When the population was divided into intact and defective perfusion groups on scintigraphy, the sensitivity, specificity, and accuracy of the test were 83.3%, 75.0%, and 76.7%, respectively. The mean head-to-head uptake ratio value with a 95% confidence interval (CI) was 1.10 (95% CI: 0.85–1.36). In the osteonecrosis group, the mean value of the head-to-head uptake ratio was 0.33 (95% CI: 0.28–0.38). In contrast, the ratio was 1.30 (95% CI: 1.03–1.57) in the non-osteonecrosis group, demonstrating a significant difference in the uptake ratio (P < 0.001). When the cutoff value of the uptake ratio was set to 0.5, both the sensitivity and specificity were 100%. There was also a significant difference in the head-to-acetabulum uptake ratio between the two groups (P < 0.001).ConclusionsSPECT/CT was useful in evaluating the perfusion status of the femoral head, showing high accuracy in predicting the occurrence of avascular necrosis. To demonstrate the reliability and validity of SPECT/CT, further prospective studies on a larger scale are warranted.

Common VWF Haplotypes in Normal African-Americans and Caucasians Recruited into the ZPMCB-VWD and Their Impact on VWF Laboratory Testing.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 714-714
Author(s):  
Veronica H. Flood ◽  
B.C. Kautza ◽  
C.A. Miller ◽  
B.R. Branchford ◽  
J.C. Gill ◽  
...  
Keyword(s):  
African American ◽  
African Americans ◽  
Gene Sequencing ◽  
Von Willebrand Disease ◽  
Control Group ◽  
Healthy Controls ◽  
Significant Difference ◽  
The Mean ◽  
Bleeding Score ◽  
Von Willebrand

Abstract Von Willebrand disease (VWD) is a common bleeding disorder that has been reported to affect up to 1% of the population. Diagnostic testing for VWD relies on specific tests of von Willebrand factor (VWF) that include VWF antigen (Ag) and VWF ristocetin cofactor activity (RCo). Variability in these tests, especially in the RCo, has the potential to affect diagnosis of VWD. Clinically, the RCo/Ag ratio is used to identify patients with type 2M VWD, of which 35% of our local type 2M index cases were of African-American descent. As part of the ZPMCB-VWD, a large study of both healthy controls and patients with VWD, we evaluated VWF Ag, RCo, multimers, EU bleeding score, and VWF gene sequencing to look for mutations and/or common polymorphisms (SNPs) that might contribute to RCo measurement. Healthy controls completed a computerized version of the EU bleeding score and provided blood for clinical VWF testing. Since platelet VWF binding primarily involves the A1 domain of VWF, exon 28 gene sequencing was analyzed and common SNPs were identified, particularly in African-Americans (AA) with altered RCo/Ag ratios. Statistical comparisons were performed using t-tests. For the AA control group, the presence of specific exon 28 SNPs, including I1380V, N1435S, and D1472H, correlated with a low RCo/Ag. In controls, the 3 SNPs occurred together in 22% of AA and 1.5% of Caucasians. For AA controls with all 3 SNPs, the mean Ag was 155, RCo 115, and RCo/Ag 0.77, while for AA without the 3 SNPs, the mean Ag was 129, RCo 129, and RCo/Ag 1.01. The difference in RCo/Ag ratio was significant (p<0.001). In comparison, the Caucasian controls without the 3 SNPs had a mean Ag of 108, RCo of 115, and RCo/Ag of 1.08. When only D1472H was considered, a significant difference in RCo/Ag ratio was noted for both African-American and Caucasian controls with D1472H (present in 63% of AA and 24% of Caucasian controls). For AA controls with D1472H, the mean RCo/Ag ratio was 0.82 (range 0.42–1.16) compared to 1.01 for those without the SNP (p<0.001). The Caucasian controls with D1472H had a mean ratio of 0.87 (range 0.57–1.17) compared to 1.08 for those without the SNP (p<0.001). EU Bleeding Score was not significantly affected by either race or SNP status. All Caucasian controls with D1472H were heterozygous, while 14% of the African-American controls were homozygous. The mean RCo/Ag for the homozygous controls was 0.71, compared to 0.86 for the AA heterozygous controls (p<0.025). In order to determine if the exon 28 SNPs intrinsically altered the measurement of VWF, the 3 SNPs were engineered into recombinant VWF and expressed in HEK293T cells. VWF Ag and RCo were performed on the purified expressed VWF. The RCo/Ag ratios for the recombinant expressed VWF were decreased for 1380V and 1472H, while the construct containing all 3 SNPs showed an even lower ratio (59% of wild-type RCo/Ag ratio). These data suggest that specific exon 28 SNPs may contribute to low RCo/Ag ratios, especially in the African-American population. Since the RCo assay involves ristocetin binding to VWF, mutations (and polymorphisms) in VWF may affect the measurement of “VWF activity” by this assay and might not reflect true hemorrhagic risk.

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