Thrombin generation in severe haemophilia A and B: the endogenous thrombin potential in platelet-rich plasma

Thrombin generation was investigated in platelet-rich plasma (PRP) from 11 healthy controls, 17 patients with severe haemophilia A and 7 patients with severe haemophilia B. Mean endogenous thrombin potential (ETP) in arbitrary fluorescence units (FU) was 226.9 +/- 44.6, 186.4 +/- 22.5, 154.2 +/- 41.3 in controls, haemophilia A and B, respectively, all at a platelet count of 200 x 10(9)/l (p = 0.004 for controls vs. haemophilia A, p = 0.003 for controls vs. haemophilia B, no significant difference between haemophilia A and B). The contribution of FVIII to thrombin generation in haemophilia A was 1.31 +/- 0.16 FU/% of FVIII:C activity, while for FIX in haemophilia B this was 0.80 +/- 0.21 FU/% of FIX activity. There was an almost linear relationship between increasing platelet count and thrombin generation up to a mean platelet count of 100 x 10(9)/l. Further increase in platelet count has only a marginal influence on thrombin generation. Platelets increase ETP in haemophilia A by 0.184 +/- 0.022 FU/10(9) platelets/l and in haemophilia B by 0.319 +/- 0.085 FU/10(9) platelets/l, and this was significantly different between the two groups (p = 0.0002). This influence of plate-lets diminishes with increasing concentration of either FVIII or FIX. In conclusion, there is a difference in thrombin generation between haemophilia A and B, and this may be attributed to the role of platelets in the assembly of the tenase complex on their surface.     

Type 1 diabetes patients born to immigrants to Sweden increase their native diabetes risk and differ from Swedish patients in HLA types and islet autoantibodies

Delli AJ, Lindblad B, Carlsson A, Forsander G, Ivarsson S‐A, Ludvigsson J, Marcus C, Lernmark Å; for the Better Diabetes Diagnosis (BDD) Study Group. Type 1 diabetes patients born to immigrants to Sweden increase their native diabetes risk and differ from Swedish patients in HLA types and islet autoantibodies. Aim: To determine whether type 1 diabetes mellitus (T1DM) patients, having parents who immigrated to Sweden, have increased T1DM risk before 18 yr compared with countries of origin. We also determined whether they have different human leukocyte antigen (HLA) genetic markers and islet autoantibodies at diagnosis compared with Swedish patients. Methods: A total of 1988 (53% males) newly diagnosed and confirmed T1DM patients <18 yr registered within the Better Diabetes Diagnosis (BDD) study (May 2005 to September 2008) were included. Participants were classified into three groups: Swedish, non‐Swedish, and Mixed‐origin patients according to country of origin of two generations (parents and grandparents). These groups were compared with respect to T1DM HLA markers and islet autoantibodies [glutamic acid decarboxylase autoantibodies (GAD65Ab), insulin autoantibodies (IAA), and islet antigen‐2 autoantibodies (IA‐2Ab)]. Results: Only 30 (1.5%) patients were born outside Sweden. Swedish patients constituted 66%, non‐Swedish patients 8%, Mixed origins 17%, and 9% were of uncertain origin. Confirmed T1DM in patients within the study was 22 (95% CI: 21–23) patients/10⁵/yr rate for Swedish patients compared with 14 (95% CI: 13–15) among non‐Swedish patients. The HLA‐DQ8 haplotype (p < 0.0001) and DQ2/8 genotype (p < 0.02) predominated among Swedish compared with non‐Swedish patients. In contrast, DQ2 was the most frequent haplotype among non‐Swedish patients [OR = 1.5 (95% CI: 1.0–2.0), p < 0.04]. Multiple (≥2) autoantibodies (p < 0.04) and specifically IA‐2Ab (p < 0.001) were most prevalent among the Swedish patients. Multiple autoantibodies were associated with DQ8 among the Swedish patients only (p < 0.001). Conclusion: Patients born to parents who had immigrated to the high T1DM incidence environment of Sweden have, compared with Swedish patients, more frequent HLA‐DQ2 genetic markers and are diagnosed more often with GAD65Ab.     

The Pharmacology of Lysergic Acid Diethylamide: A Review

Lysergic acid diethylamide (LSD) was synthesized in 1938 and its psychoactive effects discovered in 1943. It was used during the 1950s and 1960s as an experimental drug in psychiatric research for producing so‐called “experimental psychosis” by altering neurotransmitter system and in psychotherapeutic procedures (“psycholytic” and “psychedelic” therapy). From the mid 1960s, it became an illegal drug of abuse with widespread use that continues today. With the entry of new methods of research and better study oversight, scientific interest in LSD has resumed for brain research and experimental treatments. Due to the lack of any comprehensive review since the 1950s and the widely dispersed experimental literature, the present review focuses on all aspects of the pharmacology and psychopharmacology of LSD. A thorough search of the experimental literature regarding the pharmacology of LSD was performed and the extracted results are given in this review. (Psycho‐) pharmacological research on LSD was extensive and produced nearly 10,000 scientific papers. The pharmacology of LSD is complex and its mechanisms of action are still not completely understood. LSD is physiologically well tolerated and psychological reactions can be controlled in a medically supervised setting, but complications may easily result from uncontrolled use by layman. Actually there is new interest in LSD as an experimental tool for elucidating neural mechanisms of (states of) consciousness and there are recently discovered treatment options with LSD in cluster headache and with the terminally ill.     

Lower Placebo Responses After Long-Term Exposure to Fibromyalgia Pain

Knowledge about placebo mechanisms in patients with chronic pain is scarce. Fibromyalgia syndrome (FM) is associated with dysfunctions of central pain inhibition, and because placebo analgesia entails activation of endogenous pain inhibition, we hypothesized that long-term exposure to FM pain would negatively affect placebo responses. In our study we examined the placebo group (n = 37, mean age 45 years) from a 12-week, randomized, double-blind, placebo-controlled trial investigating the effects of milnacipran or placebo. Twenty-two patients were classified as placebo nonresponders and 15 as responders, according to the Patient Global Impression of Change scale. Primary outcome was the change in pressure pain sensitivity from baseline to post-treatment. Secondary outcomes included ratings of clinical pain (visual analog scale), FM effect (Fibromyalgia Impact Questionnaire), and pain drawing. Among placebo responders, longer FM duration was associated with smaller reductions in pressure pain sensitivity (r = .689, P = .004), but not among nonresponders (r = ?.348, P = .112). In our study we showed that FM duration influences endogenous pain regulation, because pain levels and placebo-induced analgesia were negatively affected. Our results point to the importance of early FM interventions, because endogenous pain regulation may still be harnessed at that early time. Also, placebo-controlled trials should take FM duration into consideration when interpreting results.

Self-administered tests as a screening procedure for pregnancy-related pelvic girdle pain

The aim of this study was to investigate sensitivity and specificity of self-administrated tests aimed at pain provocation of posterior and/or anterior pelvis pain and to investigate pain intensity during and after palpation of the symphysis. A total of 175 women participated in the study, 100 pregnant women with and 25 pregnant women without lumbopelvic back pain and 50 non-pregnant women. Standard pain provocation tests were compared with self assessed tests. All women were asked to estimate pain during and after palpation of the symphysis. For posterior pelvic pain, the self-test of P4 and Bridging test had the highest sensitivity of 0.90 versus 0.97 and specificity of 0.92 and 0.87. Highest sensitivity for self-test for anterior pelvic pain was pulling a mat 0.85. Palpation of symphysis was painful and persistency of pain was the longest among women who fulfilled the criteria for symphyseal pain. There were overall significant differences between the groups concerning intensity and persistency of pain (P < 0.001). Our results indicate that pregnant women can perform a screening by provocation of posterior pelvic pain by self-tests with the new P4 self-test and the Bridging test. Palpation of the symphysis is painful and should only be used as a complement to history taking, pain drawing and pulling a MAT-test.     

Posterior pelvic pain provocation test is negative in patients with lumbar herniated discs

The classification of pelvic girdle pain can only be reached after lumbar causes have been excluded by a clinical examination. During clinical examination, the posterior pelvic pain provocation test is a well-established method for verifying pelvic girdle pain. However, a criticism of pelvic pain provocation tests is that they may have an effect on lumbar structures, thus yielding false-positive results. The posterior pelvic pain provocation test was performed with four groups of patients: patients with computed tomography-verified disc herniations (1) on the waiting list for surgery (14 women; 9 men); (2) 6 weeks after disc surgery (18 women, 12 men); (3) pregnant women seeking care for pelvic girdle pain (n = 25); and (4) women with persistent pelvic girdle pain after delivery (n = 32). The sensitivity of the posterior pelvic pain provocation test was 0.88 and the specificity was 0.89. The positive predictive value was 0.89 and the negative predictive value was 0.87. Analysis of only women showed similar results. In our study, the posterior pelvic pain provocation test was negative in patients with a well-defined lumbar diagnosis of lumbar disc herniation, both before and after disc surgery. Our results are an important step toward the more accurate classification of lumbopelvic pain.     

The prevalence of activated protein C (APC) resistance and factor V Leiden is significantly higher in patients with retinal vein occlusion without general risk factors. Case-control study and meta-analysis

Several small case-control studies have investigated whether factor V Leiden (FVL) is a risk factor for retinal vein occlusion (RVO) and generated conflicting data. To clarify this question we performed a large two-centre case-control study and a meta-analysis of published studies. Two hundred seven consecutive patients with RVO and a control group of 150 subjects were screened between 1996 and 2006. A systematic meta-analysis was done combining our study with further 17 published European case-control studies. APC resistance was detected in 16 out of 207 (7.7%) patients and eight out of 150 (5.3%) controls. The odds ratio (OR) estimated was 1.49 with a (non-significant) 95% confidence interval (CI) of 0.62-3.57. The meta-analysis including 18 studies with a total of 1,748 patients and 2,716 controls showed a significantly higher prevalence of FVL in patients with RVO compared to healthy controls (combined OR 1.66; 95% CI 1.19-2.32). All single studies combined in the meta-analysis were too small to reliably detect the effect individually. This explains the seemingly contradictory data in the literature. In conclusion, the prevalence of APC resistance (and FVL) is increased in patients with RVO compared to controls, but the effect is only moderate. Therefore, there is no indication for general screening of factor V mutation in all patients with RVO. We recommend this test to be performed in patients older than 50 years with an additional history of thromboembolic event and in younger patients without general risk factors like hypertension.     

Incidence of biopsy-proven bone tumors in children: a report based on the Dutch pathology registration "PALGA"

INTRODUCTION: Data on childhood bone tumors are mainly confined to reports on malignant tumors or on institutional registries. Incidence figures on both benign and malignant bone tumors in childhood are lacking. METHODS: From January 1999 to December 2003, 1474 newly diagnosed bone tumors in children up to 18 years were registered in Pathologisch Anatomisch Landelijk Geautomatiseerd Archief (the nationwide network and registry of histopathology and cytopathology in The Netherlands). Data provided were diagnosis, date of birth, age at diagnosis, and localization. For incidence calculations, data on age and sex in each year of investigation were obtained from the StatLine database of Statistics Netherlands (www.cbs.nl). RESULTS/CONCLUSIONS: Incidence of pathology-proven bone tumors in children is low. Incidence of pathology-proven bone tumors in The Netherlands is 79.3 per 1,000,000. From the very first year of life, incidence increases from 3.9 per 1,000,000 to a peak at 13 to 15 years of 142.9 per 1,000,000. Osteochondromas are the most prevalent tumors, followed by aneurysmal bone cysts. The overall incidence is higher for male compared with female patients, mainly due to different frequencies found in aneurysmal bone cysts, Ewing sarcoma, and osteochondroma. Shifts in incidence differ among the various tumors. In infants, bone tumors are mainly chondromas and fibrous dysplasia, which both show a steady increase at older ages. Tumors most prevalent at older ages are osteochondromas, osteosarcomas, osteoid osteomas, and chondromas. A peak incidence at approximately the age of 10 is noted for solitary bone cysts, nonossifying fibromas, and osteoblastomas. Small children more often have localizations in the skull and facial bones. Comparison with literature data showed significant differences due to referral-based institutionally bias, whereas tumor registries only give data for specific tumor types.     

The risk injury to the posterior interosseous nerve in standard approaches to the proximal radius: a cadaver study

Purpose  

The aim of this study was to provide guidance on the safe zones for the exposure of the proximal radius by measuring the distance from the PIN to various anatomical landmarks in the proximal forearm in pronation and supination.