Contribution of hyperpolarization-activated channels to heat hypersensitivity and ongoing activity in the neuritis model.

Neuritis can cause pain hypersensitivities in the absence of axonal degeneration. Such hypersensitivities are reputed to be maintained by ongoing activity into the spinal cord, which, in the neuritis model, is mainly generated from intact C-fiber neurons. The hyperpolarization-activated cyclic nucleotide-gated (HCN) family of ion channels has been implicated in nerve injury-induced pain hypersensitivities. The present study has examined the role of these channels in the development of heat and mechanical hypersensitivities in the neuritis model. The systemic administration of the HCN-specific blocker ZD7288 produced a reversal of heat but not mechanical hypersensitivity within one hour post-administration. Recordings from C-fiber neurons were performed to determine whether ZD7288 acts by inhibiting ongoing activity. ZD7288 (0.5mM) caused a 44.1% decrease in the ongoing activity rate following its application to the neuritis site. Immunohistochemical examination of the HCN2 channel subtype within the L5 dorsal root ganglia revealed an increase in expression in neuronal cell bodies of all sizes post-neuritis. In conclusion, HCN channels contribute to the development of neuritis-induced heat hypersensitivity and ongoing activity. Drugs that target HCN channels may be beneficial in the treatment of neuropathic pain in patients with nerve inflammation.

Eosinophilic esophagitis in children with esophageal atresia.

Eosinophilic esophagitis (EoE) has only rarely been reported in esophageal atresia (EA) patients. A retrospective case analysis of all EA patients born at our center between January 1999 and April 2012 was performed. A total of 113 of patients were identified; 10 patients were excluded as a result of inadequate data. Eighteen patients (17%) were diagnosed with EoE. The average number of eosinophilis was 30/high-power field (HPF) (19/HPF-80/HPF). The median age for diagnosis of EoE was 1 year and 6 months (8 months-8 years and 7 months). Children with EoE had a significantly greater incidence of reflux symptoms, dysphagia, tracheomalacia, and 'hypoxic spells' (P < 0.05). EoE patients also underwent significantly more surgery including fundoplication and aortopexy when compared with those without EoE (P < 0.0001). Although the incidence of gastrostomy was greater in the EoE group (33% vs. 13%), this was not statistically significant. Half of the EoE patients had a coexisting atopic condition at time of diagnosis. The commonest condition was asthma 7/18 (38%) followed by specific food allergy 6/18 (33%). EoE was treated in 11 patients with either swallowed fluticasone or budesonide slurry. All improved clinically. Histologically, five had complete resolution and six had partial improvement. Six children with EoE were treated with acid suppression alone. All improved clinically, and 5/6 had subsequent histological resolution. One child who received acid suppression and an exclusion diet also improved. Seven patients (38%) had an esophageal stricture at time of EoE diagnosis. Five were dilated at time of the initial endoscopy, prior to the diagnosis of EoE being available. Two patients had resolution of their strictures on medical treatment of their EoE alone and did not require further dilatation. EoE was seen in 17% of children with EA in this study. EoE should be considered in EA patients with persistent symptoms on standard reflux treatment, increasing dysphagia, and recurrent strictures.

Comparison of percutaneous endoscopic, laparoscopic and open gastrostomy insertion in children.

PURPOSE: To compare the outcomes and complications between percutaneous endoscopic gastrostomy (PEG), laparoscopic gastrostomy (LAPG) and open gastrostomy (OG) in children. METHODS: Retrospective review of 369 patients from July 1998 to December 2010 who had their gastrostomies inserted at a single tertiary paediatric institution. Patients who were lost in follow-up (59) and had insufficient data (23) were excluded from this study. Results were analysed using descriptive statistics. RESULTS: Of the 369 included in our study, 260 patients underwent LAPG, 86 PEG and 23 open gastrostomy (OG) procedures. The early complication rate for PEGs was 10.5 %, and for LAPGS 2.7 % (p = 0.006). The late complication rate was 41.9 % for PEGs and 43.1 % for LAPGs (p = NS). The overall complication rate for PEG was 54.7 % and it was 44.6 % for LAPG (p = NS). Major complications occurred only in the PEG group: gastro-colonic fistula (1), peritonitis (1), and "buried bumper syndrome" (1). The overall complication rate for OG was 78.3 % (p = 0.01, when this was compared to LAPGs and PEGs together), although there were no early complications in the OG group. CONCLUSION: PEGs had a significantly higher early complication rate than LAPGs and the only major complications occurred in the PEG group. PEGs also had a higher overall complication rate than LAPGs, although the difference was not statistically significant. Both PEGs and LAPGs were significantly superior to OG in terms of overall complication rates.

The erythropoietin-derived peptide ARA290 reverses mechanical allodynia in the neuritis model.

Studies on the neuritis model suggest that in many patients with neuropathic pain, symptoms may be due to nerve inflammation rather than frank nerve injury. Treatments for these patients are often ineffective. The neuroprotective and hematopoietic agent erythropoietin (EPO) has been shown to reverse pain behaviors in nerve injury models and therefore may be of therapeutic benefit. However, EPO can cause thrombosis. ARA290 is an analog of EPO that has the neuroprotective activities of EPO without stimulating hematopoiesis. The present study has examined the effects of ARA290 on pain behavior in the neuritis model. Following neuritis induction, 30 or 120 µg/kg ARA290 or saline vehicle was injected intraperitoneally into rats daily from day 1 post surgery. Animals were assessed for mechanical allodynia and heat hyperalgesia. Levels of the cytokine tumor necrosis factor-α (TNF-α) and chemokine (CC motif) ligand 2 (CCL2) mRNA were also assessed using polymerase chain reaction. Vehicle-treated neuritis animals (n=20) developed signs of mechanical allodynia and heat hyperalgesia that reached a maximum on day 4 and 3 of testing, respectively. Treatment with either 30 (n=11) or 120 µg/kg ARA290 (n=9) prevented the development of mechanical allodynia. However, ARA290 did not significantly affect heat hyperalgesia. There was no significant difference between the effects of each drug dose (p<0.05, unpaired t test comparing area under the curve for mechanical allodynia). The levels of CCL2 and TNF-α mRNA in the nerve and Gelfoam were not significantly different following 120 µg/kg ARA290 treatment (n=3-7) compared to vehicle-treated animals (n=3-7; p=0.24; unpaired t tests). In summary, ARA290 may be beneficial in the treatment of neuropathic pain symptoms where signs of nerve injury are absent on clinical assessment. The mechanisms of action do not appear to involve the inhibition of TNF-α or CCL2 production.

The 2010 Royal Australasian College of Physicians' policy statement 'Circumcision of infant males' is not evidence based.

Infant male circumcision (MC) is an important issue guided by Royal Australasian College of Physicians (RACP) policy. Here we analytically review the RACP's 2010 policy statement 'Circumcision of infant males'. Comprehensive evaluation in the context of published research was used. We find that the Statement is not a fair and balanced representation of the literature on MC. It ignores, downplays, obfuscates or misrepresents the considerable evidence attesting to the strong protection MC affords against childhood urinary tract infections, sexually transmitted infections (human immunodeficiency virus, human papilloma virus, herpes simplex virus type 2, trichomonas and genital ulcer disease), thrush, inferior penile hygiene, phimosis, balanoposthitis and penile cancer, and in women protection against human papilloma virus, herpes simplex virus type 2, bacterial vaginosis and cervical cancer. The Statement exaggerates the complication rate. Assertions that 'the foreskin has a functional role' and 'is a primary sensory part of the penis' are not supported by research, including randomised controlled trials. Instead of citing these and meta-analyses, the Statement selectively cites poor quality studies. Its claim, without support from a literature-based risk-benefit analysis, that the currently available evidence does 'not warrant routine infant circumcision in Australia and New Zealand' is misleading. The Statement fails to explain that performing MC in the neonatal period using local anaesthesia maximises benefits, safety, convenience and cost savings. Because the RACP's policy statement is not a fair and balanced representation of the current literature, it should not be used to guide policy. In the interests of public health and individual well-being, an extensive, comprehensive, balanced review of the scientific literature and a risk-benefit analysis should be conducted to formulate policy.

Ultrasound-guided transversus abdominis plane blocks for laparoscopic appendicectomy in children: a prospective randomized trial.

BACKGROUND: The effect of adding transversus abdominis plane (TAP) blocks to local anaesthetic infiltration on morphine consumption and postoperative pain in children undergoing laparoscopic appendicectomy is unknown. METHODS: After random allocation, 93 children aged 7-16 were randomized to receive ultrasound-guided TAP blocks placed before surgery or not (control). All subjects had port sites infiltrated with ropivacaine and were prescribed i.v. patient-controlled analgesia (PCA) with morphine and oral paracetamol for postoperative pain. The primary outcome was the proportion of subjects using >200 µg kg(-1) morphine. Secondary outcomes included PCA morphine use, pain scores, time intervals to the first use of PCA and other analgesics, sedation scores, postoperative nausea or vomiting, and time to hospital discharge. RESULTS: The procedure duration was longer in the TAP group (111 compared with 97 min for controls, P=0.03). The duration in the recovery ward and that of the hospital stay were similar. There was no difference in the proportion of subjects requiring >200 µg kg(-1) of PCA morphine [control 31/45 (69%), TAP 29/42 (69%), P=0.99]. There was no significant difference in PCA morphine use, time intervals to the first use of PCA or other analgesics, or amounts of other analgesics. More patients in the TAP group had complicated appendicitis [TAP 13/42 (31%), control 5/45 (11%), P=0.02]. Pain scores were reduced for the TAP group in the recovery ward only (median score 0 vs 2, 95% confidence interval 0-3, P=0.03). CONCLUSIONS: TAP blocks increased anaesthesia time by 14 min on average but offered no clinically important benefit over local anaesthetic port-site infiltration to paediatric patients undergoing laparoscopic appendicectomy.

A retrospective audit of three different regional anaesthetic techniques for circumcision in children.

Postoperative analgesia for male circumcision surgery has been traditionally provided by a landmark-based dorsal penile nerve block (DPNB-LM) or by caudal epidural analgesia (CEA). In this study we report on a retrospective analysis of the effectiveness and safety of CEA, DPNB-LM and ultrasound-guided dorsal penile nerve block (DPNB-US) in our institution over a six-year period. Information was gathered from each patient's medical record. A total of 216 circumcisions were performed on patients aged from five months to 15 years. One hundred and fifteen patients received CEA, 46 DPNB-LM and 55 DPNB-US. Patients in the DPNB-LM group required rescue morphine administration in the recovery unit more frequently (30.4%) than either the DPNB-US (3.5%) or CEA groups (3.6%). Similarly, the DPNB-LM group required a larger total dose of morphine, and had longer recovery ward stays than CEA or DPNB-US groups. Time to first analgesia was greatest for the CEA group while there was no significant difference between time to first analgesia for DPNB-LM and DPNB-US. Sixty-three percent of patients in the DPNB-LM group, 1.7% of CEA and 5.5% of the DPNB-US required intraoperative opiates (P < 0.0001). There was no difference in time to hospital discharge.

Photoprotection by 1alpha,25-dihydroxyvitamin D and analogs: further studies on mechanisms and implications for UV-damage.

Ultraviolet (UV) irradiation causes DNA damage in skin cells, immunosuppression and photocarcinogenesis. 1alpha,25-dihydroxyvitamin D3 (1,25D) reduces UV-induced DNA damage in the form of cyclobutane pyrimidine dimers (CPD) in human keratinocytes in culture and in mouse and human skin. UV-induced immunosuppression is also reduced in mice by 1,25D, in part due to the reduction in CPD and a reduction in interleukin (IL-6. The cis-locked analog, 1alpha,25-dihydroxylumisterol3 (JN), which has almost no transactivating activity, reduces UV-induced DNA damage, apoptosis and immunosuppression with similar potency to 1,25D, consistent with a non-genomic signalling mechanism. The mechanism of the reduction in DNA damage in the form of CPD is unclear. 1,25D doubles nuclear expression of p53 compared to UV alone, which suggests that 1,25D facilitates DNA repair. Yet expression of a key DNA repair gene, XPG is not affected by 1,25D. Chemical production of CPD has been described. Incubation of keratinocytes with a nitric oxide donor, SNP, induces CPD in the dark. We previously reported that 1,25D reduced UV-induced nitrite in keratinocytes, similar to aminoguanidine, an inhibitor of nitric oxide synthase. A reduction in reactive nitrogen species has been shown to facilitate DNA repair, but in view of these findings may also reduce CPD formation via a novel mechanism.

Predictors of variability in urinary incontinence and overactive bladder symptoms.

AIMS: We used data from the General Longitudinal Overactive Bladder Evaluation (GLOBE) to understand predictors of variation in urgency and urinary incontinence (UI) symptoms over time. METHODS: A random sample of Geisinger Clinic primary care patients (men and women) 40+ years of age were recruited for a survey of bladder control symptoms at baseline and 12 months later. Symptom questions used a 4-week recall period. Composite scores were derived for urgency and UI frequency. Logistic regression was used to evaluate predictors of variation in scores at cross-section and longitudinally. RESULTS: A majority of those with UI symptoms and almost 40% of those with urgency symptoms reported episodes of once a week or less often; 17% had symptoms a few times a week or more often. Twenty-one percent with urgency symptoms and 25% with UI symptoms at baseline did not have active symptoms 12 months later. The strongest predictors of active symptoms at follow-up were baseline symptom score and duration of time since first onset of symptoms. Of those with no urgency symptoms at baseline, 22% had urgency at 12 months. Among those with no UI symptoms at baseline, 13% had UI symptoms 12 months later. Among the latter, age (males only) and BMI were the strongest predictors of symptoms at follow-up. CONCLUSIONS: Inter-individual and intra-individual occurrences of urgency and UI symptoms are highly variable in the general population. Use of established predictors to select individuals with less variability in symptoms may help to reduce placebo rates in clinical trials.

Use of ultrasound in 187 infants with suspected infantile hypertrophic pyloric stenosis.

The diagnostic efficacy of ultrasound (US) in the diagnosis of infantile hypertrophic pyloric stenosis (IHPS) was evaluated, with particular attention paid to whether prematurity, age or weight correlate significantly to the sonographic measurements. The medical records of 187 infants with suspected IHPS were reviewed retrospectively. Eighty-seven had an US examination with details of the pylorus. Fifty-nine of these gave a positive diagnosis. The US criteria for a positive diagnosis were pyloric muscle thickness (PMT)>or=3 mm and pyloric muscle length (PML)>or=17 mm. The mean overall PMT was 4.14 mm and mean overall PML was 18.99 mm. Premature infants had a lower mean PML (17.8 mm) than the term infants (PML mean 19.3 mm); however, this was not significant (t-value 1.92, P=0.062). The sensitivity and specificity of PMT was 91 and 85%, respectively, and of PML 76 and 85%, respectively. The ability of US to diagnose IHPS using our criteria was significant (t-value, PMT 14.93 and PML 6.89; P<0.0001). There was no significant correlation between age, weight or prematurity and a sonographic diagnosis of IHPS (Pearson's coefficient<0.3). Therefore, the same US criteria should apply irrespective of prematurity, age or weight. Borderline PMT and PML measurements necessitate repeat US or alternative imaging.

Ultrasound guided dorsal penile nerve block in children.

We describe a technique for using a portable ultrasound scanner (38 mm broadband (10-5 MHz) linear array transducer (Sonosite Titan SonoSite, Inc. 21919 30th Drive SE Bothell, WA.)) to guide dorsal penile nerve block in children under general anaesthesia. Real-time scanning is used to guide bilateral injections into the sub-pubic space, deep to Scarpa's fascia either side of the midline fundiform ligament. Scanning can confirm that the local anaesthetic has spread to contact the deep fascia on each side. A subcutaneous wheal of local anaesthetic along the penoscrotal junction completes the block.

Screening women with menorrhagia for underlying bleeding disorders: the utility of the platelet function analyser and bleeding time.

Menorrhagia is a very common clinical problem among women of reproductive age and recent studies have suggested that underlying bleeding disorders, particularly von Willebrand's deficiency and platelet function defects, are prevalent in women presenting with menorrhagia. The objective of this study was to determine the utility of the platelet function analyser (PFA-100) and bleeding time (BT) as initial screening tests for underlying bleeding disorders in women with menorrhagia. In this study, 81 women with a physician diagnosis of menorrhagia underwent PFA-100 testing, BT and comprehensive haemostatic testing. The effectiveness of the PFA-100 and BT as screening tools in women with menorrhagia was assessed using results of haemostatic testing for von Willebrand's disease (VWD) and platelet dysfunction. In women presenting with menorrhagia, the PFA-100 had a sensitivity 80%, specificity 89%, positive predictive value (PPV) 33%, negative predictive value (NPV) 98% and efficiency 88% for VWD. For platelet aggregation defects, the PFA-100 closure time had a sensitivity 23%, specificity 92%, PPV of 75%, NPV of 52% and efficiency 55%. The data suggest that the PFA-100 may be useful in stratifying women with menorrhagia for further von Willebrand testing; however, neither the PFA-100 nor the BT tests are effective for purposes of classifying women for standard platelet aggregometry testing in women presenting with menorrhagia.

Trends in clinical management of women with von Willebrand disease: a survey of 75 women enrolled in haemophilia treatment centres in the United States.

OBJECTIVE: To assess the management of women with von Willebrand disease( vWD) in an Heamophilia Treatment Center (HTC) setting. METHODS: A total of 75 women with vWd who were registered in HTCs in the United States participated in this study. A telephone interview elicited information about symptoms pertaining to bleeding disorders, diagnostic issues, referral patterns, treatment modalities before and after the enrollment in the HTC, HTC services provided, and satisfaction with care in the HTC. RESULTS: Menorrhagia was the most commonly reported symptom (84%). The average time from the first symptom until clinician recognition was 16 years (range 0-39). In HTC, DDAVP was the most commonly used drug (31%). Of the 75 women, 71 reported a strong positive opinion and satisfaction about their care in the HTCs. DISCUSSION: Women with VWD were typically diagnosed with the condition well into adulthood, in spite of the fact that majority of them experienced several bleeding symptoms beginning in early childhood. In general an HTC setting is appropriate for management of women with bleeding disorders. Diagnosis, treatment and education provided in the HTCs were viewed positively by those surveyed.

The beta fibrinogen gene G-455-A polymorphism is a risk factor for Legg-Perthes disease.

Legg-Perthes disease is a pediatric hip disorder characterized by avascular necrosis of the femoral head. The etiology of Legg-Perthes disease may involve repeated interruptions of the blood supply to the proximal femur. Thus, the role of thrombosis in Legg-Perthes disease is of interest. The focus of this analysis is an evaluation of the relationship between Legg-Perthes disease and the beta fibrinogen gene G-455-A polymorphism in 55 cases of Legg-Perthes disease and 56 age, race, and gender-matched healthy controls. Parents of subjects completed a questionnaire about their child's lifestyle and medical history. Blood was obtained for plasma and DNA analysis. Study subjects were predominantly white (93%), male (77%) and under age 16 (70%). Cases were more likely to be exposed to passive smoke than were controls (odds ratio 5.6, 95% confidence interval 2.0-12.0). Assuming a dominant genetic model, individuals who possessed either the G/A or A/A genotype were over three times more likely to have Legg-Perthes disease compared to those without the polymorphism (odds ratio 3.4, 95% confidence interval 1.5-7.8). Separate analyzes by smoke exposure revealed that the excess risk of the G-455-A polymorphism occurred in those exposed (odds ratio 7.0) as opposed to those unexposed to passive smoke (odds ratio 1.9). Although this difference in the odds ratios is not statistically significant (P=0.2), it suggests a possible interactive effect of cigarette smoke and the b fibrinogen gene G-455-A polymorphism in the risk of developing Legg-Perthes disease.

Measurement of von Willebrand factor activity: relative effects of ABO blood type and race.

Tests based on three different principles are reported to measure the activity of von Willebrand factor (VWF): ristocetin cofactor (VWF:RCo), collagen binding (VWF:CB), and the so-called "activity ELISA" (VWF:MoAb). We measured these and other diagnostic parameters in a population of 123 randomly selected female study controls, age 18-45 years. Type O subjects had significantly lower levels than non-O subjects in each test. Race differences were seen in all tests except VWF:RCo, with Caucasians having significantly lower levels than African-Americans. ABO differences accounted for 19% of the total variance in VWF:Ag (P < 0.0001) and race for 7% (P < 0.0001), for a total of 26%. Both effects were mediated through VWF:Ag and were independent. VWF:Ag level was the primary determinant of VWF function, accounting for approximately 60% of the variance in VWF:RCo and VWF:CB and 54% of the variance in factor VIII. The ratio VWF:RCo/VWF:Ag differed significantly by race within blood group. The median ratios were 0.97 for type O Caucasians vs. 0.79 for type O African-Americans and 0.94 for non-O Caucasians vs. 0.76 for non-O African-Americans. The ratio VWF:CB/VWF:Ag did not vary. This suggests racial differences in the interaction of VWF with GP1b but not with subendothelium. Alternatively, VWF:RCo may be regulated to maintain a relatively constant plasma level in the presence of excessive VWF:Ag. This heterogeneity within the normal population is partially responsible for the difficulty in defining diagnostic limits for von Willebrand disease.

Longitudinal sliding of the median nerve in patients with carpal tunnel syndrome.

In nerve compression syndromes restricted nerve sliding may lead to increased strain, possibly contributing to symptoms. Ultrasound was used to examine longitudinal median nerve sliding in 17 carpal tunnel syndrome patients and 19 controls during metacarpophalangeal joint movement. Longitudinal movement in the forearm averaged 2.62 mm in controls and was not significantly reduced in carpal tunnel syndrome (CTS) patients (mean=2.20 mm). In contrast, CTS patients had a 40% reduction in transverse nerve movement at the wrist on the most, compared to least, affected side and nerve areas were enlarged by 34%. Normal longitudinal sliding in the patients indicates that nerve strain is not increased and will not contribute to symptoms.

Platelet functional defects in women with unexplained menorrhagia.

Menorrhagia is a common clinical problem and is unexplained in more than 50% of women. Although studies suggest that von Willebrand's Disease (VWD) is found in a substantial number of women with unexplained menorrhagia, the prevalence of platelet defects in women with menorrhagia is unknown. To determine the prevalence of platelet and other hemostatic defects, we evaluated women ages 17-55 diagnosed with unexplained menorrhagia. Seventy-four women (52 white, 16 black, six other) were studied. Bleeding time was prolonged in 23 women (31.5%). Maximal percent platelet aggregation was decreased with one or more agonists in 35 (47.3%) women. The most commonly found platelet function defects were reduced aggregation responses to ristocetin in 22 women and to epinephrine in 16 women. Sixteen of 22 women with reduced ristocetin aggregation had von Willebrand ristocetin cofactor (VWF:RCo) and von Willebrand factor antigen (VWF:Ag) > 60%. Platelet ATP release was decreased with one or more agonists in 43 (58.1%) women. Of the black women studied, 11/16 (69%) had abnormal platelet aggregation studies compared with 20/52 white women (39%) (P = 0.06). Black women with menorrhagia had a higher prevalence of decreased platelet aggregation in response to ristocetin and epinephrine than did white women (P = 0.0075, P = 0.02). Ten women (13.5%) had VWF:RCo and/or VWF:Ag < 60%. Using race and blood group specific ranges, 5 (6.8%) women had decreased VWF:RCo, VWF:Ag and/or collagen binding (VWF:CB). Mild factor XI deficiency was found in two women and one woman with mild factor V deficiency and one hemophilia A carrier were identified. We conclude that the prevalence of platelet function defects and other inherited bleeding disorders is substantial in a multiracial US population of women with unexplained menorrhagia.

The epidemiology of venous thromboembolism in Caucasians and African-Americans: the GATE Study.

The aim of this study was to assess, comprehensively, medical and genetic attributes of venous thromboembolism (VTE) in a multiracial American population. The Genetic Attributes and Thrombosis Epidemiology (GATE) study is an ongoing case-control study in Atlanta, Georgia, designed to examine racial differences in VTE etiology and pathogenesis. Between 1998 and 2001, 370 inpatients with confirmed VTE, and 250 control subjects were enrolled. Data collected included blood specimens for DNA and plasma analysis and a medical lifestyle history questionnaire. Comparing VTE cases, cancer, recent surgery, and immobilization were more common in caucasian cases, while hypertension, diabetes, and kidney disease were more prevalent in African-American cases. Family history of VTE was reported with equal frequency by cases of both races (28-29%). Race-adjusted odds ratios for the associations of factor V Leiden and prothrombin G20210A mutations were 3.1 (1.5, 6.7) and 1.9 (0.8, 4.4), respectively. Using a larger external comparison group, the odds ratio for the prothrombin mutation among Caucasians was a statistically significant 2.5 (1.4, 4.3). A case-only analysis revealed a near significant interaction between the two mutations among Caucasians. We found that clinical characteristics of VTE patients differed across race groups. Family history of VTE was common in white and black patients, yet known genetic risk factors for VTE are rare in African-American populations. Our findings underscore the need to determine gene polymorphisms associated with VTE in African-Americans.

Effects on axonal conduction of anti-ganglioside sera and sera from patients with Guillain-Barré syndrome.

The efficacy of plasma exchange as a therapy for Guillain-Barré syndrome (GBS) suggests that humoral factors might contribute to the axonal conduction block responsible for the major symptoms of the disease. To explore this possibility, we have applied sera to rat spinal roots in vitro while monitoring axonal conduction. Neither fresh sera from 12 patients with GBS or Miller-Fisher syndrome (MFS), nor serum from rabbits immunised with Campylobacter jejuni from patients with GBS, MFS or gastroenteritis were effective in causing acute conduction block, despite the presence of antibodies to gangliosides GD3, GM1, GQ1b and GT1a. Potential explanations are advanced.

Medical, reproductive and psychosocial experiences of women diagnosed with von Willebrand's disease receiving care in haemophilia treatment centres: a case-control study.

OBJECTIVE: To assess the medical, gynaecological and reproductive experiences of women with von Willebrand's disease (VWD) and to evaluate the impact of VWD on mental health and life activities. METHODS: A total of 102 women with VWD who were registered in haemophilia treatment Centres (HTCs) in the United States and 88 controls were interviewed regarding medical, gynaecological and reproductive history, life activities and symptoms of depression. Symptoms of depression were measured using the Center for Epidemiological Studies Depression Scale (CES-D). RESULTS: Excessive bleeding symptoms were reported in 74% of VWD cases compared with 6% of controls. Women with VWD had a higher prevalence of menorrhagia, excessive postpartum bleeding, other gynaecological conditions, arthritis and migraine headaches than did controls. More VWD cases than controls reported that menstruation had a negative impact on overall life activities. No difference in the prevalence of depression was found between cases and controls. DISCUSSION: Women with VWD experience menorrhagia and other gynaecological conditions at a higher frequency than women without bleeding disorders. Menstruation in women with VWD has a negative impact on life activities. The prevalence of depression was not elevated in this group of women whose VWD is being managed in an HTC.