Patterns of tertiary prophylaxis in Canadian adults with severe and moderately severe haemophilia B.

From a young age patients with severe and moderately severe FIX deficiency (haemophilia B) can experience spontaneous or traumatic bleeding and joint destruction may result. The use of coagulation factor IX concentrate to prevent anticipated bleeding, as primary or secondary prophylaxis, has become a common and recommended practice in children. The current practice of using tertiary prophylaxis, in the presence of established joint arthropathy, in adults with haemophilia B is not well characterized. This observational study was conducted to gain a better understanding of the recent Canadian experience with tertiary prophylaxis in adults with severe and moderately severe haemophilia B. Data were collected from all eligible adult (≥ 18 years of age) males with baseline FIX:C ≤ 2% from seven Canadian Hemophilia Treatment centres over a 2-year observation period from 2009 to 2011. Thirty-four per cent of the 67 subjects with moderately severe haemophilia B were exposed to prophylaxis with the majority as continuous prophylaxis (≥45 weeks year(-1) ). The severe subgroup (FIX:C < 1%) demonstrated a 52% exposure rate. None had primary prophylaxis exposure in childhood. Eighty-one per cent used once or twice weekly infusion regimens and reported a median annual bleeding rate of five bleeds per year versus four bleeds per year for those using on-demand treatment. Annual median factor utilization for all subjects using prophylaxis was 196,283 U year(-1) compared to 46,361 U year(-1) for on demand. Approximately 50% of adults with severe haemophilia B are using continuous tertiary prophylaxis in Canada, a practice likely to increase which warrants further study.

Suspected collagen disorders in the bleeding disorder clinic: a case-control study.

Disorders of collagen are associated with a mild bleeding tendency because of the potential abnormal interaction of collagen, von Willebrand factor (VWF) and platelets required during primary haemostasis and due to generalized soft tissue fragility. Abnormal collagen may contribute to bleeding in existing mucocutaneous bleeding disorders, but the prevalence in this setting is unknown. Generalized symptomatic joint hypermobility (SJH) is common in collagen disorders and may be objectively measured. To assess the association between symptomatic joint hypermobility and mucocutaneous bleeding disorders, we performed a case-control study in which case subjects were 55 consecutive individuals who had visited our bleeding disorder clinic with a diagnosis of von Willebrand disease, low von Willebrand factor levels, mild platelet function disorder or undefined bleeding disorder. Controls were 50 subjects without a bleeding disorder, and were age and gender matched to the cases. All subjects were assessed with: (i) Beighton score for joint hypermobility, (ii) revised Brighton criteria, (iii) Condensed MCMDM1-VWD bleeding questionnaire, and (iv) haemostasis laboratory studies. The prevalence of SJH/suspected collagen disorder in the bleeding disorder clinic was 24% (13/55) compared with 2% (1/50) in the control population (OR 15, 95% CI 2-121). Seventy-seven per cent of bleeding disorder clinic SJH subjects (10/13) had a prior personal or family history of Ehlers-Danlos, Benign Joint Hypermobility Syndrome or Osteogenesis Imperfecta (OI). Symptomatic joint hypermobility was associated with increased odds of an underlying mucocutaneous bleeding disorder. These findings suggest that a collagen disorder is common and often unrecognized in the bleeding disorder clinic as a potential contributor to the bleeding symptoms.

A study of thrombophilia testing and counseling practices of family physicians using the script concordance method in Calgary, Canada.

BACKGROUND: Thrombophilia testing helps to identify populations at risk of venous thromboembolism, but motivations for testing individuals are frequently unclear. OBJECTIVES: Our goals were to assess the motivations for thrombophilia testing among family physicians (FPs) to determine whether testing was congruent with expert opinion, and to study counseling practices. METHODS: The FPs and experts completed a survey involving hypothetical thrombophilia patients. Responses between groups were compared using the script concordance method. RESULTS: The FPs referred 35.9% of cases. Of the five scenarios, two resulted in disagreement regarding appropriateness of testing (P ≤ .037). The FPs were more likely to test male, obese, or pediatric patients, patients with a family history of myocardial infarction or infertility, and patients with a recent event (P ≤ .043). The FPs were more likely to counsel patients after testing (P ≤ .016). CONCLUSION: Disagreement exists between physician groups about the utility of thrombophilia testing. Self-reported lack of pretest counseling among FPs warrants further study.

Auras are frequent in idiopathic generalized epilepsy.

The occurrence of an aura is often considered evidence of a partial rather than an idiopathic generalized epilepsy syndrome. The authors examined this hypothesis by prospectively recording reports of auras by patients being admitted for video-EEG monitoring. Auras were equally common (70%) among patients with idiopathic generalized epilepsy as they were among those with localization-related epilepsy. Presence of an aura is not a reliable indicator of localization-related epilepsy.

Depression but not seizure frequency predicts quality of life in treatment-resistant epilepsy.

BACKGROUND: The two-thirds of patients with epilepsy who become seizure-free have a quality of life (QOL) similar to the general population. The major treatment challenge is patients with refractory epilepsy. Whereas neurologists typically focus on seizure reduction in the treatment of these patients, results of studies relating seizure frequency to QOL are conflicting. As depression is associated with reduced QOL in epilepsy and antiepileptic medications (AEDs) can cause depression, it is important to determine the relative roles of depression and seizure frequency in QOL in refractory epilepsy. METHODS: Prospective evaluation was conducted of patients with refractory epilepsy being admitted to an inpatient video-EEG monitoring unit. The impact of clinical variables (age, sex, marital status, seizure frequency, duration and type of seizure disorder, seizure localization, number of AEDs, depression) on QOL was analyzed. RESULTS: Depression was a powerful predictor of QOL (n = 122, beta = -35.8, p < 0.0001). No other variable predicted QOL. Depression was common (54%), severe (19% with suicidal thoughts), underdiagnosed (37%), and largely untreated (17% on antidepressants). CONCLUSIONS: Treatment of depression may be inadequately prioritized in the management of intractable epilepsy.

Complex syntax production of African American preschoolers.

This study examined changes in the complex syntax production of 85 3- and 4-year-old African American children and the role of child (i.e., gender, age, African American English) and family (i.e., home environment) factors. The mean percentage of utterances containing one or more complex syntax forms was 6.2% at 3 years and 11.7% at 4 years. Girls produced more complex syntax forms than did boys. Complex syntax production increased significantly between age 3 and age 4 and correlated positively with mean length of utterance in words. Children from more responsive and stimulating home environments produced more complex syntax at 4 years. African American English was not related to the amount of complex syntax used.

Cellular uptake of taurine by lactating porcine mammary tissue.

Milk taurine plays a critical role in neonatal development. Taurine uptake in lactating sow mammary tissue has not been characterized previously. The kinetic properties, ion dependence and substrate specificity of taurine uptake were characterized in mammary tissue collected from lactating sows at slaughter. Tissue explants were incubated in an isosmotic physiologic buffer with [3H]taurine tracer to measure taurine uptake. Taurine uptake was dependent upon the presence of extracellular sodium and chloride ions, which is consistent with the co-transport of sodium and chloride with taurine. Uptake was not dependent upon ion exchange mechanisms or upon furosemide-sensitive ion co-transport. Taurine uptake was saturable and exhibited an apparent Km of 20 microM and a V(max) of 386 micromol/kg cell water/30 min. Substrate specificity studies indicated a strong interaction of beta-amino acids with the taurine transport system. Taurine transport in lactating sow mammary tissue is therefore a high affinity, sodium-dependent mechanism specific for beta-amino acids, and is analogous to sodium-dependent taurine uptake in other tissues. The high affinity and high specificity of the taurine uptake system allows for concentration of taurine within the mammary cell and is ultimately responsible for provision of taurine required for neonatal development.

Cellular uptake of valine by lactating porcine mammary tissue.

The cellular uptake of branched-chain amino acids in mammary tissue is important for understanding their role in milk synthesis in the sow. This study characterized the kinetic properties and substrate specificity of the valine uptake system in the porcine mammary gland. Mammary tissue was collected from lactating sows at slaughter and tissue explants were incubated in media containing isosmotic salt and amino acids of interest, plus [3H]valine tracer. Valine uptake was time-dependent and was dependent on the presence of sodium, as indicated by a reduction in uptake when sodium in the medium was replaced by choline. The valine transport system in porcine mammary tissue had a Km of 0.64 mM, a Vmax of 1.84 mmol-kg cell water(-1) 30 min(-l), and a Kd (diffusion constant) of 1.16 L x kg cell water(-1) x 30 min(-1). Valine uptake was inhibited by leucine and alpha-aminoisobutyric acid and by high concentrations of L-alanine, L-lysine, cycloleucine, L-glutamine, and L-methionine, but not by 2-(methyl-amino)-isobutyric acid. This transport system is the primary system responsible for uptake of valine, and probably other branched-chain amino acids, in lactating sow mammary tissue. Physiological concentrations of valine in the blood are below the Km of the specific valine transport system and well below the diffusion uptake capabilities. The kinetic parameters of this valine transport system should not be limiting to valine uptake for milk protein synthesis. However, competition of valine uptake with branched-chain amino acids, as well as with other amino acids, may affect valine uptake in lactating tissue.

Otitis media in childhood in relation to preschool language and school readiness skills among black children.

OBJECTIVE: To examine whether otitis media with effusion (OME) and associated hearing loss (HL) during the first 5 years of life were related to children's language skills during the preschool years and to school readiness skills at entry to kindergarten. METHODS: In a prospective study, the ears of 85 black children primarily from low-income families and recruited from community-based childcare programs were repeatedly examined from 6 months to 5 years of age for the presence of OME and from 6 months to 4 years of age for HL when well and ill with OME. Assessments were made annually of the children's child-rearing environments at home and in childcare, and children's language skills between 3 and 5 years of age and readiness skills in literacy and math were evaluated at entry into kindergarten. RESULTS: Children had either bilateral or unilateral OME approximately 30.4% and HL 19.6% of the observation time. OME and associated HL were significantly positively correlated with some measures of expressive language at 3 and 4 years of age; however, these direct relationships were no longer significant when the child's gender, socioeconomic status, maternal educational level, and the responsiveness and support of the home and childcare environments were also considered. Further, both OME and HL were moderately correlated with school readiness skills at entry to school, with children having more OME scoring lower in verbal math problems and with children with more HL scoring lower in math and recognizing incomplete words. These associations continued to remain significant even after partialing out the child and family background factors. CONCLUSIONS: There was not a significant relationship between children's early OME history or HL and language skills during the preschool years. However, children with more frequent OME had lower scores on school readiness measures. These associations were moderate in degree, however, and the home environment was more strongly related to academic outcomes than was OME or HL. These results should be interpreted cautiously when generalizing to other populations.

Expression and putative role of neuropilin-1 in the early scaffold of axon tracts in embryonic Xenopus brain.

Although the general principles of axon guidance in vitro are understood, little is known about how axons respond to the myriad of cues in vivo and navigate axon pathways within the complex milieu of the embryonic brain. Although neuropilin-1 is an axon guidance receptor for chemorepulsive ligands in the class 3 subfamily of semaphorins, its role in directing axon growth in vivo is unknown. In the present study, we have examined the expression and role of neuropilin-1 in the embryonic forebrain of Xenopus. Neuropilin-1 was selectively expressed by a subset of axons in the early scaffold of axon tracts. These axons arise from the presumptive telencephalic nucleus, cross the rostral midline by means of the postoptic commissure, and enter the major longitudinal tract of the prosencephalon, the tract of the postoptic commissure. At the level of the mesencephalon, these axons diverge and enter one of two axon tracts: either the ventral longitudinal tract or the ventral commissure. This same population of axons also expresses NOC-2, a novel glycoform of the neural cell adhesion molecule N-CAM. We have previously revealed the presence of a chemorepulsive activity underlying the pathway followed by these axons as they cross the ventral commissure. When neuropilin-1 was overexpressed after blastomere injections of synthetic RNA transcripts, NOC-2 axons entered the ventral commissure but failed to cross the midline. Instead, these axons were inhibited from growing ventrally within the commissural pathway. These results suggest that the level of neuropilin-1 in the NOC-2 subpopulation of axons is critical for determining whether these axons reach the ventral midline. Thus, neuropilin-1 may a specific role in directing the growth of NOC-2 axons across the ventral midline in the early embryonic mesencephalon.

DCC plays a role in navigation of forebrain axons across the ventral midbrain commissure in embryonic xenopus.

In the developing vertebrate brain, growing axons establish a scaffold of axon tracts connected across the midline via commissures. We have previously identified a population of telencephalic neurons that express NOC-2, a novel glycoform of the neural cell adhesion molecule N-CAM that is involved in axon guidance in the forebrain. These axons arise from the presumptive telencephalic nucleus, course caudally along the principal longitudinal tract of the forebrain, cross the ventral midline in the midbrain, and then project to the contralateral side of the brain. In the present study we have investigated mechanisms controlling the growth of these axons across the ventral midline of the midbrain. The axon guidance receptor DCC is expressed by the NOC-2 population of axons both within the longitudinal tract and within the ventral midbrain commissure. Disruption of DCC-dependent interactions, both in vitro and in vivo, inhibited the NOC-2 axons from crossing the ventral midbrain. Instead, these axons grew along aberrant trajectories away from the midline, suggesting that DCC-dependent interactions are important for overcoming inhibitory mechanisms within the midbrain of the embryonic vertebrate brain. Thus, coordinated responsiveness of forebrain axons to both chemostimulatory and chemorepulsive cues appears to determine whether they cross the ventral midline in the midbrain.

Self-administered intraurethral chlorpromazine: an unusual cause of priapism.

Priapism is a prolonged, painful penile erection unaccompanied by sexual desire and not alleviated by ejaculation. The etiologies of priapism are numerous and diverse. Priapism can be a serious adverse effect of psychotropic medications. The case of a 36-year-old man who demonstrated priapism, 48 hours after inserting a crushed chlorpromazine tablet into the urethral meatus of his penis, is reported. Priapism induced by this route of drug administration has not been previously described. The pathophysiology and treatment of priapism are reviewed.

Differences and similarities in development of drinking behavior between alcoholic offspring of alcoholics and alcoholic offspring of non-alcoholics.

Self-reported initial, early, and long-term drinking behaviors, experiences, and consequences were obtained from male alcoholics completing inpatient treatment. Subjects were recruited and selected on the basis that they met DSM-III criteria for diagnosis of alcohol dependency and that their biological fathers were alcoholic (FHP; Family History Positive) or that they had no biological family history of alcoholism (FHN; Family History Negative). Results indicated that FHP subjects rated their initial taste of beer higher than FHN subjects, that FHP subjects began tasting and subsequently regularly drinking alcohol at an earlier age than FHN subjects and that there was significantly shorter elapsed time between initiating regular drinking and developing alcoholic-symptomatic problems in living among FHP alcoholics than FHN alcoholics. Although there were a few other significant differences, the drinking-behavioral histories of the two groups were remarkably similar and parallel. Taken together, results suggest that familial risk factors primarily influence the rate at which alcoholic drinking and alcoholism develop, rather than the form or pattern of alcoholic drinking.

Endocarditis due to six entrapped pacemaker leads and concomitant recurrent coronary arteriosclerosis.

A case of endocarditis associated with six entrapped endocardial pacer leads is presented. Because of many failed attempts at removing them by conservative measures, cardiopulmonary bypass was needed; concomitant redo coronary bypass grafts were done. To our knowledge, this represents a unique case, the like of which has not been reported previously. Salient features of management are discussed.