Clock drawing in children with perinatal stroke.

BACKGROUND: Children with perinatal stroke may show evidence of contralateral spatial neglect. The goal of this study was to determine whether the Clock Drawing Test commonly used in adults to identify neglect would be effective in detecting neglect in children with perinatal stroke. METHODS: Thirty-eight individuals (age range 6-21 years) with left hemisphere or right hemisphere perinatal onset unilateral lesions and 179 age-matched controls were given a free-drawn Clock Drawing Test in a cross-sectional design. An adapted scoring system that evaluated right- and left-sided errors separately was developed as part of the investigation. RESULTS: Children with right hemisphere lesions made a greater number of errors on both the right and left sides of the clock drawings in all age subgroups (6-8 years, 9-14 years, and 15-21 years) compared with controls. Children with right hemisphere lesions showed greater left and right errors in the younger groups compared with controls, with significantly poorer performance on the left at 6-8 years, suggestive of contralateral neglect. However, by ages 15-21 years, the right hemisphere lesion subjects no longer differed from controls. CONCLUSIONS: Clock drawing can identify spatial neglect in children with early hemispheric damage. However, brain development is a dynamic process, and as children age, spatial neglect may no longer be evident. These findings demonstrate the limitations of predicting long-term outcome after perinatal stroke from early neurocognitive data. Children with perinatal stroke may require different neural pathways to accomplish specific skills or to overcome deficits, but ultimately they may have "typical" outcomes.

Exploring the Plasmodium falciparum cyclic-adenosine monophosphate (cAMP)-dependent protein kinase (PfPKA) as a therapeutic target.

One of the prototype mammalian kinases is PKA and various roles have been defined for PKA in malaria pathogenesis. The recently described phospho-proteomes of Plasmodium falciparum introduced a great volume of phospho-peptide data for both basic research and identification of new anti-malaria therapeutic targets. We discuss the importance of phosphorylations detected in vivo at different sites in the parasite R and C subunits of PKA and highlight the inhibitor sites in the parasite R subunit. The N-terminus of the parasite R subunit is predicted to be very flexible and we propose that phosphorylation at multiple sites in this region likely represent docking sites for interactions with other proteins, such as 14-3-3. The most significant observation when the P. falciparum C subunit is compared to mammalian C isoforms is lack of phosphorylation at a key site tail implying that parasite kinase activity is not regulated so tightly as mammalian PKA. Phosphorylation at sites in the activation loop could be mediating a number of processes from regulating parasite kinase activity, to mediating docking of other proteins. The important differences between Plasmodium and mammalian PKA isoforms that indicate the parasite kinase is a valid anti-malaria therapeutic target.

The conservative management of interstitial pregnancy.

OBJECTIVES: To evaluate the effectiveness of systemic methotrexate in the treatment of interstitial pregnancy. DESIGN: Prospective observational study. SETTING: An Early Pregnancy Assessment Unit in a London teaching hospital. SAMPLE: Twenty consecutive women diagnosed with an interstitial pregnancy. METHODS: Women were diagnosed with an interstitial pregnancy based on transvaginal ultrasound findings. Single dose, intramuscular methotrexate was administered on day 0. A second dose of methotrexate was given if the beta-hCG levels had not fallen by 15% between days four and seven. Weekly follow up continued until the serum beta-hCG < 5 IU. MAIN OUTCOME MEASURE: The resolution of serum beta-hCG levels without the need for surgical intervention. RESULTS: Two hundred and ninety-three ectopic gestations were diagnosed over a 42-month period. Twenty of these were interstitial in nature, with a median initial serum beta-hCG of 6452 IU. Of the 20 interstitial pregnancies, 17 cases received systemic methotrexate. Sixteen were treated successfully (94%), including all of the four cases with fetal heart activity present. A second methotrexate dose was given to six patients. Two cases were managed expectantly. Two cases underwent laparotomy and cornual resection: one elected for surgical management at the outset and one as a result of suspected ectopic rupture after two doses of methotrexate. There were no other complications. CONCLUSIONS: Systemic methotrexate is a safe and highly effective treatment for interstitial pregnancy. Surgery can be avoided in the majority of women with this condition. Early recognition of the cornual pregnancy with transvaginal ultrasound is essential.