Long-term valproate and lamotrigine treatment may be a marker for reduced growth and bone mass in children with epilepsy

PURPOSE: To determine whether long-term treatment with valproate (VPA) and/or lamotrigine (LTG) in children with epilepsy is associated with altered growth and/or bone metabolism. METHODS: Twenty-seven boys and 26 girls, aged 3 to 17 years (9.2 +/- 3.9, mean +/- SD), with epilepsy treated with VPA and/or LTG for > or =2 years were evaluated for growth, nutrient intakes, physical activity, bone mineral density (BMD), and blood biochemical indices of mineral and bone metabolism. RESULTS: Twenty-three (43.4%) of the children had a body height below the 10th percentile. Z-scores for BMD below -1.5 occurred in 24.4% of the children. When patients were divided into two groups according to daily activity score, a significantly lower Z-score for total body BMD (p = 0.007), percentile for body height (p = 0.05), and plasma parathyroid hormone (PTH; p = 0.04), osteocalcin (p = 0.04) and 25-hydroxyvitamin D (25OHD) (p = 0.01) were found in the inactive compared with the active group. Z-score for total body BMD was correlated with daily activity score (r = 0.43, p = 0.008). Plasma intact osteocalcin and intact PTH values correlated significantly (r = 0.36, p = 0.02). Plasma 1,25-dihydroxyvitamin D was within normal range for all subjects. When patients were divided into LTG-alone, VPA-alone, and LTG-plus-VPA treatment groups, significantly lower (p < 0.05) plasma osteocalcin and percentile for body height were found in the VPA-plus-LTG treatment group. CONCLUSIONS: Long-term VPA and LTG therapy, particularly when combined, is associated with short stature, low BMD, and reduced bone formation. These alterations may be mediated primarily through reduced physical activity rather than through a direct link to the VPA and/or LTG therapy.     

Clinical applications and future trends in cardiac CTA

The new 64-slice multi-detector computed tomographic scanners with improved temporal and special resolution are well suited to cardiac scanning allowing large area coverage and very short scan time. Current applications include plaque and stenosis assessment, evaluation of bypass graft patency and stenosis, coronary artery anomalies and recently, assessment of implanted coronary stents. Possible fields of utilization include emergency room triage of chest pain, and screening prior to invasive angiography in order to reduce the load of invasive studies. The future holds the prospect of automatic analysis of coronary plaque and luminal stenosis possibly opening up a new vista for non-invasive risk assessment.     

Protection of cultured Cyprinus carpio against a lethal viral disease by an attenuated virus vaccine

Massive mortality of koi and common carp--Cyprinus carpio species--has been observed since 1998 in many countries worldwide, resulting in severe economic losses. The cause of the disease is an as yet unclassified large DNA virus, designated carp nephritis gill necrosis virus (CNGV) or koi herpes virus (KHV). Previously, we demonstrated that the wild type CNGV lost its pathogenecity following serial transfer in cell culture, and that clones isolated from the attenuated population can be used as a prophylactic vaccine. Here, we describe the basic conditions required for proper fish immunization so that a protection protocol may be devised. We demonstrated that carps are very sensitive to the pathogenic and the attenuated viruses, and short immersion of fish in water containing the viruses is sufficient for infection. The infection of fish with the pathogenic and the attenuated viruses is temperature-restricted; fish held at the non-permissive temperature, immediately following infection, were not affected by the pathogenic virus, and were not rendered resistant to the disease. Thus, propagation of the virus in the fingerlings is a pre-requisite for immunization. In order to increase the number of random mutations in the genome of the attenuated virus, and thus, reduce the possibility of the attenuated virus reverting to pathogenic, we irradiated it and selected additional clones appropriate for vaccination. The results of our study suggest that a safe and efficient prophylactic vaccine can be developed by selecting an appropriate attenuated virus.     

Cesarean section: Does it really prevent the development of postpartum stress urinary incontinence? a prospective study of 363 women one year after their first delivery

AIMS: Stress urinary incontinence (SUI) in young women is usually the result of pelvic floor injury during vaginal delivery. Whether cesarean section delivery may prevent such injury is questionable. We undertook a prospective study to compare the prevalence of SUI among primiparae 1 year after spontaneous vaginal delivery versus elective cesarean section, or cesarean section performed for obstructed labor. METHODS: Three hundred and sixty-three consecutive primiparae were recruited immediately after delivery and were followed for 1 year. Women were asked upon recruitment whether they had ever experienced SUI before pregnancy. Those who had SUI before pregnancy were excluded. Thus, only cases of de novo childbirth-associated SUI were analyzed. Patients were divided into three subgroups according to the mode of delivery: spontaneous vaginal delivery (n = 145), elective cesarean section (n = 118), and cesarean section performed for obstructed labor (n = 100). Patients who underwent elective cesarean section were not given a trial of labor. Cesarean sections for obstructed labor were performed at a mean cervical dilatation of 8.7 +/- 1.6 cm and arrest of 184 +/- 24 min. Prevalence, frequency, and severity of postpartum SUI, as well as demographic and obstetric parameters, were analyzed in each subgroup. RESULTS: The three subgroups were comparable with respect to maternal age, weight, and height. Prevalence of postpartum SUI was similar after spontaneous vaginal delivery (10.3%) and cesarean section performed for obstructed labor (12%). However, SUI was significantly less common following elective cesarean section with no trial of labor (3.4%, P < 0.05). Approximately half of the symptomatic patients in each subgroup reported either moderate or severe symptoms, however, only 15-18% expressed their desire for further evaluation. CONCLUSIONS: Prevalence of postpartum SUI is similar following spontaneous vaginal delivery and cesarean section performed for obstructed labor. It is quite possible that pelvic floor injury in such cases is already too extensive to be prevented by surgical intervention. Conversely, elective cesarean section, with no trial of labor, was found to be associated with a significantly lower prevalence of postpartum SUI. Whether the prevention of pelvic floor injury should be an indication for elective cesarean section is yet to be established.     

Hypereosinophilic syndrome in a child presenting as eosinophilic pharyngitis

A 3-year-old child with idiopathic hypereosinophilic syndrome (IHES) presented with sore throat and pharyngeal exudate. Recurrent throat cultures were negative and microscopic section of the exudate revealed an extensive eosinophilic infiltration. Fourteen months later, the child still has marked hypereosinophilia and pharyngeal involvement without other organ involvement. Eosinophilic pharyngitis may be a target organ in IHES. The benign clinical course and the laboratory characteristics are described.     

Functional impairment of the vestibular end organ resulting from impulse noise exposure

OBJECTIVES/HYPOTHESIS: To assess the effect of exposure t o impulse noise, known to cause damage tothe cochlea, on the vestibular part of the inner ear using short latency vestibular evoked potentials (VsEPs), which is a direct and objective test for evaluating the function of the vestibular end organs. STUDY DESIGN: Prospective animal study. METHODS: Sand rats (Psammomys obesus) underwent baseline measurements of VsEPs in response to linear and angular acceleration stimuli and measurement of the auditory nerve and brainstem evoked response (ABR). The animals were then exposed to 10 gunshots generating impulse noise at an intensity of approximately 160 dB sound pressure level (SPL). Repeat measurements of the evoked potentials were conducted 2 to 4 hours, 1 week, and 6 weeks after the exposure. The amplitude and latency of the first wave of VsEPs in response to linear and angular acceleration stimuli, reflecting the function of the otolith organs and semicircular canals respectively, were compared between baseline and post-exposure measurements, as were ABR thresholds. RESULTS: The amplitude of the first wave of the VsEPs in response to linear acceleration was significantly (P <.001) reduced and the latency significantly (P <.005) prolonged 2 to 4 hours after the exposure in comparison to baselinemeasurements. The latency prolongation persisted in follow-up measurements, whereas the amplitude showed partial recovery. The first wave of VsEPs in response to angular acceleration was unchanged long-term. ABR thresholds were elevated in the long-term by 60 dB. CONCLUSION: It seems that impulse noise not only damages the cochlea, but also causes clear functional impairment to the vestibular end organs, mainly the otolith organs.     

The opposing effects of endothelin-1 and C-type natriuretic peptide on apoptosis of neonatal rat cardiac myocytes

C-type natriuretic peptide (CNP) and endothelin-1 are paracrine peptides with opposing effects on cardiac myocyte contraction and intracellular cGMP production. Elevated levels of both endothelin-1 and CNP are found in patients with congestive heart failure. These factors may be related to positive and negative regulation of cell apoptosis in the failing heart. To evaluate the effect of CNP and endothelin-1 on apoptosis of cardiac myocytes and the possible mechanisms involved, primary cardiac myocytes were prepared from neonatal Sabra rats. Cardiomyocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Annexin V in situ staining. The TUNEL method was used to measure the apoptotic index. CNP and the cGMP derivative, 8-br-cGMP, induced apoptosis of cardiac myocytes. CNP-induced apoptosis could be blocked by HS 142-1 (a mixture of 20-30 kinds of linear beta-1, 6-glucan esterified by capronic acid, an antagonist of type A and B natriuretic peptide receptors), and KT 5823 (C29H25N3O5), the inhibitor of cGMP-dependent protein kinase). Alpha-difluoromethylornithine (DFMO), the irreversible inhibitor of ornithine decarboxylase, also induced apoptosis to a similar extent. CNP and 8-br-cGMP caused a marked reduction of intracellular ornithine decarboxylase expression, as determined by Western blot analysis and immunohistochemical assay. Preincubation with endothelin-1 attenuated CNP- and 8-br-cGMP-induced cardiomyocyte apoptosis. Endothelin-1 also antagonized the CNP- and 8-br-cGMP-induced reduction of intracellular ornithine decarboxylase expression. These results suggest that CNP has a proapoptotic effect on neonatal rat cardiac myocytes. The effect is mediated via natriuretic peptide receptors and is due to an elevation of intracellular cGMP, which reduces the expression of intracellular ornithine decarboxylase and probably the production of polyamines. Endothelin-1 protects cardiac myocytes against CNP-induced apoptosis by influencing the cGMP-dependent pathway, and this effect is probably mediated through both a reduction of cGMP and antagonism of the CNP-induced reduction of intracellular ornithine decarboxylase expression.