Valnoctamide as a valproate substitute with low teratogenic potential in mania: a double‐blind,controlled, add‐on clinical trial

Bersudsky Y, Applebaum J, Gaiduk Y, Sharony L, Mishory A, Podberezsky A, Agam G, Belmaker RH. Valnoctamide as a valproate substitute with low teratogenic potential in mania: a double‐blind, controlled, add‐on clinical trial.
Bipolar Disord 2010: 12: 376–382. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Valproic acid’s well‐known teratogenicity limits its use in women of childbearing age. Valnoctamide is an analog of valproate that does not undergo biotransformation to the corresponding free acid. In mice, valnoctamide has been shown to be distinctly less teratogenic than valproate. Valnoctamide is an anticonvulsant, and we hypothesized that valnoctamide is antimanic. Methods: We performed a double‐blind, five‐week, add‐on, controlled trial of valnoctamide in mania. Patients were treated with risperidone at doses of the physician’s discretion. Valnoctamide or placebo was begun at doses of 600 mg/day and increased to 1200 mg after four days. Weekly ratings by a psychiatrist blind to the study drug were conducted using the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale (YMRS), and the Clinical Global Impression (CGI). Results: Fifteen valnoctamide patients and 17 placebo patients completed at least one post‐baseline week and were included in data analysis. In all efficacy measures valnoctamide was more effective than placebo as an add‐on to risperidone, using two‐way analysis of variance (ANOVA) with time as the within‐subject factor. Two‐way ANOVA showed a significant effect of time (p < 0.001) and significant interaction between treatment and time (YMRS: p = 0.012; BPRS: p = 0.007; CGI: p = 0.003). Differences between valnoctamide and placebo were significant from week 3 to week 5. Conclusion: Valnoctamide could be an important valproate substitute for women of childbearing age with bipolar disorder who may become pregnant.     

Perinatal outcomes in inflammatory bowel disease

Objective: To determine whether inflammatory bowel disease (IBD) is associated with increased risk for adverse perinatal outcome.

Methods: A case–control study of 116 singleton pregnancies with IBD compared to 56?398 singleton controls delivered between 1986 and 2001.

Results: Patients with IBD were slightly older (32.8 vs. 30.6 years, p <?0.001), more likely to be Caucasian or Asian than Black or Latino (92% vs. 57%, p <?0.001) and have private health insurance (33% vs. 3%, p <?0.001). IBD was associated with an increased risk for labor induction (32% vs. 24%, p?=?0.002), chorioamnionitis (7% vs. 3%, p?=?0.04) and Cesarean section (32% vs. 22%, p?=?0.007), but there were no differences in neonatal outcomes. Subgroup analysis demonstrated an increased risk for low birth weight (LBW) in the ulcerative colitis group vs. the Crohn's disease group (19% vs. 0%, p?=?0.002). Patients with prior surgery for IBD had a lower incidence of LBW (0% vs. 12%, p?=?0.03). Flares during pregnancy were associated with an increased risk for preterm delivery (27% vs. 8%, p?=?0.02) and LBW (32% vs. 3%, p?=?0.003).

Conclusion: IBD was an independent risk factor for Cesarean section but there was no increase in adverse perinatal outcome. Crohn's disease, prior IBD surgery and quiescent disease were associated with a lower risk for LBW.     

Radiation dose reduction during hysterosalpingography: an application of scanning-beam digital radiography

Hysterosalpingography was performed in 31 patients by means of a low-dose scanning-beam digital radiographic system. The technique permits adequate evaluation of gynecologic abnormalities while allowing significant reduction in radiation: 2.4-mR (6.1 X 10(-7) C/kg) exposure to the skin and 0.7-mrad (7 X 10(-6) Gy) mean dose to the ovaries per image obtained. Sixteen patients demonstrated readily recognizable and documented abnormalities, corroborated by laparoscopy, laparotomy, or other supportive evidence.     

Platelet kinetics in patients with idiopathic thrombocytopenic purpura and moderate thrombocytopenia

We studied ten normal subjects and 20 patients with stable, untreated idiopathic thrombocytopenic purpura (ITP) and platelet counts in the range of 35,000 to 110,000/microL. The diagnosis was made by clinical criteria. Platelet-associated IgG was increased in all nine of the nine patients studied. Autologous platelets were labeled with chromium 51 and reinfused for measurement of mean cell life and platelet production rate. Mean cell life was calculated by two methods, weighted mean and multiple hit, with excellent agreement between the two. As expected, mean cell life was significantly reduced in ITP patients as compared to the normal subjects (2.9 days v. 8.0 days, P less than .001). However, mean platelet production rates in ITP patients and normal subjects, 3.5 and 3.8 X 10(9) platelets/k/d respectively, were not significantly different. Platelet production rate was above and below the normal range (2 to 5.6 X 10(9) platelets/k/d) in two and four patients, respectively. We conclude that the rate of platelet production is not increased in most patients with ITP who have platelet counts greater than 35,000/microL. We did find that platelet size was increased in eight of the 12 patients in whom it was measured, including two of the patients with low platelet production.     

Elevation of cerebrospinal fluid soluble CD27 levels in patients with meningeal localization of lymphoid malignancies [published erratum appears in Blood 1996 Oct 1;88(7):2818]

Diagnosis of meningeal localization of lymphoid malignancies by means of cytologic examination of the cerebrospinal fluid (CSF) can be difficult. Thus far no reliable CSF tumor markers have been identified. CD27 is a transmembrane disulfide-linked 55-kD homodimer present on most peripheral blood T cells and on a subset of B cells. CD27 is also expressed on human malignant B cells and high levels of soluble CD27 can be present in the serum of patients with B-cell malignancies. The aim of this study is to determine prospectively the diagnostic value of CSF sCD27 as a tumor marker in patients with meningeal localization of lymphoid malignancies. CSF sCD27 levels were determined by sandwich enzyme-linked immunosorbent assay. The optimal cut-off value using receiver operator characteristics curves was found to be 10 U/mL. sCD27 levels were normal in all 50 control patients (lumbar disc protrusion) and in 39 of 40 samples obtained from patients with either solid tumors or acute myeloid leukemia. Of 104 CSF samples from 70 children with acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) undergoing routine central nervous system (CNS) staging, sCD27 was false positive and false negative in only one sample each. In 70 samples from 45 patients suspected of meningeal localization of ALL or NHL, the sCD27 test had an excellent sensitivity (100%) and specificity (82%). In 7 patients with positive CSF studied longitudinally, sCD27 levels correlated very well with remission and relapse. sCD27 levels were not nonspecifically increased by the administration of cytostatic drugs. Finally, sCD27 was also elevated in the 4 patients studied with primary central nervous system lymphoma (PCNSL). CSF sCD27 is a promising tumor marker in patients with either meningeal localization of lymphoid malignancies or PCNSL, and can be useful in the differential diagnosis of CNS involvement by either lymphoid malignancies or solid tumors.