LORAZEPAM IN STUPOR

SUMMARY The use of lorazepam in relieving catatonic symptoms is illustrated by the dramatic response in a stuporous patient. The treatment allows further investigations and management. It is recommended that clinicians familiarise themselves with this simple pharmacological intervention.     

Patients with a deficiency of natural killer cell activity lack the VEP13-positive lymphocyte subpopulation

Many patients with B-type chronic lymphocytic leukemia (CLL) exhibit a profound defect in their natural killer (NK) cell activity, the basis of which is still obscure. Hence, we analyzed the NK cells from peripheral blood samples from 11 patients with CLL for phenotype and function, after removal of the leukemic cells with a monoclonal antibody (BA-1) plus complement. Phenotypic analysis of these nonleukemic cells with monoclonal antibodies (MoAbs) against NK cells revealed that the CLL patients had higher percentages of HNK-1-positive cells (23.5% compared to controls with 14.7%). In contrast, VEP13- positive cells were absent or low in seven patients (0.8% compared to controls with 11.2%) and normal in four patients (10.5%). When testing NK cell activities against K562 or MOLT 4 target cells, patients with no or minimal numbers of VEP13-positive cells were found to be deficient, while patients with normal percentages of VEP13-positive cells had NK cell activity comparable to controls. Isolation by fluorescence-activated cell sorter of HNK-1-positive cells from patients lacking VEP13-positive cells and NK cell activity indicated that the majority of the HNK-1-positive cells in these patients had the large granular lymphocyte morphology that is characteristic of NK cells. Thus, the deficiency of NK cell activity in CLL patients appears to result from the absence of cells carrying the VEP13 marker.     

Familial systemic mastocytosis with germline KIT K509I mutation is sensitive to treatment with imatinib,dasatinib and PKC412

Mastocytosis are myeloproliferative neoplasms commonly related to gain-of-function mutations involving the tyrosine kinase domain of KIT. We herein report a case of familial systemic mastocytosis with the rare KIT K509I germ line mutation affecting two family members: mother and daughter. In vitro treatment with imatinib, dasatinib and PKC412 reduced cell viability of primary mast cells harboring KIT K509I mutation. However, imatinib was more effective in inducing apoptosis of neoplastic mast cells. Both patients with familial systemic mastocytosis had remarkable hematological and skin improvement after three months of imatinib treatment, suggesting that it may be an effective front line therapy for patients harboring KIT K509I mutation.     

Immunomodulatory agents in myelofibrosis

INTRODUCTION: The treatment options for patients with myelofibrosis (MF) remain limited. Anemia, thrombocytopenia, extramedullary hematopoiesis, constitutional symptoms, and disease progression are the primary causes of morbidity and mortality. Traditional non-transplant therapies remain non-curative. Moreover, in the JAK2 inhibitor era, no single pharmacologic agent has been shown to improve all MF-related clinical manifestations. Immunomodulatory agents (IMiDs), such as thalidomide and lenalidomide, have been useful in the treatment of some MF patients while newer IMiDs such as pomalidomide are showing promise in MF. AREAS COVERED: This review focuses on the biologic rationales of IMiDs and the clinical results supporting their use in MF. It includes data on the new IMiD, pomalidomide and also explores the possible utility of combining IMiDs with other agents. A PubMed search of articles related to IMiDs and myelofibrosis were conducted. Relevant studies and clinical studies with sample size of > 15 were included. EXPERT OPINION: In the JAK2 inhibitor era, IMiDs are alternative treatments in managing splenomegaly and constitutional symptoms. They remain useful in the treatment of cytopenias. Pomalidomide's good anemia response may lead to its inclusion as one of the frontline anemia therapies in MF. Molecular biomarkers may allow us to identify patients who will respond to IMiDs.     

Cannabidivarin is anticonvulsant in mouse and rat

Background and Purpose

Phytocannabinoids in Cannabis sativa have diverse pharmacological targets extending beyond cannabinoid receptors and several exert notable anticonvulsant effects. For the first time, we investigated the anticonvulsant profile of the phytocannabinoid cannabidivarin (CBDV) in vitro and in in vivo seizure models.

Experimental Approach

The effect of CBDV (1–100 μM) on epileptiform local field potentials (LFPs) induced in rat hippocampal brain slices by 4-aminopyridine (4-AP) application or Mg²⁺-free conditions was assessed by in vitro multi-electrode array recordings. Additionally, the anticonvulsant profile of CBDV (50–200 mg·kg⁻¹) in vivo was investigated in four rodent seizure models: maximal electroshock (mES) and audiogenic seizures in mice, and pentylenetetrazole (PTZ) and pilocarpine-induced seizures in rats. The effects of CBDV in combination with commonly used antiepileptic drugs on rat seizures were investigated. Finally, the motor side effect profile of CBDV was investigated using static beam and grip strength assays.

Key Results

CBDV significantly attenuated status epilepticus-like epileptiform LFPs induced by 4-AP and Mg²⁺-free conditions. CBDV had significant anticonvulsant effects on the mES (≥100 mg·kg⁻¹), audiogenic (≥50 mg·kg⁻¹) and PTZ-induced seizures (≥100 mg·kg⁻¹). CBDV (200 mg·kg⁻¹) alone had no effect against pilocarpine-induced seizures, but significantly attenuated these seizures when administered with valproate or phenobarbital at this dose. CBDV had no effect on motor function.

Conclusions and Implications

These results indicate that CBDV is an effective anticonvulsant in a broad range of seizure models. Also it did not significantly affect normal motor function and, therefore, merits further investigation as a novel anti-epileptic in chronic epilepsy models.

Linked Articles

This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.167.issue-8     

Hyperammonaemic encephalopathy in an adult patient with citrin deficiency associated with a novel mutation

We report on an adult patient with citrin deficiency in Hong Kong, in whom a novel mutation was identified. The patient presented with recurrent hyperammonaemic encephalopathy due to impairment of the liver urea cycle enzyme argininosuccinate synthetase. This autosomal recessive condition is also characterised by interesting food preferences, notably aversion to carbohydrates and craving for protein-rich and/or lipid-rich foods, as well as neuropsychiatric symptoms. Plasma amino acid analysis is very useful in revealing urea cycle disorders, and mutational analysis of the SLC25A13 gene can confirm the diagnosis.