Purification of human blood basophils using negative selection by flow cytometry

Basophils were purified from peripheral blood of normal donors using Percoll discontinuous gradients and negative selection by flow cytometry. The mean purity of basophils obtained was 84.7 +/- 4.1 (s.d.)% (range 77.3-90.0%, n = 13). The overall yield of these procedures was 16.0 +/- 2.6% (range 11.0-19.9%, n = 13), and cell viability of purified basophils exceeded 90%. Properties of highly purified basophils obtained by flow cytometry did not differ from those of partially enriched basophil preparations from Percoll discontinuous gradients in respect of: (i) intracellular histamine content; (ii) percentage of spontaneous histamine release in buffer; and (iii) percentage of histamine release triggered by ionophore A 23187 or anti-IgE. Moreover, purified basophils responded chemotactically to complement C5a in a dose-dependent manner. These findings suggest that our procedure for purification of human basophils does not affect the functions of basophils and may be useful for in vitro studies on the role of basophils in hypersensitivity reactions such as bronchial asthma.     

Clinical pharmacological study of a plasma‐derived factor VIIa and factor X mixture (MC710) in haemophilia patients with inhibitors – Phase I trial

Summary. MC710, a combined product of plasma‐derived activated factor VII (FVIIa) and factor X (FX) at a protein weight ratio of 1:10, is a novel bypassing agent for haemostasis in haemophilia patients with inhibitors. In this study, pharmacokinetic (PK), pharmacodynamic (PD) parameters and safety of single doses of MC710 were investigated in 11 male haemophilia patients with inhibitors in a non‐bleeding state. This was a multi‐centre, open‐labelled, non‐randomized, active controlled crossover, dose‐escalation study of five doses (20–120 μg kg⁻¹ of FVIIa) with re‐administration of different MC710 dosages to the same subjects. The active controls were NovoSeven (120 μg kg⁻¹) and/or FEIBA (50 and 75 U kg⁻¹) which were used to compare PD parameters. The area under the curve (AUC) and maximum plasma concentration (C_max) of MC710 active ingredients increased dose‐dependently within the range of 20 and 120 μg kg⁻¹. After administration of MC710, activated partial thromboplastin time (APTT) was dose‐dependently improved and prothrombin time (PT) was shortened to approximately 6 s at 10 min, and APTT improvement and PT shortening effects were maintained until 12 h after administration of MC710 at all doses. No serious or severe adverse event was observed after administration of MC710; furthermore, several diagnostic marker values and those changes did not indicate any signs of disseminated intravascular coagulation (DIC). These results suggest that MC710 would have haemostatic potential equal to or greater than NovoSeven and FEIBA and was be tolerable when given at doses up to 120 μg kg⁻¹.     

Inhaled nitric oxide and extracorporeal membrane oxygenation in persistent pulmonary hypertension of the newborn

Persistent pulmonary hypertension of the newborn (PPHN) may occasionally require an invasive treatment with extracorporeal membrane oxygenation (ECMO). Inhaled nitric oxide (NO) has recently been introduced as a selective pulmonary vasodilator for treatment of PPHN. We describe a case of PPHN in which neither inhaled NO nor ECMO was effective in reversing pulmonary hypertension. The clinical course of the patient suggested a potential role of NO inhalation in predicting the outcome of ECMO treatment for PPHN.     

Night-time hypnopompic visual hallucinations related to REM sleep disorder

Abstract We encountered three patients who had experienced hypnopompic visual night-time hallucinations. Their clinical manifestations resembled Charles Bonnet's syndrome and the content of their experiences were understood as attempts at wish fulfillment. However, abnormal REM findings were recognized on polysomnogram at the occurrence of visual hallucination in two cases. We speculated that dysfunction of REM sleep mechanism might contribute to the night-time occurrence of such kind of visual hallucination and that their visual experiences might be reflected by dream content.     

Testicular Toxicity of Gallium Arsenide, Indium Arsenide, and Arsenic Oxide in Rats by Repetitive Intratracheal Instillation

The testicular toxicities of two compound semiconductor materials,gallium arsenide (GaAs) and indium arsenide (InAs), and arsenicoxide (As₂O₃) were examined in rats by repetitive intratrachealinstillation of these substances in suspension twice a week,a total of 16 times. A single instillation dose was 7.7 mg/kgin the GaAs and the InAs groups and 1.3 mg/kg in the As₂O₃ group.A significant decrease in sperm count and significant increasein the proportion of morphologically abnormal sperm were foundin the epididymis in the GaAs group. Especially, abnormal spermwith a straight head increased markedly in this group. In theGaAs–treated rats, there was 40-fold increase in the degeneratinglate elongated spermatids at the postspermiation stages, stagesIX, XI, and XI. From these results, it is indicated that GaAsdisturbed the spermatid head transformation at the late spermiogenicphases and caused spermiation failure. InAs caused a sperm countdecrease in the epididymis, though its testicular toxicity wasrelatively weak compared with that of GaAs. As₂O₃, a probabledissolution arsenic product of GaAs and InAs in vivo, did notshow any testicular toxicities in this study. It seems likelythat, along with arsenics, gallium and indium play a role inthe testicular toxicities of GaAs and InAs.     

Tetracycline and niacinamide control bullous pemphigoid but not pemphigus foliaceus when these conditions coexist

Pemphigus and pemphigoid are different types of autoimmune bullous disease and can occur in the same patient. We report a female patient with this condition. At first, we diagnosed her with bullous pemphigoid, and we treated her with tetracycline, niacinamide and a topical steroid. Tense bullas disappeared shortly after that, but crusted erythemas mainly on her head and trunk persisted. We examined BP180 and desmoglein 1 enzyme‐linked immunosorbent assays, and also histological features, which showed coexistence of bullous pemphigoid and pemphigus foliaceus concurrently. Therefore, we tried prednisolone, which could control both conditions. This case showed that tetracycline and niacinamide could control bullous pemphigoid, but could not control pemphigus foliaceus, and that prednisolone was effective for both conditions.