Successful hyperbaric oxygen therapy for refractory BK virus-associated hemorrhagic cystitis after cord blood transplantation.

BK virus-associated hemorrhagic cystitis (BKV-HC) is a common and major cause of morbidity in recipients of allogeneic hematopoietic stem cell transplantation. A 32-year-old woman developed severe BKV-HC on day 24 after cord blood transplantation (CBT). Despite supportive therapies - such as hyperhydration, forced diuresis, and urinary catheterization - macroscopic hematuria and bladder irritation persisted for over a month. Hyperbaric oxygen (HBO) therapy at 2.1 atmospheres for 90 min per day was started on day 64 after CBT. Macroscopic hematuria resolved within a week, and microscopic hematuria was no longer detectable within 2 weeks. Hematuria did not recur after 11 sessions of HBO therapy, and no significant side effects were observed during or after treatment. HBO therapy could thus be useful in controlling refractory BKV-HC after CBT.

Attenuating effect of H+K+ATPase inhibitors on airway cough hypersensitivity induced by allergic airway inflammation in guinea-pigs.

BACKGROUND: Gastrooesophageal reflux (GER) is a frequent cause of chronic cough. Several investigators have indicated that inhibitors of H(+)K(+)ATPase (proton pump inhibitors; PPIs) could relieve coughing via inhibition of acid reflux. However, we considered that PPIs might directly inhibit increased cough reflex sensitivity. OBJECTIVE: The present study was designed to examine whether PPIs directly inhibit antigen-induced increase in cough reflex sensitivity and to elucidate the mechanism. METHODS: Actively sensitized guinea-pigs were challenged with aerosol antigen (ovalbumin, OVA) and cough reflex sensitivity to inhaled capsaicin was measured 24 h later. The PPIs (omeprazole and rabeprazole) or the histamine H(2) blocker cimetidine were administered intraperitoneally 1 h before OVA challenge and before measuring cough reflex sensitivity, then bronchoalveolar lavage fluid (BALF) was immediately collected. The pH of the fluid obtained by bronchial washing was determined after examining the effect of rabeprazole on the cough response to capsaicin. RESULTS: The number of coughs elicited by capsaicin was significantly increased 24 h after challenge with OVA compared with saline, indicating antigen-induced increase in cough reflex sensitivity. Both PPIs dose dependently and significantly inhibited antigen-induced cough hypersensitivity. Omeprazole did not influence the antigen-induced increase in the total number of cells or ratio (%) of eosinophils in BALF. Cimetidine did not affect the antigen-induced cough hypersensitivity or cellular components of BALF. The pH of the bronchial washing fluid was significantly decreased in antigen-challenged animals. Rabeprazole did not affect the antigen-induced decrease in the pH of bronchial washing fluid. CONCLUSION: These findings show that PPIs, but not histamine H(2) blockers, can directly decrease antigen-induced cough reflex hypersensitivity, while the mechanism remains unclear.

Beneficial effect of JTV-803, a new synthetic inhibitor of activated factor X, against both lipopolysaccharide-induced and tissue factor-induced disseminated intravascular coagulation in rat models.

We examined whether JTV-803, a specific activated factor X inhibitor independent of antithrombin III (ATIII), is effective against disseminated intravascular coagulation (DIC) in rat models induced by tissue factor (TF) or lipopolysaccharides (LPS). In male Wistar rats, DIC was induced by a 4 h infusion of thromboplastin (3.75 U/kg) or LPS (50 mg/kg). The rats were given JTV-803 (0.3 or 3 mg/kg, bolus intravenously) (JTV-803 groups) or low molecular weight heparin (LMWH groups) (200 U/kg, bolus intravenously) prior to an injection of TF or LPS. The results showed that JTV-803 was dose-dependently effective against DIC in both TF-induced and LPS-induced rat models. This anti-DIC effect of JTV-803 at higher doses was almost equivalent to that of LMWH in both types of DIC. Plasma ATIII activity was more prominent in the group treated with JTV-803 than in that treated with LMWH. None of rats died in the TF-induced DIC model with or without drug administration. On the contrary, seven of 22 rats died (mortality rate, 31.8%) in the LPS-induced DIC model without drug administration. Although the mortality rate of rats induced with LPS and treated with LMWH was quite high (6/16, 37.5%), none of the LPS-induced rats treated with JTV-803 died. These findings suggested that JTV-803 can treat both TF-induced and LPS-induced DIC models, and that this drug has greater potential in preserving ATIII and in improving the prognosis of DIC.

[Successful treatment of recurrent chronic myelogenous leukemia in allogeneic marrow transplant recipient with the donor leukocyte transfusion, without induction of acute graft-versus-host disease].

A 45-year-old female developed cytogenetic relapse of chronic myelogenous leukemia 4 years after allogeneic bone marrow transplantation. To induce a graft-versus-leukemia effect, peripheral blood buffy-coat cells were collected from the original marrow donor during 5 rounds of leukapheresis over 3 weeks, and 2.47 x 10(8) cells/kg were infused into the patient. Acute graft-versus-host disease (GVHD) did not develop even after an interval of 50 days from the last donor leukocyte transfusion (DLT). However, karyotypic analysis of bone marrow cells performed on the same day showed an apparent decrease in the proportion of Ph1 chromosome-positive cells (1/20) among all dividing cells, compared with the proportion (13/20) observed before DLT. At the same time, the proportion of red blood cells (RBCs) of donor origin among the peripheral RBCs of the patient, which was less than 10% before DLT, began to rise and reached 100% at 4 months after DLT. The karyotype of bone marrow cells obtained on day 90 after DLT was completely normal. Although chronic GVHD of the buccal mucosa and liver developed in association with pancytopenia on day 71 after DLT, this improved rapidly with oral administration of cyclosporine. The clinical course of this patient suggests that acute GVHD is not a prerequisite for elimination of Ph1-positive cells by DLT.

The cerebral cortex origin of enflurane-induced generalized seizure in cats.

The role of sensorimotor cortex (anterior and posterior sigmoid gyri) as the origin of enflurane-induced generalized seizures was examined and compared to that of lidocaine-induced seizures in cats. The inhaled enflurane concentration was adjusted at 3.5% in oxygen, the maximum potency to induce generalized seizures. Repetitive electrical stimulation with supramaximum intensity at a forepaw (2 Hz, 0.5 ms, 10 V) induced generalized seizures, which ended with a sudden appearance of isoelectricity in the electroencephalogram (EEG), the so-called "postictal depression." Repetitive auditory stimuli also induced similar grand mal-type EEGs. Unilateral ablation of the sensorimotor cortex completely blocked the induction of generalized seizures by contralateral somatosensory stimuli. However, it had little effect on the induction of seizures by ipsilateral somatosensory stimuli or bilateral auditory stimuli. In contrast, bilateral ablation of the sensorimotor cortex did not have a significant effect on the lidocaine-induced seizures. These findings indicate that the involvement of the sensorimotor cortex is essential for the development of enflurane-induced but not lidocaine-induced seizures.

Ascending projections of posterior canal-activated excitatory and inhibitory secondary vestibular neurons to the mesodiencephalon in cats.

The axonal projections of 62 posterior canal (PC)-activated excitatory and inhibitory secondary vestibular neurons were studied electrophysiologically in cats. PC-related neurons were identified by monosynaptic activation elicited by electrical stimulation of the vestibular nerve and activation following nose-up rotation of the animal's head. Single excitatory and inhibitory neurons were identified by antidromic activation following electrical stimulation of the contralateral and ipsilateral medial longitudinal fasciculus, respectively. The oculomotor projections of identified neurons were confirmed with a spike-triggered averaging technique. The axonal projections of the identified neurons were then studied by systematic, antidromic stimulation of the mesodiencephalon. Excitatory neurons showed two main types of axonal projections. In one type, axonal branches were issued to the interstitial nucleus of Cajal, central gray, and thalamus including the ventral posterolateral, ventral posteromedial, ventral lateral, ventral medial, centromedian, central lateral, lateral posterior, and ventral lateral geniculate nuclei. The other type was more frequently observed, giving off axon collaterals to the above-mentioned regions and to Forel's field H as well. Inhibitory neurons issued axonal branches to limited areas which included the central gray, interstitial nucleus of Cajal, its adjacent reticular formation and caudalmost part of Forel's field H, but not the rostral part of the Forel's field H and the thalamus. These results suggest that PC-related excitatory neurons participate in the genesis of vertical eye movements and in the perception of the vestibular sensation, and that PC-related inhibitory neurons seem to take part only in the genesis of vertical eye movements.

Effect of organic germanium compound (Ge-132) on experimental osteoporosis in rats.

1. The therapeutic effect of organic germanium compound, 2-carboxyethylgermaniumsesquioxide (Ge-132), for experimental osteoporosis was studied using ovariectomized rats maintained on a low calcium containing diet. 2. Serum calcitonin (sCT) level was decreased and serum parathyroid hormone (sPTH) level was increased by ovariectomy and the decrement and increment rates, respectively, were reduced by administration of Ge-132. Thus, the sCT/sPTH ratio was greater in the groups given Ge-132, indicating that the resorption was somehow inhibited by Ge-132. 3. The transverse strength of femur bone was significantly enhanced by Ge-132. 4. A trend was found in the group given Ge-132 for a larger femur cortical bone index. 5. The relative femur bone wet weight was greater in the group given Ge-132. 6. These results indicate that Ge-132 prevents decreased bone strength, and affects the femur cortical bone index, and bone mineral mass caused by osteoporosis.

High-dose ketamine does not induce c-Fos protein expression in rat hippocampus.

The effects of high-dose ketamine on the c-fos protein (c-Fos) expression were investigated in rat by an immunohistochemical technique. The administration of 100 mg/kg ketamine i.p. induced seizure-like activity (limbic seizure). No c-Fos immunoreactivity was observed in hippocampus, piriform cortex and amygdala, while it was observed in neocortex and thalamus. These findings disagree with the reports that ketamine depresses the neuronal function of the neocortex and thalamus, while it stimulates the limbic system.

Direct inhibitory synaptic connections of pontine omnipause neurons with burst neurons in Forel's field H related to vertical saccades in the cat.

This study investigated synaptic connections of omnipause neurons (OPNs) in the midline pontine tegmentum with medium-lead burst neurons (BNs) in Forel's field H (FFH), using the spike-triggered averaging technique in chronically prepared alert cats. OPNs were identified behaviorally by tonic firing during the intersaccadic period, whereas medium-lead BNs were identified by spike bursts during upward or downward saccades. A positive shift of field potential in the BN area, associated with suppression of the BNs' bursts, was observed during tonic firing of OPNs and during microstimulation in the OPN area. Averaging of BN area field potentials triggered by spikes of single OPNs on both sides, which were antidromically evoked from the BN area, revealed positive waves with monosynaptic latencies. These results strongly suggest that OPNs on both sides make direct inhibitory synaptic connections with vertical eye movement-related medium-lead BNs in the FFH.