Neutrophil Activation in Immunoadsorption

Abstract: Immunoadsorption therapy (IAT) is used in the treatment of autoimmune diseases. Although IAT has been reported to modify humoral immunity by inducing chemokines and activating complements, much remains unknown about the biological effects of IAT on cellular components in peripheral blood. To define the influence of IAT on leukocytes, we determined leukocyte l ‐selectin (CD62L) and Mac‐1 (CD11b) as parameters for activation of leukocytes in peripheral blood during IAT. Peripheral leukocyte l ‐selectin and Mac‐1 were determined continuously by flow cytometry in 6 patients with neuroimmunological disorders in whom IAT was conducted using a Plasma Flow OP‐05 (Asahi Medical Corp., Tokyo, Japan) as a plasma separator and Immusorba TR‐350 (Asahi Medical Corp., Tokyo, Japan) as an adsorption column. Expression of neutrophils (PMN) l ‐selectin was decreased 30 min after starting IAT, with the decreases particularly marked at the end of IAT, while expression of mononuclear cells (MNC) l ‐selectin slightly increased during IAT. Expression of PMN Mac‐1 was markedly increased at the end of IAT, whereas expression of MNC Mac‐1 did not change during IAT. Leukocyte counts decreased 30 min after starting IAT, and then increased to the initial level or higher in parallel with l ‐selectin downregulation and Mac‐1 upregulation on PMN. l ‐selectin downregulation and Mac‐1 upregulation on PMN suggested that activation of PMN associated with changes in peripheral leukocyte counts occurred during IAT and might play some role in modulating the human circulating blood and immune systems.     

Intubating laryngeal mask for fibreoptic intubation — particularly useful during neck stabilization

PURPOSE: To assess the ease of fibrescope-assisted tracheal intubation while the patient's head and neck were placed in the neutral or the manual in-line position, and to determine if the intubating laryngeal mask facilitated fibreoptic intubation in these positions. METHODS: In 84 patients, the patient's head and neck were placed in the neutral position (pillow placed under occiput), and in another 40 patients the head and neck were stabilized by the manual in-line method (no pillows under occiput). In both groups, after induction of anesthesia with 2.0-2.5 mgxkg(-1) propofol, 50-100 microg fentanyl and 1.0 mgxkg(-1) vecuronium, patients were allocated randomly into two groups: in Group C tracheal intubation was attempted using only a fibrescope, whereas in Group L fibreoptic intubation through the intubating laryngeal mask was attempted. RESULTS: In group C the success rate of fibreoptic tracheal intubation within two minutes was higher in the neutral position (31 of 42 patients (73%)) than in the manual in-line position (8 of 20 patients (40%)). In contrast, in group L the success rate was similar between the two positions. Tracheal intubation was easier in group L than in group C (P < 0.01 or 0.001) and the time for intubation was shorter in group L than in group C in both head and neck positions. CONCLUSIONS: Fibreoptic tracheal intubation was more difficult in the manual in-line position than in the neutral position. The intubating laryngeal mask facilitated fibreoptic intubation in both positions.     

Evaluation of topotecan monotherapy for relapsed small-cell lung cancer after amrubicin monotherapy failure

Objective: The utility of topotecan monotherapy for relapsed small-cell lung cancer (SCLC) after failure of amrubicin monotherapy has not been evaluated. We aimed to investigate the efficacy and safety of topotecan monotherapy in patients with relapsed SCLC after amrubicin monotherapy.Patients and Methods: We retrospectively analyzed data from 16 patients with relapsed SCLC who were treated with topotecan monotherapy after amrubicin monotherapy at our hospital.Results: The response rate, progression-free survival, and overall survival were 0%, 32.5 days (95% confidence interval [CI] = 18–51), and 112 days (95% CI = 55–267), respectively. The most common adverse events (grade ≥3) were leukopenia (31.3%) and thrombocytopenia (31.3%), followed by anemia, anorexia, edema, and lung infections.Conclusion: The efficacy of topotecan monotherapy for relapsed SCLC after amrubicin monotherapy is inconclusive. Therefore, further studies are warranted.     

Meticulous closure of collateral vessels in the perihilar mediastinal pleura to control intraoperative bleeding during lung transplantation for pulmonary hypertension

BackgroundMassive blood transfusion compensating hemorrhage during lung transplantation (LT) results in primary graft dysfunction (PGD) and worse outcomes after LT. Collateral vessels in the perihilar mediastinal pleura could be the source of hemorrhage during LT in patients with pulmonary hypertension (PH). The purpose of this study was to examine the effect of closure with hemoclips of the vessels in the perihilar mediastinal pleura on the risk of intraoperative hemorrhage and outcomes after LT in patients with PH.MethodsWe retrospectively reviewed 80 patients who underwent LT, including 13 patients with primary PH, 29 patients with secondary PH, and 38 patients with non-PH.ResultsThe median number of hemoclips was significantly higher in the primary PH group than in the non-PH group (P=0.0045) or secondary PH group (P=0.0060). The intraoperative blood loss, transfusion volume, maximum PGD grade, and the 30-day and 90-day mortality rates in the primary PH group were equivalent to those in the other two groups.ConclusionsMeticulous closure of collateral vessels in the perihilar mediastinal pleura during LT in patients with primary PH allowed intraoperative hemorrhage to be controlled and might be associated with acceptable mortality rate in these patients similar to that of LT in patients with other diseases.     

Novel Therapeutic Method for Unresectable Pancreatic Cancer—The Impact of the Long-Term Research in Therapeutic Effect of High-Intensity Focused Ultrasound (HIFU) Therapy

High-intensity focused ultrasound (HIFU) is a novel advanced therapy for unresectable pancreatic cancer (PC). HIFU therapy with chemotherapy is being promoted as a novel method to control local advancement by tumor ablation. We evaluated the therapeutic effects of HIFU therapy in locally advanced and metastatic PC. PC patients were treated with HIFU as an optional local therapy and systemic chemotherapy. The FEP-BY02 (Yuande Bio-Medical Engineering) HIFU device was used under ultrasound guidance. Of 176 PC patients, 89 cases were Stage III and 87 were Stage IV. The rate of complete tumor ablation was 90.3%, while that of symptom relief was 66.7%. The effectiveness on the primary lesions were as follows: complete response (CR): n = 0, partial response (PR): n = 21, stable disease (SD): n = 106, and progressive disease (PD): n = 49; the primary disease control rate was 72.2%. Eight patients underwent surgery. The median survival time (MST) after diagnosis for HIFU with chemotherapy compared to chemotherapy alone (100 patients in our hospital) was 648 vs. 288 days (p < 0.001). Compared with chemotherapy alone, the combination of HIFU therapy and chemotherapy demonstrated significant prolongation of prognosis. This study suggests that HIFU therapy has the potential to be a novel combination therapy for unresectable PC.     

Physiological properties of the mauthner system in the adult zebrafish

We investigated the morphological and electrophysiological properties of the Mauthner (M-) cell and its networks in the adult zebrafish (Danio rerio) in comparison with those in the goldfish (Carassius auratus). The zebrafish M-cell has an axon cap, a high resistivity structure which surrounds the initial segment of the M-axon, and accounts for an unusual amplification of the fields generated within and around it. Second, extra- and intracellular recordings were performed with microelectrodes. The resting potential was ∼−80 mV with an input resistance of ∼0.42 MΩ. The M-cell extracellular field was large (10-20 mV), close to the axon hillock, and the latency of antidromic spikes short (∼0.4 milliseconds), confirming a high conduction velocity in the M-axon. The extrinsic hyperpolarizing potential (EHP), which signals firing of presynaptic cells and collateral inhibition, was markedly lower at frequencies of spinal stimulation > ∼5/second, suggesting an organization of the recurrent collateral network similar to that in the goldfish. Inhibitory postsynaptic potentials (IPSPs) were highly voltage-dependent; their decay time constant was increased by depolarizations. The presynaptic neurons which are numerous could be identified by their passive hyperpolarizing potential (PHP) produced by the M-spike current. Auditory responses, mediated via mixed synapses (electrical and chemical), had short delays and hence are well suited to trigger the escape reaction. The similarities of their properties indicate that the wealth of information generated over decades in the goldfish can be extrapolated to the zebrafish. J. Comp. Neurol. 395:493–509, 1998. © 1998 Wiley-Liss, Inc.     

Identification of recurrent and novel mutations in the LDL receptor gene in Japanese familial hypercholesterolemia

We used the denaturing gradient gel electrophoresis (DGGE) method to investigate 120 Japanese patients with familial hypercholesterolemia (FH) for mutations in the promoter region and the 18 exons and their flanking intron sequence of the low density lipoprotein (LDL) receptor gene. Fourteen aberrant DGGE patterns were found, and the underlying mutations were characterized by DNA sequencing. Five novel missense mutations (C317S, F382L A410T, L547V, and E693K), two nonsense mutations (W512X and K790X), four frameshift mutation (355del7, 1246ins5, 1687ins1, and 2035ins1), one splicing mutation (1845+2 T→C), and two inframe mutations (661ins21 and 1115del9/ins6) were identified. Six of these mutations (L547V, E693K, W512X, 355del7, 1687ins1, and 20354ins1) have not been described before in FH. These newly identified mutations cosegregated in their family members with defective LDL receptor activity and hypercholesterolemia, and are thought to be causal for the FH phenotype. These results demonstrate that there is a broad spectrum of mutations in the LDL receptor gene in the Japanese population. Hum Mutat 14:87, 1999. © 1999 Wiley‐Liss, Inc.