A phase II trial of stereotactic body radiotherapy in 4 fractions for patients with localized prostate cancer.

PURPOSE/OBJECTIVE(S): To report results from our phase II study of stereotactic body radiotherapy (SBRT) delivering 36 Gy in 4 fractions for patients with localized prostate cancer. MATERIALS/METHODS: We enrolled 55 patients treated with SBRT delivering 36 Gy in 4 fractions between 2015 to 2018. All patients were categorized as low-risk (n = 4), intermediate-risk (n = 31) or high-risk (n = 20) according to National Comprehensive Cancer Network criteria. Median age was 73 years (range 54-86 years). Two-thirds of patients (n = 37) had received androgen-deprivation therapy for 3-46 months (median, 31 months). Median duration of follow-up was 36 months (range 1-54 months). We used Radiation Therapy Oncology Group and National Cancer Institute-Common Toxicity Criteria version 4 for toxicity assessments. Quality of life (QOL) outcomes were also evaluated using the Expanded Prostate Cancer Index Composite (EPIC). RESULTS: Protocol treatments were completed for all patients. Six patients experienced biochemical failures. Among these six patients, three patients experienced clinical failure. One patient showed bone metastasis before biochemical failure. One patient died of gastric cancer. The 3-year biochemical control rate was 89.8%. Acute grade 2 genitourinary (GU) and gastrointestinal (GI) toxicities were observed in 5 patients (9%) and 6 patients (11%), respectively. No grade 3 or higher acute toxicities were observed. Late grade 2 GU and GI toxicities were observed in 7 patients (13%) and 4 patients (7%), respectively. Late grade 3 GU and GI toxicities were observed in 1 patient (1.8%) each. EPIC scores decreased slightly during the acute phase and recovered within 3 months after treatment. CONCLUSION: Our phase II study showed that SBRT delivering 36 Gy in 4 fractions was safe and effective with favorable QOL outcomes, although this regimen showed slightly more severe toxicities compared to current standards.

Multicenter randomized phase II study of cisplatin and fluorouracil plus docetaxel (DCF) compared with cisplatin and fluorouracil plus Adriamycin (ACF) as preoperative chemotherapy for resectable esophageal squamous cell carcinoma (OGSG1003).

BACKGROUND: This phase II trial evaluated the efficacy of cisplatin and fluorouracil (CF)-based combination neoadjuvant chemotherapy on the outcome of patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). We compared the recurrence-free survival (RFS) associated with CF plus Adriamycin (ACF) with that associated with CF plus docetaxel (DCF) to select an alternative regimen in a new phase III trial investigating the optimal neoadjuvant treatment of patients with ESCC. PATIENTS AND METHODS: Patients with resectable advanced ESCC were randomly assigned to either ACF (Adriamycin 35 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 7 days) every 4 weeks or DCF (docetaxel 70 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 5 days) every 3 weeks. Surgery was scheduled after completion of two cycles of chemotherapy. The primary end point was RFS, analyzed by the intention-to-treat. RESULTS: Between October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, all of whom were eligible and randomly assigned to the two groups (81 to the ACF group and 81 to the DCF group). The R0 resection rates for the ACF and DCF groups were equivalent (95.9% versus 96.2%, P = 0.93). The 2-year RFS and overall survival rates for DCF versus ACF were 64.1% versus 42.9% (hazard ratio 0.53, 95% confidence interval 0.33-0.83, P = 0.0057) and 78.6% versus 65.4% (P = 0.08), respectively. CONCLUSION: Compared with ACF, DCF chemotherapy was associated with prolonged RFS for patients with resectable advanced ESCC. Thus, DCF chemotherapy has potential as a standard neoadjuvant therapy for resectable ESCC. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN000004555/000004616).

Oral administration of bovine lactoferrin attenuates ultraviolet B-induced skin photodamage in hairless mice.

Lactoferrin (LF) is recognized as a host defensive glycoprotein, especially for newborn infants. The aim of this study was to investigate whether orally administered LF had protective activity against UV-induced skin damage in hairless mice. Transepidermal water loss and skin hydration were evaluated in nonirradiated mice, UVB-irradiated mice, and UVB-irradiated and LF-administered mice. Supplementation with LF (1,600 mg/kg per day) effectively suppressed the increase in transepidermal water loss, reduction in skin hydration, aberrant epidermal hyperplasia, and cell apoptosis induced by UV irradiation. Although no significant changes in superoxide dismutase-like activity or malondialdehyde levels were observed in the skin with both UV irradiation and LF administration, UV-stimulated IL-1ß levels in the skin were significantly suppressed by the administration of LF. Oral supplementation with LF has the potential to reduce IL-1ß levels and prevent UV-induced skin damage. Further studies are needed to elucidate the relationships between the antiinflammatory effects and skin protective function of LF.

CRTH2-dependent, STAT6-independent induction of cedar pollen dermatitis.

BACKGROUND: Airborne contact dermatitis to cedar pollen is a recently identified disease that generally affects individuals with cedar pollinosis of the nasal and/or ocular symptoms, as well as some patients with atopic dermatitis. OBJECTIVE: To elucidate the pathological mechanisms of cedar pollen dermatitis. METHODS: We established a mouse model of cedar pollen dermatitis by epicutaneous sensitization with Japanese cedar pollen antigen (Ag). RESULTS: Histologically, there was marked dermal cellular infiltrate, including eosinophils and mast cells, with epidermal thickening. The induction of dermatitis was accompanied by production of cedar pollen-specific IgE. In the lesional skin, IL-13, IL-18, eotaxin/chemokine (C-C motif) ligand (CCL) 11, regulated upon activation, normal T cell expressed and secreted/CCL5, macrophage-derived chemokine/CCL22 and thymus and activation-regulated chemokine/CCL17, but not IL-4 and IFN-gamma, were produced. Mast cell-deficient WBB6F1-W/W(v) mice failed to develop cedar pollen dermatitis, although regional lymph node cells proliferated in response to Cryptomeria japonica (Cry j) 1 and Cry j2 Ags in vitro. Surprisingly, the induction of dermatitis was independent of STAT6/IgE. In contrast, mice deficient in CRTH2, a receptor for prostaglandin D2 (PGD2), showed diminished inflammation. Consistent with this, ramatroban, a CRTH2 antagonist, significantly inhibited inflammatory cell infiltration. CONCLUSION: These data suggest that PGD2-CRTH2 signalling contributes to inflammation in cedar pollen dermatitis, and unlike cedar pollinosis of the nasal mucosa, STAT6 is not a therapeutic target for treatment.

Pharmacology and toxicology of Bupleurum root-containing Kampo medicines in clinical use.

Kampo (Japanese traditional herbal) medicines have been produced by combining multiple crude drugs, almost all of plant origin but with some of animal or mineral origin, and contain a great many substances. Their effect is a combination of the various interactions of the constituent substances, whether they are enhancing, synergistic or suppressive. Kampo medicine has an overall effect that is different from the combined effects of individual crude drugs, and several side effects such as anorexia, slight fever and nausea have been reported in the treatment of certain disorders and disease states with Kampo medicines. Among 210 medical formulations used in Japan, some relevant information on the clinical uses, pharmacology and toxicology of six manufactured Kampo medical formulations, Shosaikoto, Daisaikoto, Saikokeishito, Hochuekkito, Saibokuto and Saireito, containing Bupleurum root are reviewed. Studies of some potential interactions between Kampo medicine and western drugs are also considered.

Effects of short-term folic acid and/or riboflavin supplementation on serum folate and plasma total homocysteine concentrations in young Japanese male subjects.

OBJECTIVE: To investigate the effects of short-term folic acid and/or riboflavin supplementation on serum folate and plasma plasma total homocysteine (tHcy) concentrations in young Japanese male subjects. DESIGN: In a double blind, randomized controlled trial. INTERVENTION: Subjects were randomly assigned to one of four groups and received a placebo (control group), 800 microg/day folic acid (FA group), 8.4 mg/day riboflavin (R group), or both (FAR group) for 2 weeks. SETTING: Tokyo, Japan. SUBJECTS: In total, 32 healthy male volunteers aged 20-29 years. RESULTS: At the end of the 2 week supplementation period, the tHcy concentration decreased significantly in the FA group. Serum folate concentrations had increased between 2.7 and 2.0-fold in the FA and FAR groups, respectively, but the mean within-group changes in serum folate and plasma tHcy concentrations did not differ between these two groups. At the end of the study, alanine amino transferase was decreased in the R and FAR groups, while alanine amino transferase was increased in the FA group. CONCLUSION: Supplementation with folic acid, 800 microg/day, for 2 weeks, increased the serum and red blood cell folate concentrations and decreased the plasma tHcy concentrations in healthy young male subjects. Riboflavin supplementation may have blunted the effect of folic acid, which resulted in a diminished reduction of tHcy in our subjects.

[The efficacy of switch therapy in community-acquired pneumonia in Japan].

To evaluate the efficacy of Switch therapy for community-acquired pneumonia, we conducted a prospective randomized controlled study in thirty-two hospitalized patients. These cases corresponded to Fine's risk classes II to IV. Using a table of random numbers, sixteen patients were assigned to a Switch therapy group, and the other sixteen, to a clinical pathway group. Both groups initially received intravenous antimicrobials. Within the Switch therapy group, when all the patients were afebrile for more than sixteen hours, their intravenous antimicrobials were switched to oral, and the patients were discharged on the following day. For all patients in the clinical pathway group, the critical pathway was defined as an eight-day planned hospitalization, with a time-task matrix formatted for disease treatment, laboratory testing, physical examination, oxygen saturation monitoring, ambulation, diet, patient education and clinical outcome. Switch therapy reduced the period of intravenous antimicrobial administration from 7.6 days to 4.0 days (p < 0.0001). The period required to switch to oral antimicrobials decreased from 8.3 days to 4.8 days (p < 0.0001); hospital stay length, from 9.8 days to 6.5 days (p = 0.0001); and medical resource utilization, from 330, 373 to 227,768 Japanese yen (p = 0.0002). No patient from either group required readmission. In conclusion, Switch therapy was more efficient than management with a clinical pathway for mild to moderate community-acquired pneumonia in hospitalized patients.

[Relation between intraoperative salvaged blood transfusion and postoperative infection after cardiac surgery].

In cardiac surgery, several studies have shown bacterial contamination rates of intraoperative salvaged blood ranging from 12.7 to 96.8%. We evaluated the relation between intraoperative salvaged blood transfusion produced by the Cell Saver 5 device (Haemonetics Corp., Braintree, MA, USA) and postoperative infection determined by bacteriological study and the postoperative clinical course after cardiac surgery. Seven cases of cardiac surgery were investigated by bacteriological study. Although bacteria were cultured from all salvaged blood, no bacteria were cultured from the patients' blood 24 hours after salvaged blood infusion. Another 26 patients who underwent cardiac surgery, were divided into groups: group CS (n = 15) with salvaged blood transfusion after operation and group N (n = 11) without salvaged blood transfusion, and were evaluated in relation to the postoperative clinical course. There were no statistically significant differences between group CS and group N in the data of WBC, CRP and maximum body temperature. One case of deep sternal wound infection and 2 cases of local wound infection were observed in group CS, but none in group N (p = 0.18). These complications were treated by primary closure without muscle flaps. We conclude that salvaged blood autotransfusion was not related to postoperative infections in cardiac surgery.

A small dose of midazolam decreases the time to achieve hypnosis without delaying emergence during short-term propofol anesthesia.

STUDY OBJECTIVE: To evaluate the effect of a small dose of midazolam (10 microg kg(-1)) on induction and emergence during short-term propofol anesthesia and to investigate the effects of subsequent administration of flumazenil. DESIGN: Double-blinded, prospective, randomized study. SETTING: Operating room of a medical college hospital. PATIENTS: 30 male ASA physical status I and II patients (ages 51 to 75) scheduled for minor surgery under spinal anesthesia. INTERVENTIONS: Patients were randomly allocated to one of three groups: the placebo-propofol-placebo (PP) group, the midazolam-propofol-placebo (MP) group, or the midazolam-propofol-flumazenil (MF) group. After administering placebo or midazolam (10 microg kg(-1)), propofol 250 microg kg(-1) min(-1) was infused. Immediately after confirming that the patient was hypnotized, we terminated the propofol infusion and administered placebo or flumazenil (5 microg kg(-1)). MEASUREMENTS: The dose and the times required to achieve hypnosis (the first endpoint) and to emerge from anesthesia (the second endpoint). The plasma concentration at each endpoint was determined. MAIN RESULTS: Midazolam significantly decreased the dose and time needed to achieve hypnosis [PP vs. MP, 66 +/- 14 vs. 48 +/- 15 mg, 260 +/- 55 vs. 179 +/- 44 sec, respectively (mean +/- SD)]. Thus, the plasma concentration of propofol at hypnosis was significantly lower (PP vs. MP, 3.31 +/- 0.78 vs. 2.41 +/- 0.57 microg mL(-1)). The time to emerge from anesthesia was not prolonged by midazolam, and was further shortened by administration of flumazenil (PP, MP vs. MF, 237 +/- 77, 207 +/- 71 s vs. 126 +/- 56 sec, respectively). Flumazenil also reversed the reduction in propofol concentration induced by midazolam at emergence (PP, MP, and MF, 0.54 +/- 0.17, 0.37 +/- 0.15, and 0.59 +/- 0.22 microg mL(-1), respectively). CONCLUSIONS: Coadministration of 10 microg kg(-1)midazolam decreases the dose and time required to achieve hypnosis with propofol induction without delaying emergence from anesthesia. Additional administration of flumazenil further shortens the time to emerge from midazolam-propofol anesthesia.

Neurotrophic actions of novel compounds designed from cyclopentenone prostaglandins.

Previously we found that some cyclopentenone prostaglandin derivatives promoted neurite outgrowth from PC12 cells and dorsal root ganglia explants in the presence of nerve growth factor; and so we referred to them as neurite outgrowth-promoting prostaglandins (NEPPs). In this study, NEPPs protected HT22 cells against oxidative glutamate toxicity. NEPP6, one of the most effective promoters of neurite outgrowth in PC12 cells, protected the cells most potently among NEPPs 1--10. Several derivatives, NEPPs 11--19, were newly synthesized based on the chemical structure of NEPP6. NEPP11 had a more potent neuroprotective effect than NEPP6. NEPP11 also prevented the death of cortical neurons induced by various stimuli and reduced ischemic brain damage in mice. Biotinylated compounds of NEPPs were synthesized to investigate their cellular accumulation. NEPP6-biotin protected the cells and emitted potent signals from the cells. In contrast, biotinylated non-neuroprotective derivatives emitted much weaker signals. These results suggest that NEPPs are novel types of neurotrophic compounds characterized by their dual biological activities of promoting neurite outgrowth and preventing neuronal death and that their accumulation in the cells is closely associated with their neuroprotective actions.

Efficacy of a 14-day course of oral ciprofloxacin therapy for acute uncomplicated pyelonephritis.

This study aimed to evaluate the efficacy and safety of oral antibacterial treatment with fluoroquinilone for acute uncomplicated pyelonephritis Thirteen female patients with acute uncomplicated pyelonephritis were treated with oral fluoroquinilone (ciprofloxacin; CPFX). They received 200 mg of the drug three times a day while febrile (3-5 days). Once they become afebrile, the same dose of the drug, given twice a day, was given for another 9-11 days. The mean duration of the course of CPFX was 14 days. Symptoms were evaluated, and laboratory examinations, including urine culture and measurement of the minimal inhibitory concentration (MIC) of CPFX were conducted before treatment, and 3, 7, 14, 21, and/or 28 days after the initiation of the treatment. Of the 13 patients, only 5 needed to be hospitalized, and the period of hospitalization was only a few days. On the 14th day after the commencement of treatment, bacteriologic and clinical cure rates were 100%. Escherichia coli was the most common uropathogen, being isolated from the urine of 8 patients. No clinical relapse of the disease was found during a follow-up period of up to 4 weeks. The patients tolerated the drug well without developing any serious adverse effects. Oral antimicrobial chemotherapy with fluoroquinolone, given on an outpatient or short-term hospitalization basis, achieved satisfactory bacteriological and clinical outcomes in the treatment of acute uncomplicated pyelonephritis. This treatment regimen is indicated for patients with this disease who are not in a serious condition with complications such as shock.

Induction of apoptosis by Acanthopanax senticosus HARMS and its component, sesamin in human stomach cancer KATO III cells.

Antitumor effect of the stem bark of Acanthopanax senticosus HARMS (ASH) from Hokkaido (Japanese name: Ezoukogi) on human stomach cancer KATO III cells was investigated. The extract of the stem bark of ASH prepared with hot water was dissolved in distilled water and used for the assay of antitumor effect on the KATO III cells. The exposure of KATO III cells to ASH led to both growth inhibition and induction of apoptosis. Morphological change showing apoptotic bodies was observed in the cells treated with ASH. The fragmentation by ASH of DNA to oligonucleosomal-sized fragments that are characteristics of apoptosis was observed to be concentration- and time-dependent. We have investigated which component in ASH is effective on the induction of apoptosis. Among chlorogenic acid, syringaresinol di-o-beta-D glucoside, syringin, and sesamin, components of the n-butanol extract prepared from ASH, sesamin suppressed the growth and induced apoptosis in the cells. These findings suggest that growth inhibition by ASH results from the apoptosis induced by sesamin, a component of ASH.

Hematin polymerization assay as a high-throughput screen for identification of new antimalarial pharmacophores.

Hematin polymerization is a parasite-specific process that enables the detoxification of heme following its release in the lysosomal digestive vacuole during hemoglobin degradation, and represents both an essential and a unique pharmacological drug target. We have developed a high-throughput in vitro microassay of hematin polymerization based on the detection of (14)C-labeled hematin incorporated into polymeric hemozoin (malaria pigment). The assay uses 96-well filtration microplates and requires 12 h and a Wallac 1450 MicroBeta liquid scintillation counter. The robustness of the assay allowed the rapid screening and evaluation of more than 100, 000 compounds. Random screening was complemented by the development of a pharmacophore hypothesis using the "Catalyst" program and a large amount of data available on the inhibitory activity of a large library of 4-aminoquinolines. Using these methods, we identified "hit" compounds belonging to several chemical structural classes that had potential antimalarial activity. Follow-up evaluation of the antimalarial activity of these compounds in culture and in the Plasmodium berghei murine model further identified compounds with actual antimalarial activity. Of particular interest was a triarylcarbinol (Ro 06-9075) and a related benzophenone (Ro 22-8014) that showed oral activity in the murine model. These compounds are chemically accessible and could form the basis of a new antimalarial medicinal chemistry program.

[Negative-pressure pulmonary edema associated with transurethral resection syndrome].

We described a patient who had developed negative-pressure pulmonary edema associated with severe transurethral resection syndrome. A relatively healthy, 67-yr-old man (171 cm and 77 kg) with hypertrophic prostate was scheduled for transurethral resection of the prostate under spinal anesthesia. The patient was sedated with continuous propofol infusion because of his anxiety and wish of being asleep. Fifty minutes after starting the operation, electrolyte analysis revealed a decrease in serum Na+ concentration (116 mEq.l-1), and 10 mg of furosemide and hypertonic saline were administered. Thirty minutes later, the arterial oxygen saturation dropped suddenly and arterial blood gas analysis suggested marked pulmonary insufficiency (PaO2: 64 mmHg and PaCO2: 59.4 mmHg). The patient's trachea was intubated and endotracheal release of pinkish foamy sputum was observed. Chest X-ray showed severe lung edema. Massive absorption of the irrigation fluid might have decreased the electrolyte concentration (Na+: 101.0 mEq.l-1) and colloid oncotic pressure. No evidence of cardiac failure was observed immediately after the incidence of pulmonary edema with pulmonary catheter monitoring. The patient's airway was almost intact under spontaneous breathing, but augmented negative-pressure derived from intermittent snoring was considered to be sufficient to break hydrostatic balance of pulmonary capillary vessels and lead to severe pulmonary edema.

Isolation of a germin-like protein with manganese superoxide dismutase activity from cells of a moss, Barbula unguiculata.

A novel extracellular Mn-superoxide dismutase (SOD) was isolated from a moss, Barbula unguiculata. The SOD was a glycoprotein; the apparent molecular mass of its native form was 120 kDa, as estimated by gel filtration chromatography, and that of its monomer was 22,072 Da, as estimated by time of flight mass spectroscopy. The protein had manganese with a stoichiometry of 0.80 Mn/monomer. The cDNA clone for a gene encoding the extracellular Mn-SOD was isolated. Sequence analysis showed that it has a strong similarity to germin (oxalate oxidase) and germin-like proteins (GLPs) of several plant species and possesses all the characteristic features of members of the germin family. The clone encoding this extracellular Mn-SOD was therefore designated B. unguiculata GLP (BuGLP). BuGLP had no oxalate oxidase activity. In addition, the cDNA for a gene encoding the moss mitochondrial Mn-SOD was isolated. Its amino acid sequence had little similarity to that of BuGLP, even though a close similarity was observed among the mitochondrial Mn-SODs of various organisms. BuGLP was the first germin-like protein that was really demonstrated to be a metalloprotein with Mn-SOD activity but no oxalate oxidase activity.

[New hearing test for functional deafness--the procedure to estimate the genuine hearing threshold].

This report describes a new procedure for examining functional deafness with binaural sound stimulation. This new hearing test can estimate the genuine pure tone hearing threshold quantitatively at every frequency by using the ordinary audiometer. In the case of the nonorganic deafness, even if the hearing disorders are bilateral or hemilateral, we believe that measuring auditory threshold separately, causes the deterioration of the threshold. Therefore, this procedure is designed so that the subject may not be aware of testing the auditory acuity of each ear, and utilizes the response of the phantom sound image in the head by simultaneous binaural presentation of sound stimulation. Our strategy is based on the following facts. If the normal subject has the same pure tone threshold level in both ears, the phantom sound image is formed in the median plane of the head by the equal suprathreshold tone level presented simultaneously in each ear. In the case of a unilateral auditory disorder, the sound image is localized to the center of the head only when sound stimulation louder than the threshold level of affected ear is given to both ears at the same time. Simultaneous binaural sound stimulation at a lower level than the threshold of the affected ear forms a lateralized sound image to the unaffected ear in the head. For patients with bilaterally similar hearing loss, the sound image is not formed if the stimulation is less than the threshold level of the pure tone. The band noise in the phase of each frequency with 50 dB HL was given binaurally to 10 normal hearing subjects, and the localization of the sound image formation was examined. This experiment confirmed that around the occipital region of the median plane in all subjects. Furthermore, comparing the formation threshold of the median plane image with the pure tone auditory threshold, proved that there was no significant difference statistically in either value. As a next step, 15 patients with unilateral sensorineural deafness were examined with this technique and we knew that the median sound images would not be formed with stimulation less than the pure tone auditory threshold of the affected ear. For clinical application, patients were classified into two groups with unilateral (6) and bilateral (2) functional deafness, and examined. Midline sound images definitely were formed with the lower magnitude of sound than the pure tone threshold by hemilateral nonorganic deafness. The difference of the forming threshold of the median sound image and the average of pure tone hearing level of the affected ear were maximum 100 dB, minimum 35 dB, and mean 69.4 dB. Furthermore, the difference of the median image forming threshold and the average hearing level of the unaffected ear were maximum 35 dB, minimum 0 dB, and mean 15.4 dB. In bilateral disorders, the midline plane sound image was formed with the corresponding level of the pure tone value in one subject, though the other one was determined by the maneuver method because it did not form a midline sound image. In conclusion, this examination can be readily used to estimate the genuine hearing threshold of the functional deafness.

Prevention by methylprednisolone of increased circulating tumor necrosis factor-alpha levels and lung injury associated with systemic inflammatory response syndrome due to intraperitoneal hyperthermia.

UNLABELLED: We previously demonstrated that intraperitoneal hyperthermic perfusion (IPHP), which is performed clinically as a treatment for patients with advanced gastrointestinal cancer, can lead to increased serum tumor necrosis factor-alpha (TNF-alpha), systemic inflammatory response syndrome (SIRS), and acute lung injury. Glucocorticoids inhibit the production and actions of TNF-alpha. We investigated whether pretreatment with methylprednisolone (MPS) may modulate serum TNF-alpha and lung injury in patients subjected to IPHP. Serum TNF-alpha was not detected in the patients pretreated with MPS, whereas serum TNF-alpha increased in the control patients (45.7 +/- 8.3 pg/mL, mean +/- SEM) after IPHP. Postoperative lung injury scores were significantly lower in patients pretreated with MPS than in the control patients (P < 0.001). IMPLICATIONS: Pretreatment with methylprednisolone attenuates the increase in circulating tumor necrosis factor-alpha and prevents lung injury in this systemic inflammatory syndrome due to intraperitoneal hyperthermic perfusion.

A study of novel antiallergic agents with eosinophilic infiltration inhibiting action.

The antiallergic action of a series of novel mono-O-substituted trimethylhydroquinones was investigated. Among this series of the compounds, 4-[4-[4-(diphenylmethyl)-1-piperazinyl]butoxy]-2,3,6- trimethylphenol (compound 3) showed a potent antihistaminic action (pA2 = 7.11) and an antiasthmatic action (100 mg/kg. p.o) on sensitized guinea pigs. Moreover, this compound exhibited a strong eosinophilic infiltration inhibiting action on sensitized mice (100 mg/kg p.o.).