Prospective randomized controlled study on the effects of perioperative administration of a neutrophil elastase inhibitor to patients undergoing video-assisted thoracoscopic surgery for thoracic esophageal cancer.

Sivelestat sodium hydrate (Ono Pharmaceutical Co., Osaka, Japan) is a selective inhibitor of neutrophil elastase (NE) and is effective in reducing acute lung injury associated with systemic inflammatory response syndrome (SIRS). We conducted a prospective randomized controlled study to investigate the efficacy of perioperative administration of sivelestat sodium hydrate to prevent postoperative acute lung injury in patients undergoing thoracoscopic esophagectomy and radical lymphadenectomy. Twenty-two patients with thoracic esophageal cancer underwent video-assisted thoracoscopic esophagectomy with extended lymph node dissection in our institution between April 2007 and November 2008. Using a double-blinded method, these patients were randomly assigned to one of two groups preoperatively. The active treatment group received sivelestat sodium hydrate intravenously for 72 hours starting at the beginning of surgery (sivelestat-treated group; n= 11), while the other group received saline (control group; n= 11). All patients were given methylprednisolone immediately before surgery. Postoperative clinical course was compared between the two groups. Two patients (one in each group) were discontinued from the study during the postoperative period because of surgery-related complications. Of the remaining 20 patients, 2 patients who developed pneumonia within a week after surgery were excluded from some laboratory analyses, so data from 18 patients (9 patients in each group) were analyzed based on the arterial oxygen pressure/fraction of inspired oxygen ratio, white blood cell count, serum C-reactive protein level, plasma cytokine levels, plasma NE level, and markers of alveolar type II epithelial cells. In the current study, the incidence of postoperative morbidity did not differ between the two groups. The median duration of SIRS in the sivelestat-treated group was significantly shorter than that in the control group: 17 (range 9-36) hours versus 49 (15-60) hours, respectively (P= 0.009). Concerning the parameters used for the diagnosis of SIRS, the median heart rates on postoperative day (POD) 2 were significantly lower in the sivelestat-treated group than in the control group (P= 0.007). The median arterial oxygen pressure/fraction of inspired oxygen ratio of the sivelestat-treated group were significantly higher than those of the control group on POD 1 and POD 7 (POD 1: 372.0 [range 284.0-475.0] vs 322.5 [243.5-380.0], respectively, P= 0.040; POD 7: 377.2 [339.5-430.0] vs 357.6 [240.0-392.8], P= 0.031). Postoperative white blood cell counts, serum C-reactive protein levels, plasma interleukin-1beta, tumor necrosis factor-alpha levels, and plasma NE levels did not differ significantly between the two groups at any point during the postoperative course, nor did serum Krebs von den Lungen 6, surfactant protein-A, or surfactant protein-D levels, which were used as markers of alveolar type II epithelial cells to evaluate the severity of lung injury. Plasma interleukin-8 levels were significantly lower in the sivelestat-treated group than in the control group on POD 3 (P= 0.040). In conclusion, perioperative administration of sivelestat sodium hydrate (starting at the beginning of surgery) mitigated postoperative hypoxia, partially suppressed postoperative hypercytokinemia, shortened the duration of SIRS, and stabilized postoperative circulatory status after thoracoscopic esophagectomy.

Identification of stable RNA hairpins causing band compression in transcriptional sequencing and their elimination by use of inosine triphosphate.

To identify stable RNA secondary structure causing band compression, 30 lambda DNA clones and four cDNA clones (about 10 kb in total length) were sequenced using Transcriptional Sequencing, which is based on the phage RNA polymerase chain termination reaction with fluorescent 3' deoxynucleoside triphosphate, using the canonical set of rNTPs for the substrate. Electrophoresis was performed on acrylamide gel containing 7 M urea at 50 degrees C using ABI 377 DNA sequencer. A total of 159 band compressions were identified, and most compression sites seem to be due to hairpin structures. We also found that the presence of rITP in place of rGTP in the sequencing reaction can entirely eliminate all band compressions. The use of rITP gave a better peak uniformity and resolution in the sequencing gel in the case of lambda DNA than with c7rGTP, leading to improved accuracy in the sequence determination. Substitution of the base analog rITP for rGTP should be useful for accurate sequencing determination.

Expression and localization of angiogenic inhibitory factor, chondromodulin-I, in adult rat eye.

PURPOSE: To determine the role in the eye of chondromodulin (ChM)-I, which has been identified in cartilage as an angiogenic inhibitor, the expression and localization and a possible function of ChM-I were investigated. METHODS: Expression and localization of ChM-I in rat eyes were examined by RNase protection assay and in situ hybridization and by immunostaining, using an antibody against a synthetic peptide. The effect of recombinant ChM-I on tube morphogenesis of retinal endothelial cells was examined in culture. RESULTS: The rat ChM-I gene was determined to encode the open reading frame of 334 amino acid residues, and ChM-I mRNA was exclusively expressed in cartilage, eye, and cerebellum in rats. ChM-I mRNA expression was evident in the iris-ciliary body, retina, and scleral compartments, but not in other compartments of the eye. In situ hybridization revealed mRNA expression in the ganglion cells, inner nuclear layer cells, and pigment epithelium in the retina and in the nonpigment epithelium of the ciliary body. Immunoreactive ChM-I was present in these cells and also in the vitreous body. Western blot analysis detected an approximately 25-kDa band of ChM-I presumed as a secretory form in the aqueous humor and vitreous body and an approximately 37-kDa band as a precursor form in the retina. Recombinant human ChM-I inhibited tube morphogenesis of human retinal endothelial cells in vitro. CONCLUSIONS: These observations indicate a potential role for ChM-I in inhibition of angiogenesis in the rat eye.

Metachronous development of malignant Leydig cell tumor.

Leydig cell tumor (LCT), a rare testicular tumor, is malignant in only about 10% of the cases. We report the case of a patient with bilateral malignant LCTs that developed metachronously. After undergoing a right inguinal orchiectomy for a malignant LCT at the age of 43 years, the patient was given cisplatin-based chemotherapy for suspected para-aortic lymph node metastasis. Eighteen months after the right orchiectomy, examination of a left testicular biopsy specimen showed a malignant LCT and a left inguinal orchiectomy was performed. Histologically, the initial malignant LCT exhibited a highly pleomorphic appearance with mitotic figures (58/10 HPF), whereas the second malignant LCT showed fewer mitoses (2/10 HPF). The proliferating cell nuclear antigen (PCNA)-labelling index in these tumors also differed (right-sided tumor, 50%; left-sided tumor, 28%). These findings suggest that the malignant LCT in the left testis developed as a second primary rather than as a metastatic tumor. There have been no known similar cases, although three cases of malignant LCT with contralateral metastasis have been reported.

Hypercalcemia in children presenting with acute lymphoblastic leukemia.

Although hypercalcemia is a well-recognized complication in malignant disorders, neither the incidence and prognostic significance of hypercalcemia, nor the role of parathormone related peptide (PTHrP) in pediatric acute lymphoblastic leukemia (ALL) have been clarified. Of 83 newly diagnosed pediatric ALL patients with early pre-B cell phenotype treated at our hospital during the last 8 years, four patients were diagnosed as having hypercalcemia (> 14 mg/dl). In these 4 hypercalcemic ALL patients at onset, serum calcium levels ranged from 14.6 to 20.8 mg/dl (normal 7.4-9.0 mg/dl), and serum PTHrP levels were markedly elevated to 112-240 pmol/l (normal range: 17.6-61.2 pmol/l). Unlike patients with ordinary ALL in childhood, gastrointestinal symptoms (nausea, vomiting, abdominal pain) and skeletal symptoms (bone pain, gait disturbance) were the chief complaints. Because of these characteristic symptoms, bone marrow aspiration was carried out in two patients in an attempt to diagnose ALL before leukemic cells appeared in peripheral blood. Serum calcium levels were promptly normalized by induction chemotherapy. The four patients have been in complete remission from 35+ to 125+ months. Based on these results, the incidence of hypercalcemia in pediatric ALL patients with early pre-B cell phenotype at our institute is calculated to be about 4.8%. Gastrointestinal and skeletal problems are the characteristic initial symptoms, and hypercalcemia does not seem to be significant in the prognosis of these patients.

Contribution of endogenous prostaglandins to excitation of the myenteric plexus of guinea-pig ileum: are adrenergic factors involved?

The role of endogenous prostaglandins (PGs) in the nicotine-induced contraction and release of ACh was investigated in the isolated guinea-pig ileum. A low concentration of indomethacin (IND 2.8 microM) inhibited the contraction and ACh release induced by nicotine. These inhibitory effects of IND were reversed by PGE2 at concentrations which are thought to be released spontaneously. SC-19220, a PG receptors antagonist, also inhibited the contraction and ACh release induced by nicotine. Unlike the nicotine-induced release of ACh, the potassium-induced release of ACh was unaffected by IND and SC-19220. IND was as potent in inhibiting the responses to cholinergic nerve stimulation by nicotine after treatment of the preparations with antiadrenergic agents. It is concluded that the inhibitory effect of IND does not depend on the functional integrity of adrenergic neurons and that endogenous PGs contribute directly to the modulation of myenteric plexus excitability by nicotine.

Measurement of microcirculation in the optic nerve head by laser speckle flowgraphy and scanning laser Doppler flowmetry.

PURPOSE: To evaluate and compare blood flow measurements by laser speckle flowgraphy and scanning laser Doppler flowmetry in the optic nerve head of normal volunteers. METHODS: This prospective study included 60 eyes of 60 normal volunteers (50.0 years; range, 21 to 77 years). Measurements were taken at the temporal neuroretinal rim away from visible vessels. The square blur rate, a quantitative index of relative blood velocity, was measured by laser speckle flowgraphy. Using scanning laser Doppler flowmetry, volume, flow, and velocity were measured at the same neuroretinal rim locations. RESULTS: The average square blur rate, volume, flow, and velocity were 7.11 +/- 1.65, 7.74 +/- 3.19, 151.85 +/- 70.63, and 0.53 +/- 0. 23 arbitrary units, respectively (n = 60). Square blur rate correlated significantly with flow and velocity (r =.361, P =.005; r =.359, P =.005, respectively). However, there was no significant correlation between square blur rate and volume (r =.101, P =.441). Although square blur rate decreased significantly with increasing age (r = -.375, P =.003), volume, flow, or velocity showed no significant correlation with age (r = -.249, P =.054; r = -.166, P =. 205; r = -.143, P =.275, respectively). Square blur rate also decreased significantly with mean blood pressure (r = -.315, P =. 014), but volume, flow, or velocity showed no significant correlation with mean blood pressure (r = -.159, P =.225; r = -.059, P =.654; r = -.043, P =.742, respectively). CONCLUSION: We found only a weak correlation between the blood flow indexes, as measured by laser speckle flowgraphy and scanning laser Doppler flowmetry because of basic differences in the principles of measurement.

Measurement of microcirculation in optic nerve head by laser speckle flowgraphy in normal volunteers.

PURPOSE: To report blood flow in the optic nerve head between the right and left eyes or the superior and inferior neuroretinal rims in normal volunteers using laser speckle flowgraphy. METHODS: This prospective study included 120 eyes of 60 normal volunteers (mean age, 50.0 +/- 16.9 years; range, 21 to 77 years). The square blur rate was measured by laser speckle flowgraphy (Kyushu Institute of Technology, Iizuka, Japan). The sequence of eye measurements was randomized. In each eye, measurements were taken at the neuroretinal rim away from visible vessels. Linear regression analysis, paired two-tailed t test, and two-way analysis of variance were used for statistical analysis. P values less than.05 were accepted as statistically significant. RESULTS: There was a significant correlation in square blur rate between the right and left eyes (r = 0.587, P <.001). Square blur rate in the superior temporal neuroretinal rim significantly correlated with that in the inferior temporal neuroretinal rim in each of the right (r = 0.546, P <.001) and left (r = 0.465, P <.001) eyes. Square blur rate in the right eye was higher than that in the left eye (P =.049). Square blur rate in the superior neuroretinal rim was higher than that in the inferior neuroretinal rim in both the right (P =.035) and left (P =. 005) eyes. CONCLUSION: There were statistically significant differences of optic nerve head blood flow in normal volunteers using laser speckle flowgraphy between the right and left eyes and between the superior and inferior temporal neuroretinal rims. These normal data can be used for understanding physiological ocular hemodynamics.

A light and electron microscopic study of calcitonin gene-related peptide in the rat caudate putamen.

Calcitonin gene-related peptide (CGRP)-like immunoreactive (CGRP-IR) structures have been studied in the rat caudate putamen using avidin-biotin peroxidase immunohistochemistry. Immunoreactivity was found in the axons of this nucleus but not in the perikarya. CGRP-IR fibers were most densely concentrated along the ventral border and in the caudal portion of the rat caudate putamen. CGRP-IR fibers were sparsely distributed throughout the rest of this nucleus. Almost all immunoreactive boutons which contained small clear vesicles had formed asymmetrical synapses. Postsynaptic targets included dendritic spines and shafts. Asymmetrical synapses in the caudate putamen are supposed to be extrinsic in origin. These observations, together with the results of other investigations, suggest that CGRP-IR boutons form synapses with spiny striatal neurons, which, most likely, are medium-sized spiny projecting neurons. Moreover, evidence indicates that these boutons are of extrinsic origin.

Measurement of retinal nerve fibre layer by scanning laser polarimetry and high pass resolution perimetry in normal tension glaucoma with relatively high or low intraocular pressure.

AIMS: To determine whether any differences may exist in the relation between the neural capacity as determined by high pass resolution perimetry and the thickness of the retinal nerve fibre layer (RNFL) in patients having normal tension glaucoma (NTG) with a relatively high intraocular pressure (IOP) between 16 and 21 mm Hg (HNTG) v those with a lower IOP below 15 mm Hg (LNTG). METHODS: Scanning laser polarimetry and high pass resolution perimetry were performed in 20 eyes of 20 patients with HNTG and 21 eyes of 21 patients with LNTG. The correlation between total and regional thickness of the peripapillary RNFL and the corresponding total and regional neural capacity with linear regression analysis were evaluated. RESULTS: Overall, although the total RNFL thickness was not significantly correlated with the total neural capacity, the RNFL thickness in each of the superior and inferior quadrants was significantly correlated with the corresponding regional neural capacity (r = 0.44, p = 0.0045; r = 0.39, p = 0.0126 for each). The RNFL thickness in each of the superior and inferior quadrants in the HNTG group was significantly correlated with the corresponding regional neural capacity (r = 0.52, p = 0.0196; r = 0.49, p = 0.0286 for each). No significant correlation between neural capacity and the RNFL thickness was observed either globally or regionally in the LNTG group. CONCLUSION: The degree of the correlation between neural capacity as determined by high pass resolution perimetry and thickness of the RNFL as measured by scanning laser polarimetry appeared to differ in NTG patients with an IOP higher than 15 mm Hg v those with a lower IOP.

Computed tomographic diagnosis of strangulated obstruction.

A case of strangulated obstruction with computed tomographic appearance is reported. CT may be useful for the demonstration of the strangulated loop in a patient with obstructive symptoms and a soft tissue mass in the pelvis shown on plain films of the abdomen.

Spontaneous ruptured middle colic artery aneurysm with concurrent renal cell carcinoma.

We present the first reported case of spontaneous ruptured middle colic artery aneurysm in a patient who has concurrent hypervascular tumor which has a potential for rupturing. A 68-year-old Japanese man was admitted with abdominal pain and hypervascular renal tumor which developed in the subcapsular cortex and protruded outward. The next morning after admission, anemia rapidly progressed and severe abdominal pain developed. Emergency laparotomy was performed for a preliminary diagnosis of ruptured hypervascular renal tumor. However, the renal tumor was not ruptured but a ruptured middle colic artery aneurysm was found. The aneurysm measured 3.0 x 2.0 cm in greatest diameter and was resected. Three weeks later, nephrectomy for hypervascular renal tumor was electively performed. Histologically, the tumor was clear cell carcinoma. In the present case, the diagnosis of ruptured middle colic artery was extremely difficult.

Relationship between age and the thickness of the retinal nerve fiber layer in normal subjects.

PURPOSE: To determine it there are any age-dependent changes in the thickness of the retinal nerve fiber layer (RNFL) in the peripapillary area. METHODS: Sixty normal volunteers (31 men, 29 women) (120 eyes) whose ages ranged from 23-75 years (mean 48.4 years) participated in this study. The thickness of the RNFL was determined using a scanning laser polarimeter along the peripapillary area with a 1.75 disc diameter and along another ring 0.8 mm away from the disc margin. RESULTS: The thickness of the RNFL was not significantly correlated with age in either of the two ring areas. However, the RNFL thickness ratio of total/nasal area decreased significantly with increase in age in both rings. There was an increase in the difference of RNFL thickness between the right and left eyes of the same individual with aging, in both rings. CONCLUSIONS: It was suggested that the RNFL thickness determined along both rings demonstrated almost identically the relationship between age and RNFL thickness in normal subjects.

Chemical control of Haematobia irritans with 0.5% topical ivermectin solution in cattle.

A field trial was conducted to evaluate the efficacy of a topical formulation of ivermectin administered at the dose of 500 micrograms/kg against horn flies (Haematobia irritans) in cattle. Eighty-eight cattle in four herds naturally exposed to horn flies were used in the trial. Replicates were formed of two herds. Within replicates, one herd was randomly allocated to the untreated control and the other to the ivermectin treatment group. Horn fly counts were taken on the treatment day (Day 0) and on Days 7, 14, 21, 28, and 35 post-treatment. There were no horn flies on any cattle in the treatment group, whereas all the control cattle were continuously infested by horn flies on each examination day.

[Clinical experience of norfloxacin in urinary tract infection].

Norfloxacin (NFLX) was administered to outpatients and inpatients with urinary tract infections at our department. Clinical efficacy and safety were evaluated in 50 patients by the criteria for evaluation of clinical efficacy of antimicrobial agents on urinary tract infection. Overall clinical efficacy for 17 cases with acute simple cystitis was excellent in 13 cases, moderate in 4 cases with an effectiveness rate of 100%. The overall clinical efficacy for 33 cases with chronic complicated UTI was excellent in 18 cases, moderate in 6 cases and poor in 9 cases with an effectiveness rate of 73%. The eradication rate of 21 strains from acute simple cystitis patients was 100%. Forty four out of 60 strains from chronic complicated UTI patients were eradicated and the eradication rate was 73%. Neither subjective nor objective adverse reactions were observed in 50 patients. Abnormal changes in laboratory tests were found in 8 patients, but were probably not related to NFLX administration. Judging from these results, NFLX is considered to be an effective and safe antibacterial for the treatment of UTI.

[Implant operation of penile inflatable prosthesis for a patient with erectile impotence due to radical cystectomy: a case report].

The hydraulically inflatable penile prosthesis consists of an inflate-deflate pump, a storage reservoir and paired cylinders and it is able to provided a more physiologically functional penis. We report our surgical experience of implant of an inflatable penile prosthesis for postoperative impotence. The patient was a 51-year-old male with impotence, who had received radical cystectomy and ilial conduit formation for transitional cell carcinoma of the bladder (G3, pT3NoMo.) 9 months earlier. There was nothing particular except for the postoperative status on physical, laboratory and X-ray examinations. He was diagnosed to have organic impotence (vasculogenic) by sexual functional tests. Auto-injection of the corpus cavernosum with papaverine HCl was attempted but an erection was not induced by the injection. So, implant operation of an inflatable penile prosthesis was performed by the lower abdominal approach. His postoperative course was uneventable and practice to deflate and inflate the cylinders was started at 2 weeks after the operation and he was able to have sexual intercourse at 5 weeks after the surgery. Now (3 months after the operation), he can have sexual intercourse with an orgasm but without ejaculation and he and his wife are both satisfied with the postoperative status.

[Double primary malignant neoplasm of renal cell carcinoma and stomach cancer: report of two cases].

Two cases of double primary malignant neoplasm of renal cell carcinoma and gastric cancer are presented. Case 1 was a 59-year-old woman with right renal cell carcinoma (granular cell subtype) and gastric cancer (poorly differentiated adenocarcinoma). Case 2 was a 72-year-old man with left renal cell carcinoma (clear cell carcinoma) and gastric cancer (tubular adenocarcinoma). In both cases, the occult blood reactions of stool was strong and clear gastrointestinal symptoms developed. In these 2 cases of synchronous double cancer, gastrectomy following nephrectomy was performed in the same operation.

[A case of a combined aortectomy with dissection of recurrent paraaortic lymph nodes of sigmoid colon cancer].

A combined aortectomy was performed on a patient with recurrence of sigmoid colon cancer in the paraaortic lymph nodes. The 48-year-old woman was found to have tumor recurrence in the lymph nodes in the area between the aortic bifurcation and the paraaortic area, accompanied by left hydronephrosis, four years after surgery for sigmoid colon cancer (H0, P0, ss, n3, stage IIIb). No metastasis to distant areas was detected at that time. The woman thus underwent a reoperation. Intraoperatively, the aortic bifurcation and the lymph nodes were seen as a mass. The mass involved the left common iliac vein and the left ureter, as well. Therefore, we resected the area from the aortic bifurcation to the bilateral common iliac arteries, the left common iliac vein, the left ureter and the left kidney en bloc, and replaced them with a Y-shaped graft. One year after the reoperation, a tumor metastasis to the liver was detected, and a partial hepatectomy was performed. At present, the patient is being managed at our outpatient clinic. The results suggest that extended resection, involving the aorta as well, is sometimes useful when dealing with tumor recurrence in the paraaortic lymph nodes, unaccompanied by blood-borne metastasis.

[Open heart surgery for removal of secondary cardiac tumors].

Recent remarkable development of the non-invasive diagnostic apparatus such as two dimensional echocardiography, computed tomography and RI angiography improves early diagnosis for secondary cardiac tumors and promotes surgical treatments for them. Five cases of secondary intracardiac tumors underwent open heart surgery using cardiopulmonary bypass with successful removal. Although a case of direct invasion of a malignant thymoma into the pericardium, RA and SVC was lost at ICU after surgery because of massive hemorrhage followed by LOS, another 4 cases, i.e., a 27 year-old female with implantation of LA myxoma into the RA and RV, a case with intracavitary extension of leiomyosarcoma of the IVC, a case of intravenous extension of the uterine leiomyomatosis through the IVC to the pulmonary artery and a case of intravenous extension of chondrosarcoma of the left fibula to the heart are alive actively. Open heart surgery has become acceptable treatment for cases with secondary intracavitary cardiac tumors in order to rescue emergency cases with circulatory obstruction by the tumor mass, to make sure a pathological diagnosis of unknown origin and to promote further chemotherapy and/or radiation therapy after surgery. Our surgical results may support these active treatments for secondary cardiac tumors.

Decontamination of outdoor school swimming pools in Fukushima after the nuclear accident in March 2011.

Because of radioactive fallout resulting from the Fukushima Daiichi Nuclear Power Plant (NPP) accident, water discharge from many outdoor swimming pools in Fukushima was suspended out of concern that radiocesium in the pool water would flow into farmlands. The Japan Atomic Energy Agency has reviewed the existing flocculation method for decontaminating pool water and established a practical decontamination method by demonstrating the process at eight pools in Fukushima. In this method, zeolite powder and a flocculant are used for capturing radiocesium present in pool water. The supernatant is discharged if the radiocesium concentration is less than the targeted level. The radioactive residue is collected and stored in a temporary storage space. Radioactivity concentration in water is measured with a NaI(Tl) or Ge detector installed near the pool. The demonstration results showed that the pool water in which the radiocesium concentration was more than a few hundred Bq L was readily purified by the method, and the radiocesium concentration was reduced to less than 100 Bq L. The ambient dose rates around the temporary storage space were slightly elevated; however, the total increase was up to 30% of the background dose rates when the residue was shielded with sandbags.