Endoscopic injection sclerotherapy with ligation versus endoscopic injection sclerotherapy alone in the management of esophageal varices: a prospective randomized trial.

BACKGROUND/AIMS: Endoscopic injection sclerotherapy with ligation is a technique by which endoscopic injection sclerotherapy is first carried out for a target esophageal varix using an endoscope equipped with a device for endoscopic variceal ligation, and subsequently, endoscopic variceal ligation is performed for the varix together with the injection site of the sclerosing agent. The aim of this prospective, randomized trial was to compare endoscopic injection sclerotherapy with ligation with endoscopic injection sclerotherapy techniques in utility for patients with esophageal varices. METHODOLOGY: Twenty-four patients with esophageal varices who were to undergo either an elective treatment of bleeding esophageal varices or a prophylactic treatment of non-bleeding esophageal varices underwent endoscopic injection sclerotherapy with ligation (n = 12) or without ligation (n = 12). The patients were followed for a mean of 19.9 +/- 8.1 months in the endoscopic injection sclerotherapy with ligation (EISL) group and 19.5 +/- 5.4 months in the Endoscopic injection sclerotherapy (EIS) group. RESULTS: The red color sign disappeared in 10 patients in the EISL group and 3 in the EIS group (P = 0.004) after initial treatment. The length of time required for initial treatment was 16.3 +/- 4.7 min for the EISL group and 27.2 +/- 6.2 min for the EIS group (P = 0.0003). For treatment-related complications, no significant difference was noted between the 2 groups and no serious complication were noted in the 2 groups. The total quantity of ethanolamine oleate used to attain the endpoint was 17.3 +/- 7.9 mL for the EISL group and 25.2 +/- 9.7 mL for the EIS group (P < 0.05). The cumulative non-relapse rate for 2 years following attainment of the endpoint [F1, RC(-)] was 81.5% for the EISL group and 47.5% for the EIS group, producing no significant difference between the 2 groups. The cumulative non-bleeding and survival rates were 100% in the 2 groups. CONCLUSIONS: Endoscopic injection sclerotherapy with ligation is more useful for esophageal varices than endoscopic injection sclerotherapy alone.

Low stray ELF magnetic field exposure system for in vitro study.

An exposure facility for wide application to cell exposure to an ELF (extremely low frequency) magnetic field was developed. It is suitable for conducting experiments under a high-intensity, variable-frequency magnetic field, on the biological effects of the ELF magnetic field in an in vitro study. The exposure system consists of Merritt's 4-square coil as a basic component to generate the required magnetic field intensity of 10 mT at 50 Hz with spatial field uniformity less than +/-3% in a 400 mm cube. Concentric compensation coils are adopted to eliminate the effects of stray fields on sham (control) samples in the vicinity of the exposure system. The uniformity of the magnetic field in the exposure coil, the increase in the power supply capacity due to the existence of compensation coils, and the stray field estimation were investigated carefully. After fabricating the system, performance tests were carried out and all the characteristics were found to be satisfactory. In addition, the ideal configuration for a concentric coil system was proposed.

Linearly and circularly polarized, 50 Hz magnetic fields did not alter intracellular calcium in rat immune cells.

This study was conducted to determine if exposure to 50 Hz magnetic field (MF) affects intracellular calcium ([Ca2+]i). We employed flow cytometry for real-time detection of possible changes in [Ca2+]i in a large number of cells. A solenoid coil for vertical MF exposure and a multiple-loop square-coil for horizontal MF were utilized. In the laboratory, background 50 Hz MF was less than 0.08 microT when all necessary equipment was powered. Rat thymocytes were exposed to 0.1 mT horizontal or vertical field, or to 0.14 mT circularly polarized field for 30 min; the effects of consecutive exposures to vertical and horizontal MFs, or vice versa, for 20 min each also were examined. In addition, intact thymocytes or lectin-activated thymocytes, splenocytes and peripheral blood lymphocytes were exposed to the 5 mT vertical field for 30 min. In all these experiments, no alteration in [Ca2+]i was evident. As a positive control, a calcium ionophore always was added to the medium following MF exposure to verify that the cells were capable of increasing [Ca2+]i and the system would record the response. The data indicate that MF exposure had no effect on [Ca2+]i under any of the conditions examined.

Endoscopic management of gastric varices using a detachable snare and simultaneous endoscopic sclerotherapy and O-ring ligation.

BACKGROUND: Cyanoacrylate injection is highly effective and is regarded as the treatment of choice in bleeding gastric varices in Europe, but intravenous injection of cyanoacrylate is not allowed in the USA and Japan because it may cause embolisms in other organs. Accordingly, we developed a new endoscopic combined treatment of endoscopic management of gastric varices using a detachable snare (EVLs) and simultaneous endoscopic sclerotherapy and O-ring ligation (EISL) (i.e. EVLs + EISL), and we prospectively evaluated its efficacy and safety. METHODS: Gastric varices were ligated with the loop of a detachable snare that opened to a diameter of 4 cm (EVLs). Then the residual varices around the ligated portion were sclerosed by ethanolamine oleate and the injected vessel was ligated using a pneumo-activated EVL device (EISL). The EVLs + EISL was performed in 35 patients: on an emergency basis in eight patients, on an elective basis in six patients and as primary prophylaxis in 21 patients. Liver function was classified as Child-Pugh class A in 12 patients, class B in 12 patients and class C in 11 patients. RESULTS: Endoscopic disappearance of gastric varices was obtained in 97.1% of the patients and they regressed in all patients. Haemostasis was achieved in all eight emergency cases. The 2-year cumulative non-recurrence rate was 85%, the 2-year cumulative non-bleeding rate was 92% and the 2-year cumulative survival was 80%. No patients died of bleeding from gastric varices. There were no serious short-term complications, such as haemorrhage, gastro-oesophageal perforation, ileus, or renal impairment. CONCLUSION: Combined EVLs + EISL appears to be a useful treatment for gastric varices due to its safety and good clinical outcome.

Immunocytochemical features of lens after cataract tissue--signalling molecules (growth factors, cytokines, other signalling molecules), cytoskeleton proteins, cellular and extracellular matrix proteins.

UNLABELLED: We examined the immunocytochemical features of after cataract tissue and cataractous lens epithelium prior to cataract surgery and at the time of surgery. METHODS: This study included 23 cases. Antibodies against the following antigens were used: epidermal growth factor (EGF), EGF receptor (EGF-R), fibroblast growth factor (FGF), FGF receptor (FGF-R), transforming growth factor (TGF)-beta, TGF-beta receptor II (TGF-beta -RII), insulin-like growth factor (IGF)II, platelet derived growth factor (PDGF)-AB, interleukin (IL)-6, IL-1 receptor II, tumor necrosis factor (TNF)-alpha, tissue plasminogen activator (TPA), prostaglandin (PG) E2, plasminogen activator inhibitor (PAI)-1, alpha smooth muscle actin (alpha-SMA), keratin, vimentin, myosin, fibronectin, laminin, types I, II, III, IV, V and VI collagen (Col), and lens epithelial cells (LECs). RESULTS: The following substances were present in posterior and anterior capsular fibrosis of after cataract: EGF, EGF-R, FGF, FGF-R, TGF-beta, TGF-beta-RII, IGF-II, PDGF-AB, IL-6, IL-1RII, TNF-alpha, PGE2, PAI-1, alpha-SMA, keratin, fibronectin, laminin, Type I col, Type II to VI col and LECs. Elschnig's pearls of after cataract expressed FGF-R, TNF-alpha, laminin and LECs. Soemmering's ring of after cataract tissue expressed EGF, FGF, FGF-R, IL-1RII, TPA, PAl-1, keratin and LECs. The following substances were present in cataractous lens epithelium prior to cataract surgery: EGF, EGF-R, FGF, FGF-R, TGF-beta-RII, IL-1-RII, TNF-alpha, PAI-1, keratin, laminin and LECs. The following substances were present in the lens epithelium of anterior capsules collected at the time of cataract surgery: EGF, EGF-R, FGF, FGF-R, TGF-beta, TGF-beta-RII, IGF-II, IL-6, IL-1-RII, TNF-alpha, PGE2, keratin, fibronectin, laminin, Type IV Col and LECs. CONCLUSIONS: These results prove that many kinds of signalling molecules and proteins exist in the process of after cataract formation.

Injection sclerotherapy for gastric varices using N-butyl-2-cyanoacrylate and ethanolamine oleate.

BACKGROUND/AIMS: Tissue adhesive agents, such as the cyanoacrylates, have been used as an alternative to conventional sclerotherapy to treat gastric varices, but the long-term efficacy of this approach has not been determined. We evaluated the efficacy and long-term outcome of injection sclerotherapy with n-butyl-2-cyanoacrylate and ethanolamine oleate in 16 patients with gastric varices. METHODOLOGY: We evaluated the effect of injection sclerotherapy in 16 Japanese patients with gastric varices. Injection sclerotherapy was performed on an emergency basis in 6 patients, an elective basis in 5 patients, and as prophylaxis in 5 patients. RESULTS: No bleeding was observed in the 7 patients in whom gastric varices disappeared during the 51 month follow-up period. The non-bleeding rate after treatment was significantly higher in this group than in the 9 patients in whom gastric varices did not disappear (p<0.05). Acute bleeding was stopped in 5 (83.3%) of 6 patients. The single failure was a patient in whom the sclerosant could not be injected into the gastric varices. No serious complications, such as emboli in other organs, were observed. CONCLUSION: The results suggest that this therapy is a safe and useful treatment for gastric varices and that the goal of injection sclerotherapy should be the disappearance of gastric varices.

[Immunohistochemical studies on factors involved in after cataract].

In this study, lenses of autopsy eyeballs, anterior capsules including lens epithelium taken during operation for cortical cataract, after cataract tissue obtained at the time of operation, and Elschnig's pearles and Soemmerring's ring from autopsy eye-balls were examined for a variety of factors, such as growth factors, cytokines, bioactive substance factors, cytoskeleton proteins and extracellular matrices by immunocytohistochemistry. Preoperative lens epithelium expressed epidermal growth factor (EGF), EGF-receptor (R), fibroblast growth factor (FGF), FGF-R, interleukin (IL)-1-RII, tumor necrosis factor-alpha (TNF-alpha), plasminogen activator inhibitor type-1 (PAI-1), keratin and laminine. In addition to the above factors, opacified fibrous capsule in after cataract expressed transforming growth factor-beta (TGF-beta), insulin-like growth factor-II (IGF-II), platelet derived growth factor-AB (PDGF-AB), IL-6, prostaglandin-E2 (PG-E2), alpha smooth muscle actin, fibronectin, and I and III to VI type collagen. Elschnig's pearls expressed FGF-R, TNF-alpha, and laminin. Soemmerring's ring expressed EGF, FGF, FGF-R, IL-1-RII, keratin, tissue-PA, and PAI-1.

Endoscopic ultrasonography and endoscopy for staging depth of invasion in early gastric cancer: a pilot study.

BACKGROUND: We compared the accuracy of endoscopic ultrasonography (EUS) for staging depth of invasion of early gastric cancer with that of conventional endoscopy. PATIENTS AND METHODS: We assessed the depth of invasion of 108 lesions (104 patients) using EUS with a thin 20 MHz probe and compared the results with those of conventional endoscopy and of histologic examination of endoscopically or surgically resected specimens. RESULTS: The overall accuracy rates for staging depth of invasion for conventional endoscopy and EUS were 72.2% and 64.8%, respectively. Lesions that were classified as limited to the mucosa on both conventional endoscopy and EUS were very likely (92.2%) to be limited to the mucosa on histologic examination. The rates for understaging and overstaging were 16.7% and 11.1%, respectively, for conventional endoscopy; and 7.4% and 24.1%, respectively, for EUS. The highest rate for understaging based on conventional endoscopy occurred for lesions in the gastric body (including cardia, 23.9%). CONCLUSIONS: EUS appears to be useful in combination with conventional endoscopy for staging depth of invasion of early gastric cancer. In particular, the two techniques in tandem may accurately predict that a lesion is limited to the mucosa, and EUS may be useful to overcome the potential for understaging by conventional endoscopy, particularly in the gastric body.

Therapeutic results of endoscopic variceal ligation for acute bleeding of oesophageal and gastric varices.

Endoscopic variceal ligation (EVL) using 'O' rings is widely accepted as a treatment of oesophageal varices that is at least as effective as endoscopic injection sclerotherapy but which produces fewer complications. Endoscopic variceal ligation using detachable snares has attracted attention as a safe and easy method of endoscopic treatment for gastric varices. Nineteen patients with acute bleeding from oesophageal or gastric varices were treated in the present study. Of these, 14 patients were treated with EVL using 'O' rings and five patients were treated with EVL using detachable snares and the treatment results were evaluated. Haemostasis was achieved in all patients. No serious complications of the procedures were observed. However, recurrences and rebleeding were observed in some patients during the maximum follow-up period of 24 months. Endoscopic variceal ligation using 'O' rings and detachable snares is useful for achieving haemostasis in cases of acute bleeding from oesophageal or gastric varices. However, additional endoscopic sclerotherapy may be needed to eliminate the variceal feeding vessels to further improve the long-term prognosis of these patients.

Effects of mucin ophthalmic solution on epithelial wound healing in rabbit cornea.

To test the hypothesis that a mucin ophthalmic solution could accelerate the healing of corneal epithelium, we conducted a study in rabbits using an ophthalmic solution containing mucin extracted from bovine submaxillary gland. The corneas of rabbits were abraded with a razor blade in the central portion over an area demarcated with a 7-mm trephine. Mucin-containing eye drops were instilled into the right eye 4 times a day for 3 days, and the vehicle was instilled into the left eye. After enucleation, the eyes were observed by scanning and transmission electron microscopy as well as light microscopy. Mucin-containing eye drops were shown to reduce the epithelial defect area more rapidly than the vehicle. Thus, the eye drops accelerated corneal epithelial wound healing.

Endoscopic ultrasonography of superficial esophageal cancers using a thin ultrasound probe system equipped with switchable radial and linear scanning modes.

BACKGROUND: Detailed information on the depth of invasion of superficial esophageal cancer is required for endoscopic mucosal resection. As a pretherapeutic diagnostic procedure, endoscopic ultrasonography using conventional 7.5 MHz systems has been ineffective at providing sufficient details. A newly developed, thin ultrasound probe system provides both radial and linear scanning for evaluation of superficial esophageal cancer. METHODS: Endoscopic ultrasonography was performed in 16 patients using a switchable probe driven at 20 MHz. Seventeen lesions of superficial esophageal cancer were evaluated for depth of invasion to discriminate mucosal from submucosal penetration. RESULTS: The overall accuracy of staging was 64.7%. In all six errors, mucosal cancers were overstaged as submucosal invasion. The diagnostic accuracy was 80% when the muscularis mucosae was visualized. CONCLUSION: A 20 MHz linear-radial switchable probe is a useful new method in the staging of superficial esophageal cancer.

Use of bifemelane hydrochloride in improving and maintaining the visual field of patients with glaucoma.

We investigated the change of visual fields in 40 patients with primary or secondary glaucoma. No limitations were placed on the type of angular glaucoma (ie, open or closed). The intraocular pressure of the patients had been controlled at < 20 mm Hg for 2 years before the study, and patients with normal-tension glaucoma also were included. We evaluated the effect of 48 months of treatment with bifemelane hydrochloride, 150 mg/d in three divided doses, on 20 patients with glaucoma. The control group included 20 glaucoma patients whose intraocular pressure had been controlled at < 20 mm Hg for 2 years before the study by the instillation or oral administration of an intraocular hypotensive agent. They had not received any oral agent, such as a cerebral circulation metabolism activator. Results showed that the visual field was improved in 14 (70%) of 20 patients who received bifemelane hydrochloride, whereas the visual field was improved in 4 (20%) of 20 patients in the control group. More patients in the bifemelane hydrochloride group had improved visual fields than in the control group; differences between groups were significant. In addition, an evaluation of the visual field with the use of the Kosaki and Inoue classification showed improvement in all patients in stages IIa to V. We conclude that this drug is useful for maintaining and improving the disturbed visual field of patients in whom the intraocular pressure can be maintained at < 20 mm Hg and in patients who can tolerate 150 mg/d in three separate doses.

The utilization of a biological adhesive for wound treatment: comparison of suture, self-sealing sutureless and cyanoacrylate closure in the tensile strength test.

UNLABELLED: We produced a measurement apparatus for testing the tensile strength of wounds during cataract surgery, and tested the tensile strength of treated wounds including wounds sutured with various methods, non-sutured and wounds treated with various bio-tissue adhesives. METHODS: In cataract surgery on white rabbits eyes, a corneoscleral incision 5 mm in length was made 2.5 mm from the limbus corneae, and entry into the anterior chamber was obtained 0.5 mm to the clear cornea. After treatment for closure, the corneoscleral piece was subjected to the tensile strength test. RESULTS: The tensile strengths just after surgery were (1) 0 gf/mm2 after self-sealing sutureless closure; (2) 114 gf/mm2 after vertical suture closure (one stitch with 10-0 nylon); (3) 125 gf/mm2 after horizontal suture closure (one stitch with 10-0 nylon); (4) 143 gf/mm2 after infinity suture closure (with 10-0 nylon); (5) 112 gf/mm2 after fibrin glue (Beriplast P) application (instilled on the surface of scleral incision); (6) 121 gf/mm2 after fibrin glue application (glued on corneoscleral wound); (7) 131 gf/mm2 after cyanoacrylate closure (instilled on the surface of scleral incision); (8) 139 gf/mm2 after cyanoacrylate closure (glued on corneoscleral wound). The respective strengths at four days after surgery were: (1) 86; (2) 131; (3) 137; (4) 175; (5) 109; (6) 43; (7) 138; and (8) 108 gf/mm2. At 28 days after surgery, the respective strengths were (1) 164; (2) 167; (3) 184; (4) 209; (5) 322; (6) 195; (7) 251; and (8) 175 gf/mm2. CONCLUSION: The use of fibrin glue in treatment of a wound in cataract surgery is beneficial in assisting this treatment.

Abducent nerve paralysis during interferon alpha-2a therapy in a case of chronic active hepatitis C.

A 59-year-old woman with chronic active hepatitis C was treated with recombinant human interferon alpha-2a. After three days of administration, the patient complained of diplopia with dizziness and head heaviness. Ophthalmic examinations revealed a disturbance of the movement of left eye ball to the outer side without any other neurological signs. The diplopia, which was diagnosed as abducent nerve paralysis, improved rapidly and reversed at about 6 weeks after discontinuation of interferon and during infusion of hydrocortisone. To our knowledge, this is the first report of abducent nerve paralysis associated with alpha-2a interferon.

Horizontal or vertical 50-Hz, 1-microT magnetic fields have no effect on pineal gland or plasma melatonin concentration of albino rats.

Three experiments were carried out on male Wistar-King rats to determine if 6 weeks of exposure to horizontally- or vertically-oriented 1-microT, 50-Hz magnetic fields suppresses melatonin content in plasma and pineal gland, as does 6 weeks of exposure to circularly-polarized, 50-Hz, 1-microT magnetic fields. In each experiment, a concurrent sham-exposed control group was exposed to a stray field of 0.02 microT. In addition, a separate control experiment was completed between the horizontal and vertical field experiments in which cage-controls were housed in the exposure facility for 6 weeks without activation of the magnetic field coils. Subjects were sacrificed at 12:00 or at 24:00 h for collection of plasma and pineal gland; melatonin was determined by radioimmunoassay. In contrast to the results of experiments with rotating-vector magnetic fields, there were no significant differences among 1-microT, 0.02-microT and control groups in melatonin concentration of pineal gland or plasma.

Recovery of nocturnal melatonin concentration takes place within one week following cessation of 50 Hz circularly polarized magnetic field exposure for six weeks.

In our earlier paper [Kato et al. (1993): Bioelectromagnetics 14:97-106], melatonin concentration in pineal gland and blood was reported to be suppressed after exposure to a circularly polarized 50 Hz magnetic field for 6 weeks. In the present series of experiments, we investigated the time course of recovery after cessation of the exposure. Rats were exposed to a circularly polarized 50 Hz magnetic field at 1 microT for 6 weeks, and the melatonin concentration of blood of separate groups was determined at the end of the exposure and at 1 week and 4 weeks following cessation of exposure. Nocturnal melatonin concentration was reduced (P < 0.05) after 6 weeks of exposure. Melatonin concentration at 1 week following cessation of exposure was normal, and no further change was observed 4 weeks later.

Circularly polarized, sinusoidal, 50 Hz magnetic field exposure does not influence plasma testosterone levels of rats.

We exposed rats to circularly polarized 50 Hz magnetic fields to determine if plasma testosterone concentration was affected. Previous experiments indicate that magnetic fields suppress the nighttime rise in melatonin, suggesting that other neuroendocrine changes might occur as well. Male Wistar-King rats were exposed almost continuously for 6 weeks to magnetic flux densities of 1, 5, or 50 microT. Blood samples were obtained by decapitation at 12:00 h and 24:00 h. Plasma testosterone concentration showed a significant day-night difference, with a higher level at 12:00 h when studied in July and December, but night difference, with a higher level at 12:00 h when studied in July and December, but the day-night difference disappeared when concentrations were studied in April. In three experiments, magnetic field exposure had no statistically significant effect on plasma testosterone levels compared with the sham-exposed groups. These findings indicate that 6 weeks of nearly continuous exposure to circularly polarized, 50 Hz magnetic fields did not change plasma testosterone concentration in rats.

Circularly polarized 50-Hz magnetic field exposure reduces pineal gland and blood melatonin concentrations of Long-Evans rats.

In order to determine if pigmented rats also exhibit melatonin suppression like that described for albino rats exposed to circularly polarized, 50-Hz, 1-muT magnetic fields for 6 weeks, two experiments were conducted with Long-Evans rats. The field-exposed experimental group received circularly polarized, 50-Hz, 1-muT magnetic fields for 6 weeks, the concurrent sham-exposed control group was exposed to the stray field of 0.02 muT. In addition, prior to the exposure experiment, two cage-control groups were placed in the facility for 6 weeks without activation of the 50-Hz magnetic field generation apparatus. Rats were sacrificed at 12.00 and at 24.00 h for collection of plasma and pineal gland: melatonin was determined by radioimmunoassay. Significant reductions of plasma and pineal gland melatonin contents were observed at 0.02 muT as compared to the control values, and a further reduction was observed at 1 muT. As do albino rats, pigmented rats rats also exhibit melatonin suppression when exposed to time-varying magnetic fields.

Effect of magnetic field on pineal gland volume and pinealocyte size in the rat.

Light microscopic observations on the superficial pineal gland of Wistar-King rats were made to examine whether or not pineal volume and pinealocyte size, expressed as nuclear density, at daytime or nighttime are affected by long-term exposure to 50 Hz rotating magnetic field (MF) at 5.0 microT. Determinations of pineal volume and pinealocyte size were repeated twice (April and October) during the year. Size of pinealocytes in MF-exposed and sham-exposed rats exhibited, in addition to the difference between peripheral and central regions, regional differences in a proximodistal direction; pinealocytes in the distal and middle-peripheral regions were usually larger than those in the proximal and middle-central regions at daytime or nighttime. In October, distal and proximal pinealocytes showed significant day-night changes in size in sham-exposed rats, but not in MF-exposed animals. The situations in the two groups were almost reversed in April. Significant day-night differences were scarcely found in pinealocyte size in the middle region in the two groups. Throughout the study, pineal volume and pinealocyte size in each region were generally the same between MF-exposed and sham-exposed rats at daytime or nighttime. The results suggest that pinealocytes in the distal and proximal regions, but not those in the middle region, are affected by MF-exposure; day-night differences in sizes of distal and proximal pinealocytes appear in April and disappear in October under the influence of MF. MF may exert an effect on mechanisms controlling day-night rhythms of pinealocyte size in the rat.

50-Hz magnetic field exposure system for small animals.

The design, construction, and results of evaluation of an animal-exposure system for the study of biological effects of extremely low frequency (ELF) magnetic fields are described. The system uses a square coil arrangement based on a modification of the Helmholtz coil. Due to the cubic configuration of this exposure system, horizontal and vertical magnetic fields as high as 0.3 mT can be generated. Circularly polarized magnetic fields can also be generated by changing the current and phase difference between two sets of coils. Tests were made for uniformity of the magnetic field, stray fields, sham-exposure ratio of stray field, changes of temperature and humidity, light intensity and distribution inside the animal-housing space, and noise due to air-conditioning equipment. Variation of the magnetic field was less than 2% inside the animal housing. The stray-field level inside the sham-exposure system is less than 2% of experimental exposure levels. The system can be used for simultaneous exposure of 48 rats (2 to a cage) or 96 mice (4 to a cage).