Shock and acute organ dysfunction

Multiple trauma, hemorrhage, and sepsis may produce various kinds of shock, and such a host as shock could not be controlled and may easily fall into multiple organ dysfunction. Although those mechanisms on the pathogenesis of these sequential inflammatory responses have been clarified recently, the clinical outcome of such patients suffering from severe sepsis and multiple organ dysfunction is still very low. This inflammatory response against the insult shows a sequential manner; cardiovascular system failure, renal system failure, respiratory system failure, central nervous system failure, and finally, hepatic failure. However, the host response to the insult is a kind of defense against the invasion, and the clinical goal might be to stabilize hemodynamic system, metabolic system, and immunologic system. To achieve hemodynamic homeostasis, we use catecholamines and blood transfusion to improve the oxygen supply to important organs and enhance tissue repair. For metabolic homeostasis, early administration of hyperalimentation may be needed, either parenterally or enterally. Enteral feeding may also provided a route for bacterial translocation. To achieve immunologic homeostasis, prophylactic antibiotic administration and metabolic support may be required and should also protect against infection as a secondary invasion. This review explains these mechanisms in terms of the relationship between shock and organ dysfunction and the general features of clinical management.     

Excimer laser-induced hydroxyl radical formation and keratocyte death in vitro

PURPOSE: To characterize the type of reactive oxygen species (ROS) produced by excimer photoablation of aqueous solutions and to show the effects of ROS and antioxidants on corneal stromal cells in vitro. METHODS: Electron spin-resonance spectroscopy was performed using the spin-trapping agent 5,5-dimethyl-1-pyrroline N-oxide (DMPO) for the detection of the superoxide anion and the hydroxyl radical in an acellular DMPO solution irradiated with the excimer laser. Hydroxyl radicals were produced by the Fenton reaction in vitro by the mixture of hydrogen peroxide and ferrous iron (Fe2+), and the effects on cultured corneal fibroblasts were observed by fluorescent microscopy using the cell death marker, propidium iodide (PI) and TdT-mediated dUTP nick-end labeling (TUNEL). RESULTS: Excimer photoablation of a 1% DMPO solution produced a species-specific spin-trapping adduct for the hydroxyl radical ('OH), but not for the superoxide anion or other unidentified free radical. The signals were inhibited dose dependently by the hydroxyl radical scavenger dimethylsulfoxide (DMSO) and an L-ascorbic acid analogue, EPCK-1. The production of *OH in the supernatant of cultured rabbit corneal fibroblasts by the Fenton reaction caused an increase in PI (+) and TUNEL (+) cells by 90 minutes, which was significantly inhibited by the addition of DMSO. CONCLUSIONS: Hydroxyl radicals may be partly responsible for stromal fibroblast cell apoptosis after excimer photoablation.     

Morphology and barrier function of the corneal epithelium after penetrating keratoplasty: association with original diseases, tear function, and suture removal.

PURPOSE: To study changes in structure and barrier function of the corneal epithelium after penetrating keratoplasty. METHODS: Sixty-nine eyes of 56 patients undergoing penetrating keratoplasty were studied. Fifty-six age-matched normal eyes served as controls. Corneal epithelial structure was studied by using specular microscopy. Barrier function of the corneal epithelium was examined by slit-lamp fluorophotometry. Vital staining, tear function, and corneal sensitivity also were examined. RESULTS: Fluorescein and rose bengal staining scores, incidence of elongated cells, the mean epithelial area, and mean fluorescein uptake were significantly increased in postkeratoplasty eyes compared with controls. Original disease influenced the results of barrier function, where keratoconus revealed better function than bullous keratopathy or corneal scar. However, no such differences were noted in epithelial structure. Six eyes with absence of palisades of Vogt had revealed significantly increased epithelial area and fluorescein uptake. Removal of the running suture caused a decrease in elongated cells and epithelial cell area without significant changes in barrier function. CONCLUSION: Corneal epithelial structure was significantly impaired in postkeratoplasty eyes. Epithelial barrier function of postkeratoplasty eyes was influenced by original diseases. Removal of sutures improves epithelial structure but not barrier function.     

Geographic Clustering Patterns in Mortality from Biliary Tract Cancer in Japan

We calculated the standardized mortality ratios (SMRs) of biliary tract cancer (BTC) in Japan from 1981 to 1990 and statistically analyzed the results according to 333 Secondary Areas of Medical Care, as well as sex and subsite [gallbladder cancer (GBC) and extrahepatic bile duct cancer (BDC)], in order to examine geographic clustering patterns of BTC. In GBC in both sexes, the Secondary Areas of Medical Care with high SMRs were clustered in the eastern part of Japan. In BDC in both sexes, the Areas with high SMRs were clustered between the northern and eastern parts of Japan. In comparison with GBC, this clustering favored the northern part of Japan. In males, the clustering pattern in mortality from BTC was mainly due to the occurrence of BDC. In females, the clustering pattern in mortality from BTC reflected that of GBC. The clustering of BTC, especially GBC, seems to be related to the distribution of plains, basins, and rivers.     

Primary high-grade myofibroblastic sarcoma arising from the pericardium.

Primary pericardial sarcomas are very rare. A 62-year-old Japanese man presented with cardiac tamponade. Echocardiography, computed tomography and magnetic resonance imaging revealed massive pericardial effusion and a large tumor in the pericardial cavity, attached to the pericardium of the left ventricular posterolateral free wall. Surgical excision of the tumor was performed and histopathological and immunohistochemical examinations identified high-grade myofibroblastic sarcoma. Because of local recurrence soon after surgery, the patient received adjuvant chemotherapy, including doxorubicin and ifosfamide, and subsequent radiotherapy. As of 6 months after completing radiotherapy, the patient was alive and no disease progression or distant metastases were evident. This may be the first report of primary high-grade myofibroblastic sarcoma arising from the pericardium.     

Prostanoids in the Therapy of Glaucoma

Elevated intraocular pressure (IOP) is one of the most important risk factors for the development of glaucoma, which is a progressive optic neuropathy. Lowering IOP is currently the only therapeutic approach to the therapy of glaucoma. Since the use of pilocarpine eye drops for glaucoma treatment was reported in the late 1870s, academic researchers and pharmaceutical companies attempted to discover new drugs with more potent, prolonged, and safer IOP‐reducing effects. These persistent efforts finally paid off, and prostanoids with FP‐receptor agonist activity were found to be very potent IOP‐lowering agents. To date, three prostanoids (latanoprost, travoprost and bimatoprost) have been launched in many countries, and now a new FP‐receptor agonist, tafluprost, is entering clinical development. All of these prostanoids are superior to the β‐adrenoceptor antagonists in their IOP‐lowering efficacy, and no severe side effects have been reported in their long‐term clinical use. In addition, tafluprost may be expected to improve ocular blood flow. Hence, prostanoids currently occupy center stage among glaucoma medications. It cannot be denied that in terms of efficacy, safety, patient compliance, and medical economy prostanoids are currently the first‐line medicines among ocular antihypertensive drugs.     

Right and left ventricular volume characteristics in children with transposition of the great arteries after Mustard's procedure

With use of biplane cine-angiocardiograms, the measurements of right and left ventricular volume were determined in 11 children with transposition of the great arteries following Mustard's procedure. Right ventricular end-diastolic volume (RVEDV) ranged from 124 to 264 percent of the normal right ventricular volume with an average of 188 +/- 40 (SDM) percent, and left ventricular end-diastolic volume (LVEDV) ranged from 57 to 181 (122 +/- 43) percent of the normal (p less than 0.01, vs. RVEDV). Right ventricular ejection fraction (RVEF) ranged from 0.26 to 0.66 (0.42 +/- 0.11), and left ventricular ejection fraction (LVEF) ranged from 0.51 to 0.79 (0.66 +/- 0.09) (p less than 0.001, vs RVEF). Left ventriculography showed a deviation of the interventricular septum toward the left ventricle in patients with simple transposition of the great arteries not associated with left ventricular hypertension. The left to right ventricular systolic pressure ratio ranged from 0.22 to 1.02 (0.48 +/- 0.28), and the left to right ventricular end-diastolic volume ratio ranged from 0.43 to 1.00 (0.63 +/- 0.18). There was a high correlation between the left to right ventricular systolic pressure ratio and the left to right ventricular end-diastolic volume ration (r = 0.94, p less than 0.001). The left to right ventricular systolic pressure ratio also correlated well with the right ventricular ejection fraction (r = 0.90, p less than 0.001). Deviation of the interventricular septum was considered to result in a diminished ejection fraction of the right ventricle, in patients with simple transposition of the great arteries not associated with left ventricular hypertension, after Mustard's procedure.