Injury induced by chemical warfare agents: characterization and treatment of ocular tissues exposed to nitrogen mustard.
(33/274)
PURPOSE: Mustard agents are highly toxic and abundant warfare chemicals, primarily affecting ocular tissues, with no specific treatment antidote. The purpose of the present study was to examine the efficacy of novel metallocomplexes, known to inhibit the formation of highly reactive free radicals, to reduce ocular injury induced by nitrogen mustard (NM). METHODS: One eye in each of 72 rabbits was exposed to 1% to 2% NM. Topical treatment with eye drops of a metallocomplex--either zinc- or gallium-desferrioxamine (Zn/DFO and Ga/DFO)--was compared with treatment with saline, zinc (chloride), or DFO alone. Examiners masked to the treatment groups assessed the extent of ocular injury and the response to treatment using clinical, histologic, and biochemical criteria. RESULTS: Exposure to NM followed by administration of carrier alone (saline) caused severe and long-lasting injury to ocular anterior segment structures. Treatment with either Zn/DFO or Ga/DFO yielded marked protection (52%-64%), including faster healing of corneal epithelial erosions, less scarring and neovascularization, decreased inflammation in the anterior chamber, better maintenance of intraocular pressure, and less severe changes in the iris and lens. These were also associated with better preservation of systemic antioxidant status. Zinc or DFO alone afforded lower levels of protection. No toxic effects of these complexes were observed. CONCLUSIONS: It is suggested that Zn/DFO or Ga/DFO, by virtue of their enhanced ability to infiltrate cells and inhibit transition metal-dependent formation of free radicals through the combined push-pull mechanism, be considered as a basis for treatment of mustard injuries. (+info)
Predictors of esophageal stricture in children with unintentional ingestion of caustic agents.
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BACKGROUND: Prediction of the severity of esophageal injury following ingestion of a caustic substance is a challenging problem for clinicians. It was hoped that risk factors for the early prediction of esophageal stricture in such patients could be identified in this study. METHODS: This study comprises an evaluation of 32 children with esophageal injury due to ingestion of caustic materials. Patients' signs and symptoms as well as laboratory data including leukocyte counts and C-reactive protein level were reviewed. RESULTS: Patients who presented with a greater number of symptoms and signs were inclined to have more severe esophageal injury and stricture. The frequency of symptoms and signs in patients with serious esophageal injury was higher than that in patients with low-grade injury. Patients with severe injury were more significantly associated with the occurrence of stricture. The characteristic of caustic ingestion was associated with esophageal stricture, but not esophageal injury. There was no statistically significant difference in leukocyte counts relative to severity of esophageal injury. The mean of leukocyte counts of patients with esophageal stricture was close to that of patients without esophageal stricture. There was also no statistically significant difference in C-reactive protein values between the 2 groups of patients. CONCLUSIONS: Leukocyte counts and C-reactive protein are not useful parameters for predicting the severity of esophageal injury and occurrence of stricture following injury to the esophagus by caustic materials. Alkali ingestion more probably leads to esophageal stricture than acid ingestion. After caustic ingestion, the presence of a greater number of symptoms and signs suggests a more-severe injury, which necessitates more-aggressive management. (+info)
Ascorbate for alkali burns to the eye.
(35/274)
A short cut review was carried out to establish whether ascobate drops are useful in the management of alkalis burns to the eyes. Altogether 33 papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this best paper are tabulated. A clinical bottom line is stated. (+info)
Treatment of alkali-injured rabbit corneas with a synthetic inhibitor of matrix metalloproteinases.
(36/274)
Healing of corneal alkali injuries remains a severe clinical challenge. The authors evaluated the effect of a new synthetic inhibitor of matrix metalloproteinases (GM6001 or N-[2(R)-2-(hydroxamido carbonylmethyl)-4-methylpentanoyl]-L-tryptophane methylamide) on preventing ulceration of rabbit corneas after alkali injury. Topical treatment of corneas with severe alkali injuries with 400 micrograms/ml or 40 micrograms/ml GM6001 alone prevented ulceration for 28 days, although 8 of 10 corneas treated with vehicle perforated. Corneas treated with 4 micrograms/ml GM6001 had midstromal depth ulcers. Corneas treated with 400 micrograms/ml of GM6001 contained very few inflammatory cells and had significantly reduced vessel ingrowth compared with vehicle-treated corneas. Epithelial regeneration after moderate alkali injuries also was investigated. Persistent epithelial defects developed 4 days after moderate alkali injury in rabbit corneas treated with vehicle and progressively increased to an average of 20% of the original 6 mm diameter wound by 27 days after moderate alkali injury. By contrast, epithelial regeneration was complete and persisted for 21 days for corneas treated with a formulation containing GM6001 (400 micrograms/ml), epidermal growth factor (10 micrograms/ml), fibronectin (500 micrograms/ml), and aprotinin (400 micrograms/ml). Sporadic punctate staining developed in 20% of the corneas treated with the combination of agents between days 21-28 after moderate alkali injury. These results demonstrate that topical application of GM6001 prevented corneal ulceration after severe alkali injury and that a combination containing GM6001, epidermal growth factor, fibronectin, and aprotinin promoted stable regeneration of corneal epithelium after moderate alkali injury. (+info)
Acute and long term respiratory damage following inhalation of ammonia.
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A lifelong non-smoker who was the victim of a massive accidental exposure to anhydrous ammonia gas was followed up for 10 years. In the acute phase the patient presented with severe tracheobronchitis and respiratory failure, caused by very severe burns of the respiratory mucosa. After some improvement he was left with severe and fixed airways obstruction. Isotope studies of mucociliary clearance, computed tomography, and bronchography showed mild bronchiectasis. It is concluded that acute exposure to high concentrations of ammonia may lead to acute respiratory injury but also to long term impairment of respiratory function. (+info)
Altered KSPG expression by keratocytes following corneal injury.
(38/274)
PURPOSE: Keratocytes synthesize keratan-sulfate proteoglycans (KSPG), lumican and keratocan, to develop and maintain proper collagen interfibrillar spacing and fibril diameter characteristics of the transparent cornea. The purposes of this study are to compare the expression patterns of KSPGs and keratin 12 (K12) respectively by corneal keratocytes and epithelial cells after three different types of injuries; partial and total epithelial debridement and alkali burn. METHODS: Corneas of 8-12 week old C57Bl/6J or FVBN mice were wounded by partial epithelial (2 mm in diameter) and total epithelial debridement, and alkali burn (0.1 M NaOH, 30 s) and were allowed to heal for various periods of time, from 1 to 84 days. The corneas were then subjected to light microscopy, in situ and Northern hybridization and RT-PCR for examining the expression of K12 and KSPG in the corneal epithelium and stroma, respectively. Immunohistochemistry with anti-alpha-smooth muscle actin (alpha-SMA) was used to identify myofibroblasts in the stroma of injured cornea. RESULTS: In 2-3 days, partial epithelial denuded corneas were resurfaced by corneal epithelium positive for K12, and stromal edema caused by debridement disappeared. Total epithelial debridement wounded corneas were resurfaced by conjunctival epithelial cells in 2 weeks. Stromal edema in the total epithelial debridement corneas began to subside after 6 weeks. Corneal epithelial cells resurfaced alkali burned corneas within 3-5 days. In situ and Northern hybridization showed a decrease in keratocan and lumican expression at 6 weeks and increased at 12 weeks post-injury in all wound types. Alpha-SMA positive myofibroblasts in the cornea were detected via immunostaining at the time point when KSPG expression was lowest, 6 weeks post-injury. CONCLUSIONS: The results suggest keratocan and lumican are down-regulated during wound healing at 6 weeks and returned to higher levels at 12 weeks post-injury; implicating that the cells repopulating the injured corneal stroma regained the characteristic function of keratocytes independent of the wound types. However, complete epithelial removal results in irreversible loss of K12 expression. (+info)
Stepwise surgical approach for in vivo expansion of epithelial stem cells to treating severe acute chemical burns with total limbal deficiency.
(39/274)
To describe the clinical outcome of a new surgical treatment for the acute stages of severe corneal burn injury and its complications, a prospective study of five acute corneal burn patients with severe limbal damage was performed. Amniotic membrane transplantation (AMT) and conjunctival limbal autograft (CLAU) was performed at the acute stage of corneal burn injury to reconstruct the damaged ocular surface (step I). Three to six months later, the opaque central part of the amniotic membrane containing in vivo grown corneal stem cells were removed and retransplanted to the defect created after the removal of pseudopterygium (step II). All injured eyes were successfully treated, but in one eye with marked stromal lysis, three-layered AMT and penetrating keratoplasty with retransplantation of in vivo grown corneal stem cells was performed. In the former cases, visual acuity was greatly improved more than three lines (ranging from 3 to 12 lines). In short, retransplantation of in vivo grown corneal stem cells after AMT and CLAU is a recommendable modality for restoring a stable corneal epithelium of a severely burned ocular surface in the acute stage and can be considered a preventative measure for avoiding late onset complications. (+info)
Transhiatal esophageal resection for corrosive injury.
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OBJECTIVES: To analyze the feasibility and safety of transhiatal approach for resection of corrosively scarred esophagus. BACKGROUND SUMMARY DATA: The unrelenting corrosive strictures of esophagus merit esophageal substitution. Because of the risk of complications in the retained esophagus, such as malignancy, mucocele, gastroesophageal reflux, and bleeding, esophageal resection is deemed necessary. Transthoracic approach for esophageal resection is considered safe. The safety and feasibility of transhiatal resection of the esophagus is not established in corrosive injury of the esophagus. PATIENTS AND METHODS: Transhiatal approach was used for resection of the scarred esophagus for all patients between January 1986 and December 2001. The intraoperative complications, indications for adding thoracotomy, and postoperative outcome were studied in 51 patients. Follow-up period varied from minimum of 6 months to 15 years. RESULTS: Esophageal resection was achieved in 49 of 51 patients whereas thoracotomy was added in 2 patients. In 1 of the patients tracheal injury occurred whereas in other patient there were dense adhesions between tracheal membrane and esophagus. Gastric tube was used for esophageal substitution in 40 (78.4%) patients whereas colon was transplanted in 11 (21.6%) patients. Colon was used only when stomach was not available. One patient (1.9%) had tracheal membrane injury whereas 4 patients (7.8%) had recurrent laryngeal nerve palsy. One patient each had thoracic duct injury and intrathoracic gastric tube leak. There was no operative mortality. Anastomotic complications like leak were present in 19.6% and stricture in 58.8% patients. All the patients were able to resume their normal duties and swallow normal food within 6 months of the surgery. CONCLUSION: One-stage transhiatal esophageal resection and reconstruction could be safely used for the extirpation of scarred esophagus. Use of gastric conduit was technically simple, quicker, and offered good functional outcome. Postoperative anastomotic stricture amenable to dilatations was the commonest complication. (+info)