Subject(s)
Hypertension, Portal/complications , Hypertension, Pulmonary/complications , Autoimmunity , Humans , Hypertension, Portal/diagnosis , Hypertension, Portal/immunology , Hypertension, Portal/therapy , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/immunology , Hypertension, Pulmonary/therapy , Prevalence , Sex DistributionABSTRACT
Prematurely born infants with intraventricular hemorrhage (IVH) suffer significant morbidity and mortality, particularly those infants with high grade hemorrhage. The more premature infants have a higher incidence, experiencing more severe IVH. Early onset IVH is also likely to be severe and to progress to a higher grade. The etiology of intraventricular hemorrhages is clearly multifactorial, with differing sets of risk factors for early onset and later occurring hemorrhage. Prevention requires multilayered strategies, both prenatal and postnatal. These strategies are discussed in detail, highlighting unresolved controversies. Certain recommendations for prevention can be made. These include efforts to prevent preterm delivery, transfer of high risk mothers to tertiary care centers and antenatal maternal steroid use. Postnatally, the importance of optimal resuscitation and neonatal care practices is stressed, particularly those which minimize cerebral blood flow fluctuation. Postnatal indomethacin use should be considered in most infants. Further investigation of other strategies is necessary, including multicenter randomized trials to further evaluate antenatal pharmacologic agents, as well as the relative efficacy of different modes of delivery. The different risk factors for early onset versus later onset IVH must be more clearly delineated. Most importantly, any strategy must include sustained neurodevelopmental followup.
Subject(s)
Cerebral Hemorrhage/prevention & control , Infant, Premature , Adrenal Cortex Hormones/therapeutic use , Cerebral Hemorrhage/etiology , Delivery, Obstetric , Female , Humans , Indomethacin/therapeutic use , Infant, Newborn , Pregnancy , Risk Factors , Tocolytic Agents/therapeutic useABSTRACT
OBJECTIVE: To determine the impact of collagen shields on ulceration of rabbit corneas after alkali burn. METHODS: After a 60-second 2N sodium hydroxide burn to rabbit corneas, 24-hour collagen shields were placed on the corneas daily for 21 days; control corneas did not receive collagen shields. The extent of corneal ulceration was documented daily for 21 days by slit-lamp examination of treated and control eyes. Three separate studies were performed using collagen shields from two commercial sources. RESULTS: In the three studies, corneas in the collagen shield-treated eyes began to ulcerate sooner than those in the control group; the corneas in collagen shield-treated eyes also began to perforate sooner. At 21 days after alkali injury, the mean (+/- SE) corneal ulceration score in the collagen shield-treated rabbits was 4.1 +/- 0.17 (descemetocele formation) compared with 2.7 +/- 0.28 (midstromal ulceration) in controls. This difference was significant at P < .005. CONCLUSION: Collagen shield treatment results in marked acceleration of corneal ulceration and perforation after alkali injury.
Subject(s)
Biological Dressings/adverse effects , Burns, Chemical/etiology , Collagen/adverse effects , Corneal Ulcer/etiology , Eye Burns/chemically induced , Animals , Burns, Chemical/pathology , Corneal Ulcer/chemically induced , Corneal Ulcer/pathology , Eye Burns/pathology , Female , Male , Microscopy, Electron, Scanning , Rabbits , Sodium HydroxideSubject(s)
Burns, Chemical/drug therapy , Corneal Ulcer/prevention & control , Eye Burns/chemically induced , Keratitis/drug therapy , Metalloendopeptidases/antagonists & inhibitors , Pseudomonas Infections/drug therapy , Animals , Bacterial Proteins/antagonists & inhibitors , Burns, Chemical/complications , Corneal Ulcer/etiology , Drug Therapy, Combination , Eye Burns/complications , Eye Burns/drug therapy , Gentamicins/therapeutic use , Keratitis/complications , Keratitis/microbiology , Pseudomonas Infections/complications , Pseudomonas aeruginosa/enzymology , RabbitsABSTRACT
Pseudomonas aeruginosa elastase is a zinc metalloproteinase which is released during P. aeruginosa infections. Pseudomonas keratitis, which occurs following contact lens-induced corneal trauma, can lead to rapid, liquefactive necrosis of the cornea. This destruction has been attributed to the release of both host-derived enzymes and the bacterial products P. aeruginosa elastase, alkaline protease, exotoxin A, and lipopolysaccharide endotoxin. A synthetic metalloproteinase inhibitor, HSCH2 (DL)CH[CH2CH(CH3)2]CO-Phe-Ala-NH2, which we previously showed to be a potent inhibitor of corneal collagenase and alkali-induced corneal ulceration, was tested as a potential inhibitor of P. aeruginosa elastase. Inhibition constants (Kis) for the resolved diastereomers were determined with the chromogenic substrate furylacryloyl-glycyl-L-leucyl-L-alanine. One isomer had a Ki of 0.3 microM, while the other had a Ki of 0.4 microM. The more potent diastereomer was evaluated in vivo in experimentally induced Pseudomonas keratitis in rabbits. Following inoculation of one cornea of each rabbit, topical treatment with a 1 mM solution of the inhibitor significantly delayed the onset of corneal melting and perforation, as compared with the results for the control and gentamicin-treated groups. This protective effect suggests that the inhibitor may have a therapeutic application by delaying the progression of corneal destruction in Pseudomonas keratitis.
