Herpes keratitis.

Herpes simplex virus-1 (HSV-1) infects the majority of the world's population. These infections are often asymptomatic, but ocular HSV-1 infections cause multiple pathologies with perhaps the most destructive being herpes stromal keratitis (HSK). HSK lesions, which are immunoinflammatory in nature, can recur throughout life and often cause progressive corneal scaring resulting in visual impairment. Current treatment involves broad local immunosuppression with topical steroids along with antiviral coverage. Unfortunately, the immunopathologic mechanisms defined in animal models of HSK have not yet translated into improved therapy. Herein, we review the clinical epidemiology and pathology of the disease and summarize the large amount of basic research regarding the immunopathology of HSK. We examine the role of the innate and adaptive immune system in the clearance of virus and the destruction of the normal corneal architecture that is typical of HSK. Our goal is to define current knowledge of the pathogenic mechanisms and recurrent nature of HSK and identify areas that require further study.

Comparison of in vitro and in vivo efficiencies of a novel unit-dose liquid aerosol generator and a pressurized metered dose inhaler.

Gamma scintigraphic imaging was employed in 10 healthy volunteers to compare the total and regional lung deposition of aerosols generated by two delivery platforms that permitted microprocessor-controlled actuation at an optimal point during inhalation. An aqueous solution containing 99mTc-DTPA was used to assess the deposition of aerosols delivered by inhalation from two successive unit-dosage forms (44 microl volume) using a prototype of a novel liquid aerosol system (AERx Pulmonary Delivery System). This was compared with aerosol deposition after inhalation of two 50 microl puffs of a 99mTc-HMPAO-labeled solution formulation from a pressurized metered dose inhaler (MDI). The in vitro size characteristics of the radiolabeled aerosols were determined by cascade impaction. For the AERx system, the predicted lung delivery efficiency based on the product of emitted dose (60.8%, coefficient of variation (CV)=12%) and fine particle fraction (% by mass of aerosol particles <5.7 microm in diameter) was 53.3% (CV=13%). For the solution MDI, the emitted dose was 62.9% (CV=13%) and the predicted lung dose was 44. 9% (CV=15%). The AERx system demonstrated efficient and reproducible dosing characteristics in vivo. Of the dose loaded into the device, the mean percent reaching the lungs was 53.3% (CV=10%), with only 6. 9% located in the oropharynx/stomach. In contrast, the lung deposition from the solution MDI was significantly less (21.7%) and more variable (CV=31%), with 42.0% of the radiolabel detected in the oropharynx/stomach. Analysis of the regional deposition of the radioaerosol indicated a homogeneous pattern of deposition after delivery from the AERx system. A predominantly central pattern of distribution occurred after MDI delivery, where the pattern of deposition was biased towards a central zone depicting the conducting airways. The AERx system, in contrast to MDIs, seems highly suited to the delivery of systemically active agents via pulmonary administration.

Aerosol deposition in the human lung following administration from a microprocessor controlled pressurised metered dose inhaler.

BACKGROUND: Gamma scintigraphy was employed to assess the deposition of aerosols emitted from a pressurised metered dose inhaler (MDI) contained in a microprocessor controlled device (SmartMist), a system which analyses an inspiratory flow profile and automatically actuates the MDI when predefined conditions of flow rate and cumulative inspired volume coincide. METHODS: Micronised salbutamol particles contained in a commercial MDI (Ventolin) were labelled with 99m-technetium using a method validated by the determination of (1) aerosol size characteristics of the drug and radiotracer following actuation into an eight stage cascade impactor and (2) shot potencies of these non-volatile components as a function of actuation number. Using nine healthy volunteers in a randomised factorial interaction design the effect of inspiratory flow rate (slow, 30 l/min; medium, 90 l/min; fast, 270 l/min) combined with cumulative inspired volume (early, 300 ml; late, 3000 ml) was determined on total and regional aerosol lung deposition using the technique of gamma scintigraphy. RESULTS: The SmartMist firing at the medium/early setting (medium flow and early in the cumulative inspired volume) resulted in the highest lung deposition at 18.6 (1.42)%. The slow/early setting gave the second highest deposition at 14.1 (2.06)% with the fast/late setting resulting in the lowest (7.6 (1.15)%). Peripheral lung deposition obtained for the medium/early (9.1 (0.9)%) and slow/early (7.5 (1.06)%) settings were equivalent but higher than those obtained with the other treatments. This reflected the lower total lung deposition at these other settings as no difference in regional deposition, expressed as a volume corrected central zone:peripheral zone ratio, was apparent for all modes of inhalation studied. CONCLUSIONS: The SmartMist device allowed reproducible actuation of an MDI at a preprogrammed point during inspiration. The extent of aerosol deposition in the lung is affected by a change in firing point and is promoted by an inhaled flow rate of up to 90 l/min-that is, the slow and medium setting used in these studies.

Bicyclist and environmental factors associated with fatal bicycle-related trauma in Ontario.

OBJECTIVE: To identify bicyclist and environmental factors associated with fatal bicycle-related trauma in Ontario. DESIGN: Retrospective study. SETTING: Ontario. PARTICIPANTS: Information was extracted from the provincial coroner's reports on 212 people who had died of bicycle-related injuries in Ontario between 1986 and 1991. OUTCOME MEASURES: Age, sex and helmet use of the bicyclist, time and place of the event, type of bicyclist or motorist error(s) and use of alcohol by bicyclist or motorist. RESULTS: Only 32% of the deaths involved bicyclists under 15 years of age. The male-female ratio was 3.5. Over 75% of the cases involved head injury; however, only 8 (4%) of the bicyclists had been wearing a helmet. In 91% of the cases death occurred as the result of a bicycle-motor vehicle collision. Most (65%) of the deaths for which the time was known occurred between 4 pm and 8 am. Bicyclist error was the main cause of crash for 26 (79%) of the children less than 10 years old; it was also the main cause of crash among the bicyclists aged 10 to 19 years (43 [55%]) and those aged 45 years or more (15 [44%]). However, motorist error was the most common cause of collision in the group of cyclists 20 to 44 years of age (42 [63%]). Alcohol was detected in the blood of 7% of the bicyclists killed; alcohol had been consumed by 30% of the motorists who claimed not to have seen the cyclist. CONCLUSIONS: Bicycle-related deaths result from factors that are generally avoidable. Identifiable risk factors other than lack of helmet use suggest that additional research is required to determine the benefits of preventive interventions aimed at reducing the number of such deaths. Age-specific strategies appear warranted.