Ablation smoothness as a function of excimer laser delivery system

OBJECTIVE: To quantitatively study and compare the ablation profiles of three kinds of excimer laser delivery systems to identify which technology provides the smoothest ablation profile. SETTING: Three private practices, one in Canada and two in the United States. METHODS: Excimer laser myopic ablations were performed on poly(methyl methacrylate) (PMMA) test blanks in 3.00 diopter increments using a 5 mm optical zone with three kinds of excimer laser delivery systems: (1) iris diaphragm without beam-homogenizing technology (ExciMed, Summit Technologies, Inc.); (2) iris diaphragm with beam homogenizer (20/20, VISX, Inc.); (3) galvanometric scanning (Mini-Excimer, LaserSight, Inc.). We used a scanning white-light interferometer (NewView 100, Zygo Corp.) to study three measures of surface smoothness: peak to valley, root mean square average deviation height (RMS), and the arithmetic average deviation from the center line of the data. RESULTS: Using RMS as a measure of surface smoothness in an optical system, the galvanometric scanning delivery system produced ablations approximately three times smoother than the iris diaphragm with beam homogenizer (P = .01), which in turn produced ablations about twice as smooth as the iris diaphragm without beam homogenizer (P = .03). CONCLUSIONS: Galvanometric scanning delivery systems provide a significantly smoother ablation profile than iris-diaphragm (variable aperture) systems.     

Risk factors for the development of chronic obstructive pulmonary disease

Cigarette smoking clearly has been shown to be the major environmental risk factor predisposing to the development of COPD. Occupational exposures to dust and fumes, air pollution, passive smoke exposure, childhood respiratory infections, and diet may also contribute. Airway hyperresponsiveness is a risk factor for the development of decline in FEV1, but its role in the development of COPD remains uncertain. Alpha1-antitrypsin deficiency is an important genetic risk factor for COPD in the small minority of COPD patients who inherit this deficiency. Other genetic factors are likely involved but have not yet been identified. Elucidation of additional genetic risk factors may provide useful insights into the pathogenesis of COPD. Potential interactions between the various environmental and genetic risk factors may be extremely important in determining the variable development of COPD.     

Immunogenicity of an inactivated hepatitis A vaccine in healthy children: two years' follow-up

To investigate the long-term immunogenicity of an inactivated hepatitis A vaccine in children, 100 healthy children, aged between 1 and 7 years old and all lacking the antibody to hepatitis A (HA) virus, were enrolled in this trial. They received 3 doses of strain HM 175 HA vaccine with 360 enzyme-linked immunosorbent assay (ELISA) units at 0, 1 and 6 months, respectively. Blood sampling for antibody and aminotransferases was performed 7 days before, then 1, 6, 7, 12, and 24 months after the first dose. The titers of antibody to HA virus were tested by radioimmunoassay and ELISA methods. All subjects became ELISA seropositive at Month 6 after two doses of vaccine. Except for one boy, 99 remained seropositive at Month 24, with a geometric mean titer of 1,148 mIU/ml. Antibody titers for females were significantly higher than those for males throughout the follow-up period. It was concluded that the inactivated HA vaccine used in the present trial was immunogenic and safe in children below seven years old. The vaccine-induced antibody persisted for at least two years in 99% of the vaccinees.     

Open-channel block of N-methyl-D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity

Excessive activation of NMDA receptors is thought to mediate the calcium-dependent neurotoxicity associated with hypoxic-ischemic brain injury, trauma, epilepsy, and several neurodegenerative diseases. For this reason, various NMDA antagonists have been investigated for their therapeutic potential in these diseases, but heretofore none have proven to be both effective and safe. In the present study, memantine, an adamantane derivative similar to the antiviral drug amantadine, is shown to block the channels activated by NMDA receptor stimulation. From whole-cell and single-channel recording experiments, the mechanism of action of memantine is deduced to be open-channel block, similar to MK-801; however, unlike MK-801, memantine is well tolerated clinically. Compared to MK-801, memantine's safety may be related to its faster kinetics of action with rapid blocking and unblocking rates at low micromolar concentrations. Furthermore, at these levels memantine is an uncompetitive antagonist and should theoretically allow near-normal physiological NMDA activity throughout the brain even in the face of pathologically high focal concentrations of glutamate. These pharmacological properties confer upon memantine a therapeutic advantage against NMDA receptor-mediated neurotoxicity with few side effects compared with other organic NMDA open-channel blockers. Moreover, memantine is increasingly effective against escalating levels of glutamate, such as those observed during a stroke. Low micromolar concentrations of memantine, levels known to be tolerated by patients receiving the drug for the treatment of Parkinson's disease, prevent NMDA receptor-mediated neurotoxicity in cultures of rat cortical and retinal ganglion cell neurons; memantine also appears to be both safe and effective in a rat stroke model. These results suggest that memantine has considerable therapeutic potential for the myriad of clinical entities associated with NMDA receptor-mediated neurotoxicity.     

Modifying risk for extracorporeal circulation: trial of four antiinflammatory strategies

BACKGROUND: Despite recent rediscovery of beating heart cardiac surgical techniques, extracorporeal circulation remains appropriate for most heart operations. To minimize deleterious effects of cardiopulmonary bypass, antiinflammatory strategies have evolved. METHODS: Four state-of-the-art strategies were studied in a prospective, randomized, preoperatively risk stratified, 400-patient study comprising primary (n = 358), reoperative (n = 42), coronary (n = 307), valve (n = 27), ascending aortic (n = 9), and combined operations (n = 23). Groups were as follows: standard, roller pump, membrane oxygenator, methylprednisolone (n = 112); aprotinin, standard plus aprotinin (n = 109); leukocyte depletion, standard plus a leukocyte filtration strategy (n = 112); and heparin-bonded circuitry, centrifugal pumping with surface modification (n = 67). RESULTS: Analysis of variance, linear and logistic regression, and Pearson correlation were applied. Actual mortality (2.3%) was less than half the risk stratification predicted mortality (5.7%). The treatment strategies effectively attenuated markers of the inflammatory response to extracorporeal circulation. Compared with the other groups the heparin-bonded circuit had highly significantly decreased complement activation (p = 0.00001), leukocyte filtration blunted postpump leukocytosis (p = 0.043), and the aprotinin group had less fibrinolysis (p = 0.011). Primary end points, length of stay, and hospital charges, were positively correlated with operation type, age, pump time, body surface area, stroke, pulmonary sequelae, predicted risk for stroke, predicted risk for mortality, and risk strata/treatment group interaction (p = 0.0001). In low-risk patients, leukocyte filtration reduced length of stay by 1 day (p = 0.02) and mean charges by $2,000 to $6,000 (p = 0.05). For high-risk patients, aprotinin reduced mean length of stay up to 10 fewer days (p = 0.02) and mean charges by $6,000 to $48,000 (p = 0.0007). CONCLUSIONS: These pharmacologic and mechanical strategies significantly attenuated the inflammatory response to extracorporeal circulation. This translated variably into improved patient outcomes. The increased cost of treatment was offset for selected strategies through the added value of significantly reduced risk.     

Characterization of the excitable gap in human type I atrial flutter

OBJECTIVES: We sought to characterize the excitable gap of the reentrant circuit in atrial flutter. BACKGROUND: The electrophysiologic substrate of typical atrial flutter has not been well characterized. Specifically, it is not known whether the properties of the tricuspid valve isthmus differ from those of the remainder of the circuit. METHODS: Resetting was performed from two sites within the circuit: proximal (site A) and distal (site B) to the isthmus in 14 patients with type I atrial flutter. Resetting response patterns and the location where interval-dependent conduction slowing occurred were assessed. RESULTS: Some duration of a flat resetting response (mean +/- SD 40.1 +/- 20.9 ms, 16 +/- 8% of the cycle length) was observed in 13 of 14 patients; 1 patient had a purely increasing response. During the increasing portion of the resetting curve, interval-dependent conduction delay most commonly occurred in the isthmus. In most cases, the resetting response was similar at both sites. In three patients, the resetting response differed significantly between the two sites; this finding suggests that paced beats may transiently change conduction within the circuit or the circuit path, or both. CONCLUSIONS: Some duration of a flat resetting response was observed in most cases of type I atrial flutter, signifying a fully excitable gap in all portions of the circuit. The isthmus represents the portion of the circuit most vulnerable to interval-dependent conduction delay at short coupling intervals.     

Dopamine release in striatal slices of rats previously submitted to electroconvulsive shock

The effects of single and repeated electroconvulsive shock (ECS) on the release of dopamine from rat striatal slices were investigated using the fractional release technique. Experiments were performed 24 h after the single or the last of seven ECS sessions. Repeated, but not single, ECS was associated with reduced dopamine release in response to chemical stimulation. These results suggest that repeated ECS affects the regulation of striatal dopamine presynaptic receptors.