Xanthine oxidase inhibition after resuscitated hemorrhagic shock restores mesenteric blood flow without vasodilation.

To determine the contribution of xanthine oxidase-mediated reperfusion injury to the blood flow deficits seen in the intestinal microcirculation after resuscitated hemorrhagic shock, rats were prepared for intravital microscopic study then bled to 50% of baseline blood pressure for 60 min. Treatment animals received a 50 mg/kg bolus and a 25 mg/kg/h infusion of the xanthine oxidase inhibitor allopurinol after shock but before standard resuscitation with shed blood and an equal volume of Ringer's lactate. A similarly resuscitated group served as control. Blood flow and vessel diameters were measured in the neurovascularly intact terminal ileum using intravital microscopy and doppler velocimetry. Resuscitation restored cardiac output and blood pressure in both groups. Blood flow in first order arterioles 120 min postresuscitation was 41% of baseline in the standard resuscitation group and 77% of baseline in the allopurinol-treated group. A1 arteriolar diameter was not significantly different between the two groups, being 73 and 82% of baseline, respectively. These data suggest that xanthine oxidase-mediated ischemia-reperfusion injury contributes to blood flow deficits in the small intestinal microcirculation after resuscitated hemorrhagic shock and that the improvement in blood flow seen with allopurinol is not due to vasodilation within the microvasculature.

Pentoxifylline restores intestinal microvascular blood flow during resuscitated hemorrhagic shock.

We studied the intestinal microvascular blood flow responses to hemorrhage and resuscitation with pentoxifylline by in vivo video microscopy. Male Sprague-Dawley rats were hemorrhaged to 50% of baseline mean arterial pressure for 45 minutes and then blindly randomized to receive pentoxifylline (25 mg/kg bolus + 0.2 mg/kg/minute) or an equivalent volume of saline plus return of shed blood and an additional bled volume of Ringer's lactate solution. Hemorrhage caused intestinal microvascular blood flow to decrease to 10% to 15% of baseline values. In the control group, resuscitation restored cardiac output and mean arterial pressure to baseline values, but intestinal microvascular blood flow remained at 30% of baseline values. In contrast, addition of pentoxifylline to the resuscitation regimen resulted in an immediate hyperemic response with an increase in intestinal microvascular blood flow to significantly greater than baseline values followed by return to baseline. Arteriolar dilation was not responsible for the improvement in flow implicating improved flow dynamics between erythrocytes, granulocytes, and vascular endothelia within the microcirculation. We conclude that addition of pentoxifylline to resuscitation from hemorrhagic shock restores intestinal microvascular blood flow.

Antiestrogen-cytotoxic chemotherapy and bacillus Calmette-Guerin vaccination in stage II breast cancer: seventy-two-month follow-up.

A prospective, randomized clinical trial of adjuvant treatment of 312 stage II breast cancer patients with use of chemotherapy, antiestrogen therapy, and immunotherapy is reported after 72 months of follow-up. The stratification of patients was based on nodal involvement and estrogen receptor (ER) assay of the primary tumors. Findings at 72 months indicate that antiestrogen therapy (tamoxifen, Nolvadex) added to chemotherapy with cyclophosphamide (Cytoxan), methotrexate, and fluorouracil (5-Fluorouracil) (CMF) resulted in significant delayed recurrence in ER-positive postmenopausal patients, ER-positive patients with four or more positive nodes, and ER-positive patients with tumors greater than 3 cm in diameter. The addition of nonspecific immunotherapy with bacillus Calmette-Guerin had no effect on disease-free survival. ER and progesterone receptor measurements in patients with primary breast cancer provide valuable prognostic information on subsequent recurrence and overall survival and should be documented in future clinical trials.

Antiestrogen, cytotoxic chemotherapy, and bacillus Calmette-Guerin vaccination in stage II breast cancer: a preliminary report.

A prospective, randomized clinical trial of three treatment regimens: (1) Cytoxan, methotrexate, and 5-fluorouracil (CMF), (2) CMF plus the antiestrogen drug, tamoxifen (CMFT), and (3) CMFT plus bacillus Calmette-Guerin (BCG) vaccinations in women with stage 22 breast cancer is reported. All patients underwent mastectomy and estrogen receptor (ER) analysis was performed. The results of this study show that patients with ER- tumors have recurrences more rapidly and have a higher mortality rate than patients with ER+ tumors (P less than 0.0001). In ER+ patients CMFT treatment is more effective in delaying recurrence than CMF alone at 33 months (P = 0.0176). This effect appears to be occurring in both premenopausal and postmenopausal women. In ER- patients the recurrence rate is high, and there is no significant difference among the three treatment groups. In premenopausal patients treated with CMF alone, however, ER- patients recur more rapidly than ER+ patients (P = 0.0313) and suggests that the effect of CMF may be related to the suppression of ovarian function. These findings have demonstrated a significant role for the use of antiestrogen therapy in patients with state II, ER+ breast cancer.

Reappraisal of pancreatic and duodenal injury management based on injury severity.

We evaluated the effectiveness of treatment protocols for pancreatic and duodenal injuries according to the severity of injury. Of 81 patients, 65 survived initial injury. Pancreatic injuries without ductal involvement occurred in 21 patients and were treated by drainage. No late deaths occurred. Pancreatic injuries with ductal disruption occurred in 18 patients and were treated by pancreatic resection. Abscesses developed in seven (39%) of the patients, but no late deaths occurred. Nineteen patients had duodenal injuries without pancreatic injury, and no duodenal complications occurred. Simple closure sufficed for injuries affecting up to 40% of the duodenal circumference. Wounds affecting up to 40% of the duodenal circumference can be treated by suture closure alone. Adjunctive duodenal tube decompression should be reserved for wounds affecting greater than 40% of the duodenal circumference, closure under tension, and associated injuries to the head of the pancreas. Pyloric exclusion was rarely necessary in our patients.

Laser synechialysis to prevent membrane recurrence on silicone intraocular lenses.

PURPOSE: To determine whether laser posterior synechialysis will prevent recurrence of pigmented membranes that can form on the anterior surface of silicone intraocular lenses. METHODS: Three patients (four eyes) had posterior synechiae and silicone intraocular lens surface membranes that required long-term corticosteroid treatment. Posterior synechiae were lysed by an Nd:YAG laser (1 to 2 mJ per burst; 148 to 485 applications; total energy, 296 to 896 mJ). RESULTS: All four eyes remained free of recurrence from 12 to 14 months. CONCLUSIONS: Silicone intraocular lens surface membranes emanated from posterior synechiae. The Nd:YAG laser synechialysis prevented recurrence and allowed discontinuation of corticosteroids.

Delayed hyphema and intravitreal blood following intrableb autologous blood injection after trabeculectomy.

PURPOSE: To report delayed hyphema and intravitreal blood as complications following intrableb autologous blood injection after trabeculectomy. METHODS: Case report. A 44-year-old woman with hypotony and maculopathy after trabeculectomy with mitomycin C received an intrableb autologous blood injection. RESULTS: Three days after the blood injection, a hyphema formed and subsequently dispersed into the vitreous. CONCLUSIONS: Although immediate hyphema from autologous blood injection is common, hyphema may be delayed and associated with intravitreal blood.

Mitomycin trabeculectomy: the microsurgical sponge difference.

OBJECTIVE: A reproducible method for mitomycin application during glaucoma surgery is necessary to compare clinical results among investigators. To evaluate the potential reliability in drug delivery characteristics, mitomycin absorption and release from microsurgical sponges was studied. METHODS: Four brands of commercially available sponges were compared using a 0.5 mg/ml concentration of mitomycin. First, the maximum volume each sponge could absorb was measured. Second, 0.2 ml was applied to each sponge and then the expansion width was measured. Finally, 0.2 ml was applied to each sponge, the sponge was placed on filter paper, and then the amount (by weight) each sponge released during a 31/2-min period was measured. RESULTS: The volume absorbed was similar for each brand; the means ranged from 0.44 to 0.52 ml. The expansion width was variable between the brands; the means ranged from 4.0 to 10.4 mm. The amount released to filter paper was also variable between the brands; the means ranged from 19 to 54 mg. CONCLUSIONS: The difference in delivery characteristics suggests that the microsurgical sponge may be an important variable in mitomycin application. In absence of a standardized method, more detailed descriptions about specific mitomycin techniques are needed.

Brain injury causes loss of cardiovascular response to hemorrhagic shock.

The combined cardiovascular effects of hemorrhagic shock and mechanical brain injury were modeled in five groups of pigs. Standard and hypertonic saline resuscitation of hypotension were evaluated. Changes in mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), intracranial pressure (ICP), and brain water were measured. Brain injury (BI) was produced with a fluid percussion device that generated an extradural pressure of 3.5 x 10(5) N/m2 for 400 msec. Shock was caused by bleeding to a MAP of 60 mm Hg for 60 minutes and then resuscitated with shed blood only or shed blood plus 0.9% or 1.8% saline. Brain-injured only and shocked-only pigs served as controls. We found that brain injury alone caused refractory hypotension. Less shed blood was required to produce shock in brain injured animals (p < .05). Shock accompanied by brain injury was not reversed with crystalloid solutions. Volumes of saline required to restore blood pressure were large (> 6 L in 3 hours). 1.8% saline produced less rise in ICP than 0.9% saline but was less effective in restoring blood pressure. Brain edema was not decreased with 1.8% saline. Brain injury altered vascular compensation to hemorrhage and made accepted resuscitative measures ineffective.

The use of contact lenses by USAF aviators.

Contact lenses are an alternative method to spectacles for correcting refractive errors, but the U.S. Air Force prohibits the wearing of contact lenses by all aircrew members unless medically or optically indicated (AFR 167-3). USAFSAM has a clinical contact lens study consisting of 55 individuals wearing contact lenses for eye defects such as keratoconus, aphakia, anisometropia, and other special indications. Of these 55 individuals, 33 had medical conditions affecting their vision and were unconditionally grounded. Of these individuals, 31 (18 of 19 pilots, 8 of 9 navigators, 5 of 5 other categories) were visually rehabilitated and returned to full flight status by the use of contact lenses. Hard lenses were used in 70% of the cases and soft lenses in 30%. The large number of USAF aviators required to wear spectacles and new head-borne equipment has created compatibility problems with the standard USAF aviators' spectacle. For this spectacle compatibility problem, contact lenses appear as a viable alternative. However, for wide-spread use, concerns remain about the potential aviation hazards, such as +Gz effects, bubble formation, and corneal hypoxia.

Retinal vein occlusions: case reviews of USAF aviators.

Retinal vein occlusions are primarily a disease of the elderly, frequently with permanent visual abnormalities. However, both branch and central retinal vein occlusions occur rarely in young individuals. Reported here are a series of retinal vein occlusions in USAF aviators. Seven cases were identified from records of the USAF Armstrong Laboratory Aeromedical Consultation Service from 1976-91. Four cases of central retinal vein occlusions and three cases of branch occlusions are summarized. Initial visual acuity ranged from 20/15 to 20/400. All seven aviators recovered 20/15 vision and returned to flying status. Hyperlipidemia was found in four of the seven aviators, and hypertension was diagnosed in two aviators. Included is a discussion of current concepts in the natural history, associated systemic conditions, treatment options, and aeromedical implications of retinal vein occlusions.

Effect of positive acceleration (+Gz) on soft contact lens wear.

The effects of positive acceleration on soft contact lens wear were tested on a human centrifuge to +8 Gz. There were 11 subjects who participated in this study; 5 were myopic subjects fit with low-, medium-, and high-water-content spherical soft lenses; 3 were astigmatic subjects fit with various designs of toric soft lenses and 3 were emmetropic control subjects. As an additional control, the contact lens subjects were tested with spectacles for comparison. Video photography was used to monitor lens position during the centrifuge rides and visual acuity was checked at +1, +2, +4, +6, and +8 Gz with a reduced Snellen eye chart. Each lens type and control run was evaluated in straight-ahead, lateral, and vertical gaze. No visually significant decentration was noted for any of the lens types tested up to the maximum level of +8 Gz. Visual acuity was reduced at the higher +Gz levels for contact lenses, and spectacle trials, and with the emmetropic controls--all to similar levels. Contact lens wear did not produce any corneal insult due to the +Gz exposure.

Soft contact lens wear at altitude: effects of hypoxia.

In the U.S. Air Force, aircraft can be divided into two categories--those with cabin pressures equivalent to high altitudes and aircraft with cabin pressures equivalent to lower altitudes, with longer duration exposures. The purpose of this study was to determine the effects of soft contact lens wear under atmospheric pressures simulating these two types of aircraft environments. Ten subjects were tested to 7620 m (25,000 ft) in hypobaric chamber flights of 75 min and eight subjects were tested in hypobaric chamber flights at 3048 m (10,000 ft) for 4 h. Four subjects were also tested in dry air to further simulate cabin conditions. Vision and physiologic response were monitored by measurements of visual acuity, contrast sensitivity, and slit-lamp biomicroscopy examinations. The results of this study indicate that the physiologic responses of the cornea to soft contact lens wear at altitude are subject to higher levels of manifested stresses, but these occurred without measurable degradation in vision and did not preclude normal wear of soft contact lenses.

Contact lens wear at altitude: subcontact lens bubble formation.

A concern in the past regarding contact lens wear in aviation has been the fear of subcontact lens bubble formation. Previous reports have documented the occurrence of bubbles with hard (PMMA) lenses. Reported here are the results of contact lens bubble studies with soft hydrophilic and rigid gas-permeable lenses. Testing was accomplished in hypobaric chambers and onboard USAF transport aircraft. Hypobaric chamber flights were of three types: high-altitude flights up to 7,620 m (25,000 ft); explosive rapid decompressions from 2,438.4 m (8,000 ft) to 7,620 m (25,000 ft); and 4-h flights at 3,048 m (10,000 ft). Flights aboard transport aircraft typically had cabin pressures equivalent to 1,524-2,438.4 m (5,000-8,000 ft), and ranged in duration from 3 to 10 h. For subjects wearing rigid gas-permeable lenses, central bubbles were detected in 2 of 10 eyes and occurred at altitudes greater than 6,096 m (20,000 ft). With soft contact lenses, bubble formation was detected in approximately 24% (22 of 92 eyes) of the eyes tested, sometimes occurring at altitudes as low as 1,828.8 m (6,000 ft). Soft lens bubbles were always located at the limbus and were without sequela to vision or corneal epithelial integrity. Bubbles under the rigid lenses were primarily central, with potential adverse effects on vision and the corneal epithelium.

Hypotonic exposures.

Even without a contact lens, the cornea can suffer adverse physiological changes from hypotonic exposure, as well as the associated subjective phenomena (e.g., halo and rainbows). The contact lens adds a dimension to this problem that should be viewed against a background of normal (non-wearing) susceptibilities.