Multiple mechanisms of reflex bronchospasm in guinea pigs.

The mechanisms of histamine- and bradykinin-induced reflex bronchospasm were determined in anesthetized guinea pigs. With intravenous administration, both autacoids evoked dose-dependent increases in tracheal cholinergic tone. Vagotomy or atropine prevented these tracheal reflexes. When delivered as an aerosol, bradykinin readily increased tracheal cholinergic tone, whereas histamine aerosols were much less effective at inducing tracheal reflexes. Also, unlike histamine, bradykinin could evoke profound increases in cholinergic tone without directly or indirectly (e.g., prostanoid dependent) inducing measurable airway smooth muscle contraction resulting in bronchospasm. Neither autacoid required de novo synthesis of prostanoids or nitric oxide to induce reflex tracheal contractions. Combined cyclooxygenase inhibition and tachykinin-receptor antagonism did, however, abolish all effects of bradykinin in the airways, whereas responses to histamine were unaffected by these pretreatments. The data indicate that histamine and bradykinin initiate reflex bronchospasm by differential activation of vagal afferent nerve subtypes. We speculate that selective activation of either airway C fibers or airway rapid adapting receptors can initiate reflex bronchospasm.

The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, II: characteristics of patients enrolled and not enrolled. COMS Report No. 17.

OBJECTIVES: To describe characteristics of patients evaluated for the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of iodine 125 brachytherapy for choroidal melanoma by enrollment status, and to compare characteristics of patients enrolled with those of patients with tumors of eligible size who did not enroll in order to assess the extent to which findings from the clinical trial can be generalized to future patients. METHODS: For all patients diagnosed with choroidal melanoma and evaluated for the clinical trial at COMS centers from November 1986 through July 31, 1998, selected data were transmitted to the COMS Coordinating Center, Baltimore, Md, where they were integrated and analyzed. Data included ophthalmic and medical history, examination findings, and visual acuity measurements recorded prior to enrollment; standardized A- and B-scan echographic examination findings; and wide-angle fundus photographs and fluorescein angiograms. RESULTS: Of 8712 patients with choroidal melanoma, 5046 had tumors of eligible size; of these, 2882 (57%) were eligible for enrollment, and 1317 (46% of eligible patients, 26% of patients with tumors of eligible size) enrolled. Most differences between eligible and ineligible patients corresponded to eligibility and exclusion criteria. However, ineligible patients were older and had thicker tumors than eligible patients. Eligible patients who enrolled were slightly older and had larger tumors than those who did not enroll. Nearly half (48%) of enrolled patients had choroidal melanoma with the apex located temporal to the fovea, compared with 40% of eligible patients not enrolled and 29% of ineligible patients. CONCLUSIONS: This trial was designed to yield internally valid treatment comparisons through random assignment to treatment at time of enrollment. Information from this and other studies document that enrolled patients were similar to other patients with choroidal melanoma who were treated with 125I brachytherapy. These findings support the external validity of the trial and applicability of treatment findings to all patients who meet the criteria used to judge eligibility for the trial.

The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS Report No. 18.

OBJECTIVES: To report initial mortality findings from the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of iodine 125 brachytherapy vs enucleation for treatment of choroidal melanoma. METHODS: Patients were evaluated for eligibility at 43 participating clinical centers in the United States and Canada. Eligible consenting patients were assigned randomly at the time of enrollment to enucleation or 125I brachytherapy. Patients were examined at specified intervals after enrollment for data collection purposes. Findings presented herein are based on data received by September 30, 2000. Data for each patient were analyzed with the treatment group to which the patient was assigned randomly at the time of enrollment. RESULTS: During the 11(1/2)-year accrual period, 1317 patients enrolled; 660 were assigned randomly to enucleation and 657 to 125I brachytherapy. Only 2 patients in the enucleation arm were found to have been misdiagnosed when histopathology was reviewed centrally. All but 17 patients (1.3%) received the assigned treatment. Adherence to the brachytherapy protocol was excellent, with 91% of patients treated per protocol. Based on time since enrollment, 1072 patients (81%) had been followed for mortality for 5 years and 416 (32%) for 10 years. A total of 364 patients had died: 188 (28%) of 660 patients in the enucleation arm and 176 (27%) of 657 patients in the brachytherapy arm. The unadjusted estimated 5-year survival rates were 81% and 82%, respectively; there was no clinically or statistically significant difference in survival rates overall (P =.48, log-rank test). The adjusted estimated risk ratio for 125I brachytherapy vs enucleation was 0.99 (95% confidence interval [CI], 0.80-1.22). Five-year rates of death with histopathologically confirmed melanoma metastasis were 11% and 9% following enucleation and brachytherapy, respectively; after adjustment, the estimated risk ratio was 0.91 (95% CI, 0.66-1.24). CONCLUSIONS: Mortality rates following 125I brachytherapy did not differ from mortality rates following enucleation for up to 12 years after treatment of patients with choroidal melanoma who enrolled in this COMS trial. The power of the study was sufficient to indicate that neither treatment is likely to increase or decrease mortality rates by as much as 25% relative to the other.

Fear and feeding in the nucleus accumbens shell: rostrocaudal segregation of GABA-elicited defensive behavior versus eating behavior.

This study examined localization of positive versus negative motivational functions mediated by GABA circuits within the accumbens shell. Microinjections of a GABA(A) agonist (0, 25, 75, and 225 ng/0.5 microl muscimol) in rostral shell sites elicited appetitive increases in eating behavior. In contrast, microinjections in caudal shell sites elicited defensive burying or paw-treading behavior. Rats whose microinjections landed bilaterally outside of the accumbens shell did not display either behavior. Defensive treading elicited by caudal shell muscimol microinjection appeared to be a negative motivated response to threat (similar in parameters and orientation to normal defensive burying of a threatening electrified shock prod). The nucleus accumbens shell thus appears functionally heterogeneous in coding motivational valence. The demonstration that muscimol elicits positive eating behavior from rostral shell versus negative defensive behavior from caudal shell suggests in particular that GABAergic substrates of positive and negative types of motivated behavior in the nucleus accumbens shell are segregated along a rostrocaudal gradient.

Complications associated with limited macular translocation.

PURPOSE: To report the ocular complications associated with the limited macular translocation procedure. METHODS: Retrospective review of 153 consecutive eyes of 151 patients that had the limited macular translocation procedure for subfoveal choroidal neovascularization between April 1996 and February 1999. The major study variables investigated included the incidence of specific ocular complications and their impact on visual acuity at 3 months after the surgery. In addition, baseline patient characteristics and operative factors were evaluated to determine whether they were significant risk factors for the development of an ocular complication. The existence of a surgical procedure learning process was investigated. RESULTS: One hundred forty-one (92.15%) of 153 eyes achieved at least 3-month follow-up. At least one complication occurred in 53 of 153 eyes (34.6%) and in 51 of these 53 eyes (96. 22%) the complications occurred before 3 months of postoperative follow-up. The intraoperative and postoperative complications included retinal detachment (17.4%), retinal breaks (13.4%), macular holes (7.8%), macular fold (4.6%), and intraocular hemorrhage (vitreous, subretinal, or choroidal; 9.2%). Eyes that developed retinal detachment, subretinal hemorrhage, and macular fold had significantly more loss of visual acuity than eyes without each of these complications (P =.0001, P =.038, and P =.027, respectively). The presence of predominantly classic choroidal neovascularization, the occurrence of an intraoperative retinal break, any intraocular hemorrhage, or macular fold formation were significantly associated with retinal detachment (P =.021, P =.025, P =.013, and P =.014, respectively). The incidence of any complication, retinal detachment, and hemorrhage significantly decreased during the study period, suggesting a learning process (P =.03, P =.006, P =.027, respectively). CONCLUSIONS: A variety of ocular complications can occur during or after limited macular translocation, and some are associated with reduced postoperative visual acuity. Improved surgical techniques and experience may significantly reduce the incidence of these complications.

Limited inferior macular translocation for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: To review a series of patients with age-related macular degeneration undergoing limited macular translocation for the treatment of subfoveal choroidal neovascularization, to determine short-term visual acuity outcomes, to measure amounts of attainable retinal movement, and to identify prognostic factors. METHODS: A retrospective review was conducted on a consecutive series of patients undergoing inferior limited macular translocation with scleral imbrication for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration. The main outcome measures investigated were distance of macular translocation, visual acuity at 3 and 6 months after surgery, change in visual acuity from baseline, and the development of intraoperative and postoperative complications. Univariate and multivariate analyses of a number of potential prognostic factors were undertaken. RESULTS: Macular translocation was achieved in all 102 eyes (101 patients) included in this study. The range of movement varied from 200 to 2,800 microm with a median movement of 1, 200 microm. Nearly 33% of the study group achieved a visual acuity better than 20/100 at 3 months, and 49% achieved this vision at 6 months. At 3 and 6 months, 37% and 48% of the study group, respectively, experienced 2 or more lines of improvement on visual acuity testing, and by 6 months 16% experienced greater than 6 lines of visual improvement. Good baseline vision, achieving the desired amount of macular translocation, a greater amount of macular translocation, and recurrent choroidal neovascularization at baseline were associated with better visual acuities at 3 and 6 months. Poor preoperative vision and the development of complications were associated with worse vision at 3 and 6 months. CONCLUSIONS: Limited macular translocation is a technically feasible procedure that can lead to significant visual improvement and good visual acuity in some patients presenting with subfoveal choroidal neovascularization associated with age-related macular degeneration. A randomized prospective clinical trial of this surgical technique is warranted.

Evaluation of a xylene substitute in Ehrlich indole test.

Hemo-De (PMP Medical Industries, Inc., Irving, Tex.) was evaluated and found to be a suitable substitute for xylene in the Ehrlich modification of the indole test.

Nonmicrobial alternative to reagent quality control testing.

The traditional approach to quality control in microbiology involves the routine testing of both media and reagents with live microbial cultures. This is expensive, time consuming, and subject to the variables associated with the use of live organisms. A system of reagent quality control based on the pure chemical form of the metabolic end products important to the identification of the Enterobacteriaceae was evaluated. The metabolite reagent control system is simple, reliable, and extremely cost effective, and it eliminates the need for live microbial cultures and media for reagent quality control.