Evolution of nectar spur length in a clade of Linaria reflects changes in cell division rather than in cell expansion.

Background and Aims: Nectar spurs (tubular outgrowths of a floral organ which contain, or give the appearance of containing, nectar) are hypothesized to be a 'key innovation' which can lead to rapid speciation within a lineage, because they are involved in pollinator specificity. Despite the ecological importance of nectar spurs, relatively little is known about their development. We used a comparative approach to investigate variation in nectar spur length in a clade of eight Iberian toadflaxes. Methods: Spur growth was measured at the macroscopic level over time in all eight species, and growth rate and growth duration compared. Evolution of growth rate was reconstructed across the phylogeny. Within the clade we then focused on Linaria becerrae and Linaria clementei, a pair of sister species which have extremely long and short spurs, respectively. Characterization at a micromorphological level was performed across a range of key developmental stages to determine whether the difference in spur length is due to differential cell expansion or cell division. Key Results: We detected a significant difference in the evolved growth rates, while developmental timing of both the initiation and the end of spur growth remained similar. Cell number is three times higher in the long spurred L. becerrae compared with L. clementei, whereas cell length is only 1.3 times greater. In addition, overall anisotropy of mature cells is not significantly different between the two species. Conclusions: We found that changes in cell number and therefore in cell division largely explain evolution of spur length. This contrasts with previous studies in Aquilegia which have found that variation in nectar spur length is due to directed cell expansion (anisotropy) over variable time frames. Our study adds to knowledge about nectar spur development in a comparative context and indicates that different systems may have evolved nectar spurs using disparate mechanisms.

Standardized programming to reduce the burden of inappropriate therapies in implantable cardioverter defibrillators - Single centre follow up results.

BACKGROUND: Current algorithms and device morphology templates have been proposed in current Implantable Cardioverter-Defibrillators (ICDs) to minimize inappropriate therapies (ITS), but this has not been completely successful. AIM: Assess the impact of a deliberate strategy of using an atrial lead implant with standardized parameters; based on all current ICD discriminators and technologies, on the burden of ITS. METHOD: A retrospective single-centre analysis of 250 patients with either dual chamber (DR) ICDs or biventricular ICDs (CRTDs) over a (41.9 ± 27.3) month period was performed. The incidence of ITS on all ICD and CRTD patients was chronicled after the implementation of standardized programming. RESULTS: 39 events of anti-tachycardial pacing (ATP) and/or shocks were identified in 20 patients (8% incidence rate among patients). The total number of individual therapies was 120, of which 34% were inappropriate ATP, and 36% were inappropriate shocks. 11 patients of the 250 patients received ITS (4.4%). Of the 20 patients, four had ICDs for primary prevention and 16 for a secondary prevention. All the episodes in the primary indication group were inappropriate, while seven patients (43%) of the secondary indication group experienced inappropriate therapies. CONCLUSIONS: The burden of ITS in the population of patients receiving ICDs was 4.4% in the presence of atrial leads. The proposed rationalized programming criteria seems an effective strategy to minimize the burden of inappropriate therapies and will require further validation.

Applications of cardiac computed tomography in electrophysiology intervention.

Cardiac electrophysiology is an evolving specialty that has seen rapid advances in recent years. Concurrently, there has been much progress in the field of cardiac imaging. Electrophysiologists are increasingly requesting cross-sectional imaging in advance of many procedures. Pulmonary vein isolation and left atrial appendage (LAA) occlusion are now an established treatment options for atrial fibrillation. In patients undergoing pulmonary vein isolation, applications of computed tomography (CT) include evaluating the left atrial and pulmonary venous anatomy, excluding LAA thrombus and assessing for pulmonary vein stenosis. In those undergoing LAA occlusion, CT may be of value in assessing the size, position, and morphology of the LAA as well as for determining correct positioning of the device and evaluating for peri-device leak. Implantable cardiac devices are now commonly used in the management of cardiac failure and cardiac arrhythmias. Applications of CT prior to device implantation include detecting myocardial scar, evaluating for mechanical dyssynchrony as well as visualising the coronary venous anatomy.

Use of frequency analysis on the ECG for the prognosis of low energy cardioversion treatment of atrial fibrillation.

Electric cardioversion is the most effective therapy for restoring sinus rhythm in patient with atrial fibrillation (AF), however, there is not a guiding criteria for advising on when and in whom it will be successful. The objective of this study was to employ frequency analysis on the surface electrocardiogram (ECG) to predict the outcome of low energy internal cardioversion in patients with AF. Thirty nine patients with AF, for elective DC cardioversion were included in this study. One catheter was positioned in the right atrial appendage and another in the coronary sinus. A voltage step-up protocol (50-300 V) was used for patient cardioversion. Prior to shock delivery, residual atrial activity signal (RAAS) was derived from 60 seconds of surface ECG from defibrillator pads, by bandpass filtering and ventricular activity (QRST) cancellation. Dominant atrial fibrillatory frequency (DAFF) was estimated from the RAAS power spectrum as the dominant frequency within the 3-12 Hz band. DAFF was calculated from whole 60 seconds segment (DAFF_L) and from the finals 10 seconds segment (DAFF_S) of the RAAS. Lower DAFF_L and DAFF_S were found in successfully cardioverted patients than in those nonsuccessful ones, with energy < or =3 and < or =6 joules. Therapy result (employing 3J or less) was predicted in 35/39 (89.7%) patients with DAFF_L=5.40Hz, and DAFF_L was > or =5.75Hz in a 100% of noncardioverted patients. In conclusion, frequency analysis of the RAAS could be useful for predicting success of low energy internal cardioversion of patients with atrial fibrillation.

ST elevation on the exercise ECG in patients presenting with chest pain and no prior history of myocardial infarction.

OBJECTIVE: To assess the aetiology, and prognosis of ST-segment elevation (STE) on the exercise electrocardiogram in patients with chest pain without a prior history of myocardial infarction (MI). METHODS: Between January 1998 and December 2005, 14 941 exercise stress tests were performed to assess chest pain in patients without a prior history of MI. Those who developed STE were identified. RESULTS: STE occurred in 0.78% (116/14 941). Coronary angiography was performed in 108 patients. All patients had at least one severe coronary artery stenosis (>70%). The site of STE on exercise ECG was shown to be 95.4% predictive of a severe stenosis in the coronary artery supplying that area. Lateral STE was rare (1/116). Ninety-eight patients underwent revascularisation; 67 patients had percutaneous coronary intervention (PCI) and 31 underwent coronary artery bypass grafting (CABG). Follow-up included recording of death, MI, cerebrovascular event, heart failure and target vessel revascularisation. The projected 7-year event-free survival probability was 62.1% for those undergoing CABG, 77.1% for those who had PCI and 68.6% for those not undergoing revascularisation (no difference between these three groups, log rank p = 0.802). CONCLUSIONS: STE on the exercise ECG is rare but specific for ischaemic heart disease and is predictive of a severe stenosis in the corresponding coronary artery. Prognosis is favourable following revascularisation.

Investigation of a multimarker approach to the initial assessment of patients with acute chest pain.

Early identification of acute coronary syndrome (ACS) is important to guide therapy at a time when it is most likely to be of value. In addition, predicting future risk helps identify those most likely to benefit from ongoing therapy. Cardiac troponin T (cTnT) is useful for both purposes although cannot reliably rule out ACS until 12 hours after pain onset and does not fully define future risk. In this review article we summarize our previously published research, which assessed the value of myocyte injury, vascular inflammation, hemostatic, and neurohormonal markers in the early diagnosis of ACS and risk stratification of patients with ACS. In addition to cTnT, we measured heart fatty acid binding protein (H-FABP), glycogen phosphorylase-BB, high-sensitivity C-reactive protein, myeloperoxidase, matrix metalloproteinase 9, pregnancy-associated plasma protein-A, D-dimer, soluble CD40 ligand, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Of the 664 patients enrolled, 415 met inclusion criteria for the early diagnosis of acute myocardial infarction (MI) analysis; 555 were included in the risk stratification analysis and were followed for 1 year from admission. In patients presenting <4 hours from pain onset, initial H-FABP had higher sensitivity for acute MI than cTnT (73% vs. 55%; P=0.043) but was of no benefit beyond 4 hours when compared to cTnT. On multivariate analysis, H-FABP, NT-proBNP, and peak cTnT were independent predictors of 1-year death/MI. Our research demonstrated that, in patients presenting within 4 hours from pain onset, H-FABP may improve detection of ACS. Measuring H-FABP and proBNP may help improve long-term risk stratification.

The Northern Ireland Public Access Defibrillation (NIPAD) study: effectiveness in urban and rural populations.

OBJECTIVE: To assess the impact of mobile automated external defibrillators (AEDs) on out-of-hospital cardiac arrests (OHCAs) in urban and rural populations. DESIGN: Prospective before and after intervention, population study. SETTING: Urban and rural areas of 160,000 each. Patients, interventions and MAIN OUTCOME MEASURES: In 2004-6 the demographics of OHCAs were assessed. In 2005-6 AEDs were deployed (29 urban, 53 rural): 335 urban first responders (FRs) and 493 rural FRs were trained in AED use and dispatched to OHCAs. Call-to-response interval (CRI), resuscitation and survival-to-discharge rates for OHCA were compared. RESULTS: In 2004 there were 163 urban OHCAs and the emergency medical services (EMS) attended 158 (ventricular fibrillation (VF) 27/158 (17.1%)). In 2005-6 there were 226 OHCAs, EMS attended 216 (VF 30/216 (13.9%)). In 2005-6 FRs were paged to 128 OHCAs (56.6%), FRs attended 88/128 (68.8%): 18/128 (14.1%) reached before the EMS. The best combined FR/EMS mean (SD) CRI in 2005-6 (5 min 56 s (4)) was better than the EMS alone in 2004 (7 min (3); p = 0.002). Survival rate was 5.1% in 2004, 1.4% in 2005-6 (p = NS). In 2004 there were 131 rural OHCAs, EMS attended 121 (VF 19/121 (15.7%)). In 2005-6 there were 122 OHCAs, EMS attended 114 (VF 19/114 (16.7%)). In 2005-6 FRs were paged to 49 OHCAs, FRs attended 42/49 (85.7%): 23/49 (46.9%) reached before the EMS. The best combined FR/EMS mean (SD) CRI in 2005-6 (9 min 22 s (6)) was better than the EMS alone in 2004 (11 min 2 s (6); p = 0.018). Survival rate was 2.5% in 2004, 3.5% in 2005-6 (p = NS). CONCLUSIONS: Despite improvement in CRI there was no impact on survival (witnessed arrest 32.8%, VF 15.6%). TRIAL REGISTRATION NUMBER: ISRCTN07286796.

Nonlinear analysis of the ECG during atrial fibrillation in patients for low energy internal cardioversion.

The goal of this study was to investigate the usefulness of nonlinear analysis in determining the success of low energy internal cardioversion (IC) in patients with atrial fibrillation (AF). Nonlinear analysis has previously been used for characterizing AF patterns, and spontaneous termination in its paroxysmal form. However, the relationship between the probability to restore sinus rhythm by IC and quantitative nonlinear analysis based electrocardiographic (ECG) markers has not been explored before. Thirty nine patients with AF, for elective DC cardioversion at the Royal Victoria Hospital in Belfast, were included in this study. One catheter was positioned in the right atrial appendage and another in the coronary sinus, to deliver a biphasic shock waveform. A voltage step-up protocol (50-300 V) was used for patient cardioversion. Residual atrial fibrillatory signal (RAFS) was derived from 60 seconds of surface ECG from defibrillator pads, prior to shock delivery, by bandpass filtering and ventricular activity (QRST) cancellation. QRST complexes were cancelled using a recursive least squared (RLS) adaptive filter. The maximal Lyapunov exponent (lambda), correlation dimension (course grained estimation, CDcg) and approximate entropy (ApEn) were extracted from the RAFS. These variables were calculated from 10 s of the RAFS before shock delivery. 26 patients were successfully cardioverted, employing a maximum energy of 11.84 joules. A lower lambda (0.037+/-0.006 vs. 0.044+/-0.008, P=0.01) and CDcg (5.552+/-2.075 vs. 6.592+/-1.130, P=0.049) were found in successfully cardioverted patients than in those non successful ones, with an energy

Biphasic energy selection for transthoracic cardioversion of atrial fibrillation. The BEST AF Trial.

AIMS: To compare the efficacy and safety of an escalating energy protocol with a non-escalating energy protocol using an impedance compensated biphasic defibrillator for direct current cardioversion of atrial fibrillation (AF). METHODS AND RESULTS: This prospective multicentre randomised trial enrolled 380 patients (248 male, mean (SD) age 67 (10) years) with AF. Patients were randomised to either an escalating energy protocol (protocol A: 100 J, 150 J, 200 J, 200 J), or a non-escalating energy protocol (protocol B: 200 J, 200 J, 200 J). Cardioversion was performed using an impedance compensated biphasic waveform. First-shock success was significantly higher for those randomised to 200 J than 100 J (71% vs 48%; p<0.01) and for patients with a body mass index (BMI) >25 kg/m(2) (75% vs 44%; p = 0.01). In patients with a normal BMI there was no significant difference in first-shock success. There was also no significant difference between subsequent shocks or overall success. The use of a non-escalating protocol (protocol B) resulted in fewer shocks but with a higher cumulative energy. There was no difference in duration of procedure, amount of sedation administered or post-shock erythema between the groups. CONCLUSION: First-shock success was significantly higher, particularly in patients with a BMI >25 kg/m(2), when a non-escalating initial 200 J energy was selected. The overall success, duration of procedure and amount of sedation administered, however, did not differ significantly between the two protocols.

The effect of internal DC shocks on the atrial fibrillation frequency.

The objective of this study, was to investigate the effect of internal DC shocks on the atrial fibrillation frequency (AFF). AFF has previously been shown to predict the success and energy requirements in patients undergoing internal cardioversion (IC) of atrial fibrillation (AF). However the possibility that unsuccessful shocks during IC may influence the AFF has not been before studied. Thirty eight patients with AF, suggested for DC cardioversion at the Royal Victoria Hospital in Belfast, were included in our study. Two catheters were positioned in the right atrial appendage (RAA) and the coronary sinus (CS), to deliver a biphasic shock waveform, synchronized with the R wave of the electrocardiogram (ECG) signal. A voltage step-up protocol (50-300 V) was used for patient cardioversion. The ECG was analyzed for a mean of 52,8+/-10.1 seconds (corresponding to segments before and after nonsuccessful shocks). Atrial fibrillatory activity was extracted by means of bandpass filtering and ventricular activity (QRST) cancellation. QRST complexes were cancelled using a recursive least squared (RLS) adaptive filter. FFT was applied to the residual atrial fibrillatory signal. AFF was estimated from the dominant frequency within the 3-12 Hz band of the power spectrum. R-R intervals during the segments were also analyzed. A total of 26 patients were successfully cardioverted, employing 167 shocks (141 nonsuccessful). AFF, computed with 10 s of signal, showed significant reduction (mean 0.3052 +/- 1.1055 Hz, P=0.028) comparing segments immediately before and after shocks, and AFF significantly increases (mean 0.2582 +/- 0.609 Hz, P=0.007) between segments immediately after shocks and those 35 s after. AFF showed distinct behavior according to the energy level of the shocks. In conclusion, intracardiac electric shocks could cause transitory changes in the AFF of patients with atrial fibrillation.

Demographic and temporal trends in out of hospital sudden cardiac death in Belfast.

OBJECTIVE: To determine the epidemiology of out of hospital sudden cardiac death (OHSCD) in Belfast from 1 August 2003 to 31 July 2004. DESIGN: Prospective examination of out of hospital cardiac arrests by using the Utstein style and necropsy reports. World Health Organization criteria were applied to determine the number of sudden cardiac deaths. RESULTS: Of 300 OHSCDs, 197 (66%) in men, mean age (SD) 68 (14) years, 234 (78%) occurred at home. The emergency medical services (EMS) attended 279 (93%). Rhythm on EMS arrival was ventricular fibrillation (VF) in 75 (27%). The call to response interval (CRI) was mean (SD) 8 (3) minutes. Among patients attended by the EMS, 9.7% were resuscitated and 7.2% survived to leave hospital alive. The CRI for survivors was mean (SD) 5 (2) minutes and for non-survivors, 8 (3) minutes (p < 0.001). Ninety one (30%) OHSCDs were witnessed; of these 91 patients 48 (53%) had VF on EMS arrival. The survival rate for witnessed VF arrests was 20 of 48 (41.7%): all 20 survivors had VF as the presenting rhythm and CRI < or = 7 minutes. The European age standardised incidence for OHSCD was 122/100,000 (95% confidence interval 111 to 133) for men and 41/100,000 (95% confidence interval 36 to 46) for women. CONCLUSION: Despite a 37% reduction in heart attack mortality in Ireland over the past 20 years, the incidence of OHSCD in Belfast has not fallen. In this study, 78% of OHSCDs occurred at home.

tau binds and organizes Escherichia coli replication proteins through distinct domains: domain III, shared by gamma and tau, oligomerizes DnaX.

The tau and gamma proteins of the DNA polymerase III holoenzyme DnaX complex are products of the dnaX gene with gamma being a truncated version of tau arising from ribosomal frameshifting. tau is comprised of five structural domains, the first three of which are shared by gamma (Gao, D., and McHenry, C. (2001) J. Biol. Chem. 276, 4433-4453). In the absence of the other holoenzyme subunits, DnaX exists as a tetramer. Association of delta, delta', chi, and psi with domain III of DnaX(4) results in a DnaX complex with a stoichiometry of DnaX(3)deltadelta'chipsi. To identify which domain facilitates DnaX self-association, we examined the properties of purified biotin-tagged DnaX fusion proteins containing domains I-II or III-V. Unlike domain I-II, treatment of domain III-V, gamma, and tau with the chemical cross-linking reagent BS3 resulted in the appearance of high molecular weight intramolecular cross-linked protein. Gel filtration of domains I-II and III-V demonstrated that domain I-II was monomeric, and domain III-V was an oligomer. Biotin-tagged domain III-V, and not domain I-II, was able to form a mixed DnaX complex by recruiting tau, delta, delta', chi, and psi onto streptavidin-agarose beads. Thus, domain III not only contains the delta, delta', chi, and psi binding interface, but also the region that enables DnaX to oligomerize.

The DNA polymerase III holoenzyme: an asymmetric dimeric replicative complex with leading and lagging strand polymerases.

The DNA Polymerase III holoenzyme forms initiation complexes on primed DNA in an ATP-dependent reaction. We demonstrate that the nonhydrolyzable ATP analog, ATP gamma S, supports the formation of an isolable leading strand complex that loads and replicates the lagging strand only in the presence of ATP, beta, and the single-stranded DNA binding protein. The single endogenous DnaX complex within DNA polymerase III holoenzyme assembles beta onto both the leading and lagging strand polymerases by an ordered mechanism. The dimeric replication complex disassembles in the opposite order from which it assembled. Upon ATP gamma S-induced dissociation, the leading strand polymerase is refractory to disassembly allowing cycling to occur exclusively on the lagging strand. These results establish holoenzyme as an intrinsic asymmetric dimer with distinguishable leading and lagging strand polymerases.

Regioselective palladium-catalyzed arylation of 2-furaldehyde.

An efficient regioselective method for the direct arylation of 2-furaldehyde to provide a range of pi-diverse 5-aryl-2-formylfuran derivatives is described. The method employs functionalized aryl halides and a catalytic amount of palladium(II) chloride under relatively mild conditions.

A novel assembly mechanism for the DNA polymerase III holoenzyme DnaX complex: association of deltadelta' with DnaX(4) forms DnaX(3)deltadelta'.

We have constructed a plasmid-borne artificial operon that expresses the six subunits of the DnaX complex of Escherichia coli DNA polymerase III holoenzyme: tau, gamma, delta, delta', chi and psi. Induction of this operon followed by assembly in vivo produced two taugamma mixed DnaX complexes with stoichiometries of tau(1)gamma(2)deltadelta'chipsi and tau(2)gamma(1)deltadelta'chipsi rather than the expected gamma(2)tau(2)deltadelta'chipsi. We observed the same heterogeneity when taugamma mixed DnaX complexes were reconstituted in vitro. Re-examination of homomeric DnaX tau and gamma complexes assembled either in vitro or in vivo also revealed a stoichiometry of DnaX(3)deltadelta'chipsi. Equilibrium sedimentation analysis showed that free DnaX is a tetramer in equilibrium with a free monomer. An assembly mechanism, in which the association of heterologous subunits with a homomeric complex alters the stoichiometry of the homomeric assembly, is without precedent. The significance of our findings to the architecture of the holoenzyme and the clamp-assembly apparatus of all other organisms is discussed.

Differentiation in plant epidermal cells.

The plant epidermis is a multifunctional tissue playing important roles in water relations, defence and pollinator attraction. This range of function is performed by a number of different types of specialized cells, which differentiate from the early undifferentiated epidermis in adaptively significant patterns and frequencies. These various cells show different degrees of morphological specialization, but there is evidence to suggest that even the less specialized cell types may require certain signals to ensure their correct differentiation and patterning. Epidermal cells may potentially adopt certain fates through a cell lineage based mechanism or a cell interaction mechanism. Work on stomatal development has focused on the cell lineage mechanism and work on trichome differentiation has focused on the cell interaction model. Recent work on the Arabidopsis trichome suggests that interactions between neighbouring cells reinforce initial differences, possibly in levels of gene expression or cell cycle stage, to commit cells to different developmental programmes. In this review these mechanisms are explored in a number of specialized cell types and the further interactions between different developmental programmes are analysed. It is in these interactions between differentiating cells adopting different cell fates that the key to the patterning of a multifunctional tissue must lie.

The DnaX-binding subunits delta' and psi are bound to gamma and not tau in the DNA polymerase III holoenzyme.

The DnaX complex subassembly of the DNA polymerase III holoenzyme is comprised of the DnaX proteins tau and gamma and the auxiliary subunits delta, delta', chi, and psi, which together load the beta processivity factor onto primed DNA in an ATP-dependent reaction. delta' and psi bind directly to DnaX whereas delta and chi bind to delta' and psi, respectively (Onrust, R., Finkelstein, J., Naktinis, V., Turner, J., Fang, L., and O'Donnell, M. (1995) J. Biol. Chem. 270, 13348-13357). Until now, it has been unclear which DnaX protein, tau or gamma, in holoenzyme binds the auxiliary subunits delta, delta', chi,and psi. Treatment of purified holoenzyme with the homobifunctional cross-linker bis(sulfosuccinimidyl)suberate produces covalently cross-linked gamma-delta' and gamma-psi complexes identified by Western blot analysis. Immunodetection of cross-linked species with anti-delta' and anti-psi antibodies revealed that no tau-delta' or tau-psi cross-links had formed, suggesting that the delta' and psi subunits reside only on gamma within holoenzyme.

Efficacy of apraclonidine 1% versus pilocarpine 4% for prophylaxis of intraocular pressure spike after argon laser trabeculoplasty.

OBJECTIVE: The authors compared the efficacy of apraclonidine 1% versus pilocarpine 4% prophylaxis of post-argon laser trabeculoplasty (ALT) intraocular pressure (IOP) spike. DESIGN: Prospective randomized clinical trial. PARTICIPANTS: Two hundred twenty-eight eyes of 228 patients with primary open-angle glaucoma undergoing ALT were studied. INTERVENTION: Patients were given 1 drop of either apraclonidine 1% (n = 114) or pilocarpine 4% (n = 114) 15 minutes before ALT. MAIN OUTCOME MEASURES: Peri-ALT IOPs and incidences of post-ALT IOP spikes at 5 minutes, 1 hour, and 24 hours were compared between the two groups. RESULTS: The two groups were similar in age, race, and medical dependency. Post-ALT mean IOPs at 5 minutes, 1 hour, and 24 hours were significantly lower than pre-ALT mean IOPs in both apraclonidine (P < 0.001) and pilocarpine (P < 0.001) groups. Incidences of IOP spikes greater than 1, 3, and 5 mmHg at 1 hour post-ALT were 21.1%, 14.9%, and 8.8% for the apraclonidine group and 12.3%, 5.3%, and 4.4% for the pilocarpine group (P = 0.076, 0.015, and 0.18 chi-square test). In the apraclonidine prophylaxis group, patients on long-term apraclonidine showed significantly higher incidence of post-ALT IOP spike than the patients without such long-term apraclonidine use (35.7%, 15 of 42 eyes, vs. 12.5%, 9 of 72 eyes; P = 0.003). In addition, peri-ALT pilocarpine prophylaxis tended to be less effective in patients undergoing long-term pilocarpine therapy but without statistical significance (17.4%, 8 of 46 eyes, vs. 9.4%, 6 of 64 eyes; P = 0.17). CONCLUSION: Peri-ALT pilocarpine 4% was at least as effective as, if not more effective than, apraclonidine 1% in post-ALT IOP spike prophylaxis. Peri-ALT apraclonidine prophylaxis was not effective in patients on long-term apraclonidine, and peri-ALT pilocarpine prophylaxis tended to be less effective in patients undergoing long-term pilocarpine therapy. Pilocarpine 4% can be considered as a first-choice drug for post-ALT IOP spike prophylaxis, especially in patients under treatment with apraclonidine.

Long-term brimonidine therapy in glaucoma patients with apraclonidine allergy.

PURPOSE: To report the use of brimonidine in patients with a documented ocular allergy to apraclonidine. METHODS: We conducted a prospective, open-label study on the use of long-term brimonidine therapy in 57 patients with chronic glaucoma with documented allergy to apraclonidine. The study patients were placed on brimonidine tartrate 0.2%, 1 drop three times daily in one or both eyes, either as additive therapy to a medical regimen devoid of apraclonidine for further lowering of intraocular pressure (25 patients) or as a replacement for apraclonidine at the time of diagnosis of apraclonidine ocular allergy for maintenance of intraocular pressure control (32 patients). Clinical symptoms and signs of ocular allergy to brimonidine were monitored for up to 18 months. RESULTS: During the treatment period of up to 18 months, six (10.5%) of 57 patients developed slit-lamp biomicroscopic findings and subjective symptoms of an ocular allergic reaction that led to discontinuation of brimonidine treatment. All six patients developed ocular allergy to topical brimonidine 0.2% during the first 4 months of therapy. The addition of brimonidine 0.2% topical medication or the replacement of apraclonidine with brimonidine resulted in a significant decrease in mean intraocular pressure from 20.5+/-5.3 to 16.5+/-4.2 mm Hg (P < .0001) at the mean treatment period of 10.6+/-4.6 months (range, 0.5 to 18.0 months in all 57 patients: 5 to 18 months in the 51 patients without brimonidine allergy and 0.5 to 3.8 months in the six patients who developed brimonidine allergy. CONCLUSIONS: The incidence of ocular allergy after the use of brimonidine 0.2% topical medication for up to 18 months was 10.5% in patients with a documented history of apraclonidine allergy. Therefore, it is generally safe as well as efficacious to administer brimonidine to patients with an ocular allergy to apraclonidine.