Synthesis and X-ray structure determination of highly active Pd(II), Pd(I), and Pd(0) complexes of di(tert-butyl)neopentylphosphine (DTBNpP) in the arylation of amines and ketones.

The air-stable complex Pd(η(3)-allyl)(DTBNpP)Cl (DTBNpP = di(tert-butyl)neopentylphosphine) serves as a highly efficient precatalyst for the arylation of amines and enolates using aryl bromides and chlorides under mild conditions with yields ranging from 74% to 98%. Amination reactions of aryl bromides were carried out using 1-2 mol % Pd(η(3)-allyl)(DTBNpP)Cl at 23-50 °C without the need to exclude oxygen or moisture. The C-N coupling of the aryl chlorides occurred at relatively lower temperature (80-100 °C) and catalyst loading (1 mol %) using the Pd(η(3)-allyl)(DTBNpP)Cl precatalyst than the catalyst generated in situ from DTBNpP and Pd(2)(dba)(3) (100-140 °C, 2-5 mol % Pd). Other Pd(DTBNpP)(2)-based complexes, (Pd(DTBNpP)(2) and Pd(DTBNpP)(2)Cl(2)) were ineffective precatalysts under identical conditions for the amination reactions. Both Pd(DTBNpP)(2) and Pd(DTBNpP)(2)Cl(2) precatalysts gave nearly quantitative conversions to the product in the α-arylation of propiophenone with p-chlorotoluene and p-bromoanisole at a substrate/catalyst loading of 100/1. At lower substrate/catalyst loading (1000/1), the conversions were lower but comparable to that of Pd(t-Bu(3)P)(2). In many cases, the tri-tert-butylphosphine (TTBP) based Pd(I) dimer, [Pd(µ-Br)(TTBP)](2), stood out to be the most reactive catalyst under identical conditions for the enolate arylation. Interestingly, the air-stable Pd(I) dimer, Pd(2)(DTBNpP)(2)(µ-Cl)(µ-allyl), was less active in comparison to [Pd(µ-Br)(TTBP)](2) and Pd(η(3)-allyl)(DTBNpP)Cl. The X-ray crystal structures of Pd(η(3)-allyl)(DTBNpP)Cl, Pd(DTBNpP)(2)Cl(2), Pd(DTBNpP)(2), and Pd(2)(DTBNpP)(2)(µ-Cl)(µ-allyl) are reported in this paper along with initial studies on the catalyst activation of the Pd(η(3)-allyl)(DTBNpP)Cl precatalyst.

Factors related to corneal endothelial damage after phacoemulsification in eyes with occludable angles.

PURPOSE: To evaluate the influence of preoperative variables and early postoperative intraocular pressure (IOP) on the loss of corneal endothelial cells after phacoemulsification in eyes with occludable angles. SETTING: Taipei Veterans General Hospital, Taipei, Taiwan. METHODS: Sixty patients with occludable angles having phacoemulsification were prospectively enrolled. Corneal endothelial cell evaluation was conducted preoperatively and 3 months postoperatively. RESULTS: Three months postoperatively, the mean corneal endothelial cell density decreased by 14.5% +/- 25.8% (SD) (P < .001). Greater corneal endothelial cell loss was associated with shorter axial length (AL) (P = .008), steeper anterior corneal curvature (P = .03), greater nuclear opalescence (P = .04), and higher IOP measured 4 to 8 hours after surgery (P = .04) and the following morning (P = .002). Multiple linear regression analysis identified AL and the IOP measured 4 to 8 hours after surgery as the best predictors of postoperative corneal endothelial cell loss after adjusting for nuclear opalescence and phacoemulsification time (R2 = 0.40, P = .001). CONCLUSIONS: The corneal endothelial cell loss after phacoemulsification in eyes with occludable angles was associated with preoperative AL measurement and postoperative IOP within 24 hours. To minimize corneal endothelial cell damage, it is critical to avoid an IOP spike during the early postoperative period and to exercise extreme caution intraoperatively in eyes with an AL less than 22.6 mm.

Methylphenidate (Ritalin)-associated cataract and glaucoma.

Methylphenidate hydrochloride (Ritalin) is the drug of choice for attention deficit hyperactivity disorder (ADHD). However, an association of Ritalin with glaucoma has been reported. We report a case of Ritalin-associated cataract and glaucoma. A 10-year-old boy was diagnosed with ADHD and had received methylphenidate hydrochloride, 60 mg/day for 2 years. He presented with blurred vision. Best-corrected visual acuity was 6/60 in both eyes. Ocular examinations revealed intraocular pressure (IOP) of 30 mmHg under medication, dense posterior subcapsular opacity of lens, pale disc with advanced cupping, and marked constriction of visual field. Despite maximal anti-glaucomatous medication, IOP still could not be controlled. The patient then received combined cataract and glaucoma surgery. Visual acuity improved and IOP was within normal limits in both eyes postoperatively. Large dose of methylphenidate may cause cataract and glaucoma. The mechanism remains unclear. Doctors should be aware of the possible ocular side effects of methylphenidate.

Factors predicting intraocular pressure control after phacoemulsification in angle-closure glaucoma.

OBJECTIVES: To investigate whether the presence of glaucomatous optic neuropathy affects the reduction of intraocular pressure (IOP) after phacoemulsification in postiridotomy eyes with primary narrow angles, and to evaluate the preoperative factors associated with postoperative IOP control in primary angle-closure glaucoma (PACG). METHODS: Patients with PACG undergoing phacoemulsification were prospectively enrolled and received a complete ophthalmic examination. Diurnal IOP was measured 1 day before and 3 months after surgery. For comparison, patients with primary angle closure or angle closure suspect (PAC/S) undergoing phacoemulsification were also enrolled. RESULTS: Postoperative reduction of IOP was significant in the PACG group (n = 29; P = .001) and in the PAC/S group (n = 28; P<.001), with no significant difference between the groups. The number of glaucoma medications used decreased in both groups (both, P<.001). Multiple regression analysis for the PACG group showed that there was a positive correlation between postoperative IOP and preoperative factors of mean IOP (P = .001) and the anterior chamber depth (P = .03). CONCLUSIONS: The reduction of IOP 3 months after phacoemulsification is significant and is similar in extent in postiridotomy eyes with and without glaucomatous optic neuropathy. A higher postoperative IOP in PACG is associated with a higher preoperative IOP and with a deeper preoperative anterior chamber depth.

Bulky alkylphosphines with neopentyl substituents as ligands in the amination of aryl bromides and chlorides.

Di(tert-butyl)neopentylphosphine (DTBNpP) in combination with palladium sources provided catalysts with comparable or better activity for the Hartwig-Buchwald amination of aryl bromides than tri(tert-butyl)phosphine (TTBP) under mild conditions. DTBNpP also provided effective catalysts for amination reactions of aryl chlorides at elevated temperatures. Further replacement of tert-butyl groups with neopentyl substituents resulted in less effective ligands for amination reactions. Computationally derived cone angles showed that replacement of a tert-butyl group with a neopentyl group significantly increased the cone angle of the phosphine. The larger cone angle of DTBNpP than TTBP appears to correlate with the higher activity of catalysts derived from DTBNpP in the amination of aryl bromides. TTBP is a stronger electron donor than DTBNpP, which may explain the higher activity for TTBP-derived catalysts toward aryl chlorides.

Intraocular pressure measured with a noncontact tonometer in an elderly Chinese population: the Shihpai Eye Study.

OBJECTIVE: To determine the distribution of intraocular pressure (IOP) as measured by a noncontact tonometer (NCT) and risk factors responsible for ocular hypertension in elderly Chinese people. DESIGN: Population-based study of randomly sampled Chinese people 65 years and older in Shihpai, Taipei, Taiwan. MAIN OUTCOME MEASURES: Participants completed an interview and underwent a physical examination and a standardized ophthalmic examination, including IOP measurement with the NCT. People with a history of glaucoma were excluded. Risk factors were assessed using multivariate regression analysis. RESULTS: Of 1361 study participants examined, 1292 (95.4%) had no history of glaucoma and were therefore included in the study. Their mean +/- SD IOP was 12.9 +/- 3.1 mm Hg. The IOP decreased significantly (P<.001) with age, changing from 13.3 +/- 3.0 mm Hg in participants aged 65 to 69 years to 11.6 +/- 2.8 mm Hg in those 80 years and older. Women had significantly higher IOP than men (P<.001). In the multivariate regression analysis, decreasing age, female sex, increasing systolic blood pressure, a history of diabetes, and alcohol drinking were significantly associated with increasing IOP. CONCLUSIONS: The distribution of IOP in elderly Chinese people is similar to that found in other East Asian people, with a negative age-IOP relationship. The mean IOP values in this elderly Chinese population were lower than in white people but higher than in Japanese people in similarly aged groups. Establishing the epidemiologic characteristics of IOP with the NCT is important for the mass screening of ocular hypertension.

A retrospective analysis of the stability and relapse of soft and hard tissue change after bilateral sagittal split osteotomy for mandibular setback of 64 Taiwanese patients.

PURPOSE: This study was an analysis of the soft and hard tissue changes of the facial profile after bilateral sagittal splitting osteotomy for mandibular setback of Taiwanese patients. PATIENTS AND METHODS: We collected pre- and postsurgical lateral cephalographs of 64 patients (28 males, 36 females) with skeletal Class III malocclusion who received combined orthodontic-surgical treatment with bilateral sagittal splitting osteotomy mandibular setback at Taipei Veterans General Hospital between 1994 and 2000. Nineteen cephalometric parameters of (14 linear, 4 angular, and the BS index) soft and hard tissues were measured at 1 week before treatment, and 2 months and 1 year after surgery, and analyzed by paired t test. RESULTS: Mean patient age was 20.0 +/- 1.6 years. The patients underwent an average of 7 mm mandibular setback at the osseous pogonion (Pog). Average setbacks at Pog and soft tissue pogonion (pog) were 5.54 mm and 4.85 mm, respectively, at 1 year after surgery. The setback ratio of Pog/pog was 1:0.88. The hard tissue relapse at Pog was 21% at 1 year after surgery. Improvement in prognathic profile was demonstrated by significant changes in the positions of Pog and pog, ANB angle, the distance from lower lip to esthetic line (E-L lip), and the BS index after surgery. However, compared with parameters obtained from a normal Taiwanese population, the cephalometric data of Pog, pog, and BS index still indicated mild prognathism. CONCLUSION: Although mandibular prognathism could be grossly improved by bilateral sagittal splitting osteotomy mandibular setback, a significant amount of relapse occurred within 1 year after surgery. The extent of the postoperatively preserved features showing mandibular prognathism should be a concern for both patients and physicians.

Cannabinoid receptors and T helper cells.

We have reported that injection of marijuana cannabinoids, such as Delta(9)-tetrahydrocannabinol (THC), into mice, followed by infection with Legionella pneumophila (Lp), suppresses the development of cell-mediated immunity T helper 1 (Th1) activity. These effects are accompanied by suppression of interleukin (IL)-12 and interferon (IFN) gamma production and enhancement of IL-4 production suggesting THC-induced T helper cell biasing. In the current report, other T helper cell biasing mechanisms were studied. Mice were injected with THC followed 18 h later by a challenge infection with Lp. Two-hour post-infection, spleens were removed and analyzed for mRNA to either IL-12Rbeta2 or GATA3 gene products. The results showed that THC suppressed IL-12Rbeta2 but increased GATA3. Receptor antagonists for CB1 (SR141716A, SR1) and CB2 (SR144528, SR2) were also injected to analyze the involvement of cannabinoid receptors. It was determined that SR1 attenuated the THC suppression of IL-12Rbeta2, while SR2 attenuated the increase in GATA3 mRNA. These results suggest that THC suppresses Th1 biasing activity such as IL-12Rbeta2 by a CB1 mediated mechanism and enhances the Th2 biasing activity, GATA3, by a CB2 mechanism. This dichotomy of receptor involvement might result from differential expression and/or signaling function of CB1 and CB2 on Th1 and Th2 cells.

Patterns of visual field defects in chronic angle-closure glaucoma with different disease severity.

PURPOSE: To evaluate the patterns of visual field defects in patients with chronic angle-closure glaucoma (CACG) with varying extent of optic nerve damage. DESIGN: Prospective, consecutive, observational case series. PARTICIPANTS: One hundred forty-six Asian patients with well-controlled CACG. METHODS: Visual field tests were performed using program 24-2 of the Humphrey Field Analyzer (Humphrey Instruments, San Leandro, CA) with the Swedish interactive thresholding algorithm standard. One hundred ten eligible visual fields were scored with the system adopted by the Advanced Glaucoma Intervention Study and were categorized into 4 groups accordingly: mild, moderate, severe, and end-stage. Each hemifield was divided into the nasal, paracentral, and arcuate areas, and field loss that involved respective areas was defined as nasal step, paracentral scotoma, and arcuate scotoma. MAIN OUTCOME MEASURES: The distribution of field defect patterns in each group was evaluated. The mean deviation (MD) was compared among the 3 areas within one hemifield and between each pair of corresponding areas across the median raphe. RESULTS: The nasal area was the most commonly damaged area in the mild group, being noted in 52% of eyes in the superior hemifield and 58% of eyes in the inferior hemifield. In the moderate group, field loss involving both the nasal and arcuate areas dominated the superior hemifield, whereas field loss involving all three areas dominated the inferior hemifield. The MD of the nasal area was the worst among the three areas in each hemifield of the mild and moderate groups, as well as in the inferior hemifield of the severe group (all P < 0.001). There were no significant differences in the MD of each area between the superior hemifield and their inferior counterparts. However, the superior hemifield as a whole showed a better MD than the inferior hemifield (P=0.034) in the mild group. CONCLUSIONS: Visual field loss that involved the nasal area was the most common pattern in the early stage of CACG. The MD of the nasal area was worse than those of the arcuate and the paracentral areas within the same hemifield in the mild, moderate, and severe groups of CACG patients.

The efficacy and safety of brimonidine 0.2% compared with timolol 0.5% in glaucoma: a randomized clinical trial on Taiwanese patients.

BACKGROUND: Brimonidine is a highly selective alpha-2 adrenergic receptor agonist with intraocular pressure (IOP) reducing effect. We conducted this study in Taiwan to compare the safety and efficacy ofbrimonidine 0.2% with timolol 0.5% for the treatment of glaucoma. METHODS: A prospective, randomized, single-masked, 1-month clinical efficacy and safety trial was conducted from March to September 2000. Forty glaucoma patients were enrolled--29 in the brimonidine group and 11 in the timolol group. Patients instilled their study medications twice daily for 4 weeks, and were followed at baseline visit, weeks 2 and 4. Demographic data, reduction of IOP, safety and adverse events were obtained and analyzed. RESULTS: Both drugs showed sustained ocular hypotensive efficacy in the study period. At baseline, the mean IOP was 24.48 +/- 2.29 mmHg in the brimonidine group and 23.32 +/- 0.82 mmHg in the timolol group. The IOP readings after treatment were significantly lower than their baseline levels in both groups at all visits (p < 0.001). At peak, the mean decreases from the baseline IOP ranged from 5.22 +/- 0.30 mmHg to 6.96 +/- 0.33 mmHg for brimonidine and from 4.55 +/- 0.49 mmHg to 6.64 +/- 0.53 mmHg for timolol. At trough, the mean decreases from baseline ranged from 3.72 +/- 0.32 mmHg to 4.55 +/- 0.32 mmHg for brimonidine and 3.82 +/- 0.52 mmHg to 4.27 +/- 0.51 mmHg for timolol. No significant between-group differences were seen at peak or trough at all visits. The clinical success rate was 86.2% in the brimonidine group and 81.8% in the timolol group, making no statistically significant difference between them (p = 0.817). 17.2% of patients in brimonidine group and 9.0% patients in timolol group reported mild adverse events. Ocular allergy occurred in 10.3% of patients in brimonidine group. No significant changes in visual acuity, biomicroscopy or ophthalmoscopy were observed in both groups. Mean systolic and diastolic blood pressure remained relatively stable in both groups except in week 2 (p = 0.016) when brimonidine had lower systolic blood pressure. However, brimonidine showed no significant difference in week 4 from baseline. The mean heart rate in the brimonidine group was relatively unchanged over the study period. Patients receiving timolol experienced statistically significant mean heart rate decreases from baseline (p = 0.020) in week 4. CONCLUSIONS: Topically applied twice daily for one month, brimonidine tartrate 0.2% has clinical effectiveness equivalent to timolol 0.5% in Taiwanese patients with glaucoma. It has a safe systemic profile with minimum effect on the heart.

Changes in intraocular pressure and ocular perfusion pressure after latanoprost 0.005% or brimonidine tartrate 0.2% in normal-tension glaucoma patients.

OBJECTIVE: To evaluate and compare the effects of latanoprost 0.005% once daily and brimonidine tartrate 0.2% twice daily in patients with normal-tension glaucoma (NTG). DESIGN: A randomized, open-label, crossover study. PARTICIPANTS: Twenty-eight NTG patients with progressive visual field defects/optic disc excavation, new disc hemorrhage, or field defects that threatened fixation. INTERVENTION: Patients were randomly allocated to one of two groups. Patients in group 1 were treated with latanoprost, lubricant, and brimonidine for 4 weeks each, whereas patients in group 2 were treated with brimonidine, lubricant, and latanoprost for 4 weeks each. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), pulse rate, and blood pressure were measured at 8 am, 12 noon, and 4 pm after each 4-week treatment. Ocular perfusion pressure (OPP) was calculated. RESULTS: Latanoprost and brimonidine reduced the average IOP by 3.6 +/- 1.9 mmHg (P < 0.001) and 2.5 +/- 1.3 mmHg (P < 0.001), respectively, with a significant difference between the two regimens (P = 0.009). Both drugs significantly reduced IOP at each time point. Latanoprost decreased IOP significantly more than did brimonidine at 8 am (11.7 +/- 2.2 mmHg vs. 13.7 +/- 2.1 mmHg, P = 0.004) and 4 pm (11.4 +/- 2.1 mmHg vs. 13.2 +/- 2.9 mmHg, P = 0.004), but IOP was equal between the two agents at 12 noon (11.5 +/- 2.6 mmHg vs. 11.5 +/- 2.3 mmHg, P = 0.967). IOP was maintained at 12 mmHg or lower in 18 (66.7%) of 27 patients after treatment with latanoprost and in 9 (33.3%) of 27 patients after treatment with brimonidine. Latanoprost monotherapy reduced IOP by 30% in 8 patients (29.6%), but brimonidine monotherapy did not reduce IOP by that much in any of the patients. OPP increased after latanoprost treatment (P < 0.001) but did not increase after brimonidine treatment (P = 0.355). There was no significant change in pulse rate or blood pressure. CONCLUSIONS: Both latanoprost and brimonidine reduce IOP in NTG patients. Brimonidine has a peak IOP-lowering effect equal to that of latanoprost but produces a higher mean diurnal IOP than does latanoprost because of its shorter effect. Latanoprost might favorably alter optic disc blood perfusion by increasing OPP.

Use of latanoprost to reduce acute intraocular pressure rise following neodymium: Yag laser iridotomy.

PURPOSE: To evaluate the efficacy of latanoprost in reducing acute intraocular pressure (IOP) elevation after neodymium:Yag laser iridotomy (LI). METHODS: Primary angle-closure glaucoma (PACG) eyes were randomized to receive premedication with latanoprost and pilocarpine or with pilocarpine only before LI. Postoperative IOP changes were compared with Wilcoxon signed-ranks test using the fellow eyes of 47 patients who had one eye in each group. RESULTS: Postoperative pressure spikes were significantly lower (p = 0.010) in the latanoprost group (4.1 +/- 5.0 mmHg) than in the control group (6.7 +/- 7.0 mmHg). Mean elevation of IOP was less in the latanoprost group than in the control group at 1 hour (2.5 +/- 4.8 versus 4.1 +/- 4.7 mmHg, p = 0.013) and 2 hours (0.8 +/- 5.6 versus 4.4 +/- 8.1 mmHg, p = 0.003) postoperatively. Eleven eyes in the latanoprost group (23.4%) and 20 eyes in the control group (42.6%) developed a rise in IOP > or = 6 mmHg (p = 0.048). CONCLUSION: Latanoprost may reduce the pressure rise following LI in PACG eyes, but its application is limited by a late onset of effect.

Comparisons of risk factors and visual field changes between juvenile-onset and late-onset primary open-angle glaucoma.

PURPOSE: To identify the differences in risk factors and visual field (VF) changes between juvenile primary open-angle glaucoma (JOAG) and late-onset chronic open-angle glaucoma (COAG). METHODS: The demographic and presenting clinical data of 27 JOAG and 30 COAG patients were retrospectively reviewed. Comparisons between the two groups were performed using Mann-Whitney U test, Wilcoxon signed-rank test, and Fisher's exact test. RESULTS: A family history of glaucoma (37%) and a history of steroid usage (14.8%) were identified in JOAG patients only. The JOAG patients had a longer axial length (p < 0.001) and more often a myopic refractive state (p < 0.001) than the COAG patients. Patients with COAG showed a deeper (p = 0.016) and a more extensive (p = 0.008) defect in the superior than in the inferior hemifield, as well as a deeper (p = 0.016) and a more extensive (p = 0.001) defect in the superior than in the inferior arcuate area, while JOAG patients showed symmetric VF defects between the superior and inferior hemifields. Purely diffuse VF depression is more common in JOAG than in COAG patients (p = 0.03). CONCLUSIONS: JOAG patients demonstrated more axial myopic changes than patients with COAG as well as a pattern of superior-inferior symmetric VF defects. Axial myopia may play a critical role in the pathogenesis of JOAG.