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Biomedical subjects

J A Stewart

Publications and source records attributed to J A Stewart.

At least 19 recordsLinked to original sources

A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses.

BACKGROUND: Teriflunomide, a dihydro-orotate dehydrogenase inhibitor, has immunomodulatory effects, including the ability to suppress experimental allergic encephalomyelitis. In this randomized, double-blind, placebo-controlled Phase II study, the authors examined the safety and efficacy of oral teriflunomide in multiple sclerosis (MS) with relapses. METHODS: Patients (n = 179) with relapsing-remitting MS (n = 157) or secondary progressive MS with relapses (n = 22) were randomized to receive placebo, teriflunomide 7 mg/day, or teriflunomide 14 mg/day for 36 weeks. MRI brain scans were performed every 6 weeks. The primary endpoint was the number of combined unique active lesions per MRI scan. Secondary endpoints included MRI-defined disease burden, relapse frequency, and disability increase. RESULTS: The median number of combined unique active lesions per scan was 0.5, 0.2, and 0.3 in the placebo, teriflunomide 7 mg/day (p < 0.03 vs placebo), and teriflunomide 14 mg/day (p < 0.01 vs placebo) groups during the 36-week double-blind treatment phase. Teriflunomide-treated patients also had significantly fewer T1 enhancing lesions per scan, new or enlarging T2 lesions per scan, and new T2 lesions. Patients receiving teriflunomide 14 mg/day had significantly reduced T2 disease burden. Teriflunomide treatment resulted in trends toward a lower annualized relapse rate and fewer relapsing patients (14 mg/day only) vs placebo. Significantly fewer patients receiving teriflunomide 14 mg/day vs placebo demonstrated disability increase. Treatment was well tolerated; numbers of adverse events and serious adverse events were similar in all treatment groups. CONCLUSION: Oral teriflunomide was effective in reducing MRI lesions and was well tolerated in patients with relapsing multiple sclerosis.

Adult↗

The clinical validity of the treatment satisfaction survey for intraocular pressure in ocular hypertensive and glaucoma patients.

PURPOSE: To provide initial validation of the Treatment Satisfaction Survey-Intraocular Pressure (TSS-IOP) quality-of-life survey that analyses specific issues related to side effects, patient satisfaction, and compliance. METHODS: A prospective, observational cohort of 250 consecutive patients with primary open-angle glaucoma or ocular hypertension was administered the TSS-IOP survey. RESULTS: Factors that correlated with patient satisfaction included perceived effectiveness of the medicine (F=7.47, P<0.001), ocular irritation (F=6.06, P<0.001), conjunctival hyperaemia (F=4.40, P<0.001), ease of use (F=8.52, P<0.001), and convenience of use (F=6.90, P<0.001). Patient compliance, acceptance of their illness, and knowledge of glaucoma were also related to perceived effectiveness of the medicine (P<0.001), ease of use (P<0.05) and convenience (P<0.001). Physician ratings of patient pressure control, side effects, and instillation problems also were significantly correlated to patient satisfaction (R=0.13-0.26, P=0.05-0.001). The physician ratings of patient compliance, however, were not significantly related to any dimension of patient satisfaction (P>0.05). Among monotherapy prostaglandin treatments, latanoprost demonstrated statistically greater satisfaction than bimatoprost or travoprost regarding conjunctival hyperaemia (P<0.05) and eye irritation (P<0.01). CONCLUSIONS: This study provides initial evidence that patient satisfaction may be related to compliance, perceived effectiveness of treatment, adverse side effects, ease and convenience of use, acceptance of illness, and knowledge of glaucoma.

Aged↗

A randomized trial of adding insulin glargine vs. avoidance of insulin in people with Type 2 diabetes on either no oral glucose-lowering agents or submaximal doses of metformin and/or sulphonylureas. The Canadian INSIGHT (Implementing New Strategies with Insulin Glargine for Hyperglycaemia Treatment) Study.

AIMS: Insulin is generally withheld until people with Type 2 diabetes are unresponsive to other therapies. However, its potential advantages suggest that it could be added earlier to achieve glycaemic goals; this possibility was tested in a clinical trial. METHODS: Consenting adults aged 18-80 years with Type 2 diabetes for at least 6 months, HbA1c of 7.5-11%, and on 0, 1 or 2 oral agents, were randomized to one of two therapeutic approaches for 24 weeks: evening insulin glargine plus self-titration by 1 unit/day if the fasting plasma glucose (FPG) was > 5.5 mmol/l; or conventional therapy with physician adjustment of oral glucose-lowering agents if capillary FPG levels were > 5.5 mmol/l. The primary outcome was the first achievement of two consecutive HbA1c levels <or= 6.5%. RESULTS: Two hundred and six participants were allocated to glargine and 199 to oral agents. Compared with control subjects, participants receiving glargine: (i) were 1.68 times more likely to achieve two consecutive HbA1c levels <or= 6.5% (95% CI 1.00-2.83; P = 0.049); (ii) reduced their HbA1c by 1.55 vs. 1.25% (P = 0.005), achieving adjusted means of 7.0 vs. 7.2% (P = 0.0007); (iii) had lower FPG (P = 0.0001), non-high-density lipoprotein (HDL) cholesterol (P = 0.02) and triglycerides (P = 0.02); (iv) had greater increases in treatment satisfaction (P = 0.045); and (v) had a 1.9-kg greater increase in weight (P < 0.0001). No differences in hypoglycaemia were noted. CONCLUSIONS: Adding insulin glargine is more likely to achieve a lower HbA(1c) level than conventional therapy with oral agents.

Adolescent↗

Carriage, quantification, and predominance of methanogens and sulfate-reducing bacteria in faecal samples.

AIMS: To determine carriage rates and densities of methanogens and sulfate-reducing bacteria in adults and children using molecular methods, and to also determine if a reciprocal relationship exists between these organisms. METHODS AND RESULTS: Real-time PCR was used to detect and quantify methanogens and sulfate-reducing bacteria. Real-time PCR was more sensitive than breath methane measurements. Real-time PCR assays were applied to faecal DNA samples collected from 40 children and 12 adults. Methanogens were present in 25% of the children and 42% of the adults studied, and sulfate-reducing bacteria were detected in 15% of the children and 58% of the adults. High levels of sulfate-reducing bacteria were found in two methanogenic adults. CONCLUSIONS: Carriage rates and densities of methanogens and sulfate-reducing bacteria are greater in adults than in children. Competition does not necessarily lead to the predominance of one group in the faecal microflora. SIGNIFICANCE AND IMPACT OF THE STUDY: This study describes sensitive, molecular assays that could be used to monitor these organisms in gastrointestinal disease. Therapeutic exclusion of one group from the bowel would not necessarily lead to the expansion of the other, as there does not appear to be a reciprocal relationship between these groups.

Adult↗

Recruitment of sperm donors: the Newcastle-upon-Tyne experience 1994-2003.

BACKGROUND: The demand for sperm donors has continued despite the introduction of ICSI. This study was undertaken in the light of impending changes in donor anonymity laws to evaluate the recruitment process of sperm donors. METHODS: Retrospective analysis of 1101 potential sperm donors in a tertiary referral centre between January 1994 and August 2003. The main outcome measures were to determine the demographic details, recruitment rate and reasons for rejection of donors. RESULTS: The majority of the applicants were aged <36 years (88.07%), students (54.88%), without a partner (53.47%), unmarried (85.38%) and without proven fecundity (78.67%). Only 3.63% of the applicants were released as donors, 30.79% defaulted, whilst 64.48% were rejected. The most common reason for rejection was suboptimal semen quality (85.07%). Over the years, the numbers of the applicants and released donors have declined significantly. The overall clinical pregnancy rate from donor sperm during this period was 23.52%. CONCLUSIONS: In this successful anonymous sperm donor programme only a small proportion of the applicants are released as donors. The significant decline in released sperm donors coupled with the potential effects of loss of donor anonymity means that new strategies for sperm donor recruitment are urgently required.

Adult↗

Brimonidine 0.2% vs unoprostone 0.15% both added to timolol maleate 0.5% given twice daily to patients with primary open-angle glaucoma or ocular hypertension.

PURPOSE: To compare the efficacy and safety of brimonidine 0.2% vs unoprostone 0.15%, both added to timolol maleate 0.5% each given twice daily. METHODS: In this prospective, multi-centred, double-masked, crossover comparison, patients were randomized to one treatment group for a 6-week treatment period, and then crossed over to the opposite treatment. Measurements were performed at 0800, 1000, 1600, 1800, and 2000 h at baseline and at the end of each treatment period. RESULTS: In all, 33 patients entered this trial and 29 completed. The baseline trough intraocular pressure (IOP) was 23.3+/-2.4 and the diurnal curve IOP was 22.0+/-1.3 mmHg. For the brimonidine and timolol maleate treatment group, the trough IOP was 21.6+/-3.3 and the diurnal curve IOP was 19.8+/-2.1 mmHg, while the timolol and unoprostone treatment showed a trough IOP of 20.9+/-3.8 and a diurnal curve IOP of 19.3+/-2.4 mmHg. There was no significant difference between treatment groups at any time point for the diurnal curve, or in the reduction from baseline (P>0.05). Both treatments failed to statistically reduce the IOP from baseline at 1800 h. There was no difference between treatment groups regarding ocular and systemic unsolicited adverse events, but patients admitted to more dryness (P=0.02) and burning upon instillation (P<0.0001) with unoprostone by survey. CONCLUSION: Brimonidine 0.2% or unoprostone 0.15% added to timolol maleate 0.5% provide similar efficacy and safety throughout the daytime diurnal curve.

Antihypertensive Agents↗

Comparison of human herpesvirus 8 and Epstein-Barr virus seropositivity among children in areas endemic and non-endemic for Kaposi's sarcoma.

Human herpesvirus 8 (HHV-8) is the etiologic agent of Kaposi's sarcoma (KS). Several studies indicate horizontal HHV-8 transmission among children in areas where KS is endemic, but few studies have assessed acquisition of HHV-8 by children in low seroprevalence areas. Antibody screening was carried out for HHV-8 and Epstein-Barr virus (EBV) on 787 serum specimens from children living in two areas where HHV-8 is not endemic, the United States (US) and Germany, and on 184 specimens from children living in a KS-endemic area (Nigeria). For children in the US and Germany, the results showed low HHV-8 seroprevalence rates (3-4%). However, US children aged 6 months to 5 years had higher HHV-8 antibody titers than did 6-17-year-old children (P < 0.01), a finding consistent with more recent infections being detected in the younger children. Compared with seroprevalence rates and antibody titers in US and German children, those in Nigerian children were significantly higher, and seroprevalence increased with age. There was no evidence of cross-reactivity between assays for HHV-8 and EBV, despite the genetic similarity of these two herpesviruses. The data indicate that HHV-8 transmission among children where HHV-8 is not endemic occurs, but is uncommon. The findings also suggest that HHV-8 antibodies, as measured by current tests, may not persist for long periods in populations at low risk for KS and that vertical transmission is rare, although longitudinal studies are necessary to address directly these issues.

Adolescent↗

Short-term ocular tolerability of dorzolamide 2% and brinzolamide 1% vs placebo in primary open-angle glaucoma and ocular hypertension subjects.

PURPOSE: To compare ocular tolerability of dorzolamide 2%, brinzolamide 1%, and placebo given three times daily. METHODS: A prospective, double-masked, three-centre, crossover comparison in which 25 ocular hypertensive or primary-open angle glaucoma subjects were randomized to receive dorzolamide, brinzolamide, or placebo three times daily for 3 days. Intraocular pressure, visual acuity, a visual analogue scale, and ocular and systemic symptom queries were completed at the end of each period. RESULTS: After chronic dosing, there was a significant difference in ocular pain on the visual analogue scale among the groups at the 10-s postinstillation time point with dorzolamide having the highest level (22.5+/-28.9) compared to brinzolamide (5.0+/-8.7) or placebo (3.2+/-10.4) (P=0.0006). No differences between groups were observed preinstillation nor following dosing at 3 or 10-min postinstillation. On the initial instillation, the 10-s postinstillation pain was rated as 43.3+/-77.1, which was significantly higher than after chronic dosing (P=0.017). On the ocular symptom query, dorzolamide had the highest incidence of burning/stinging and redness compared to the other groups, but was generally characterized as mild. There were no significant differences in the visual acuity at any time point. CONCLUSIONS: This study suggests that subjects treated with dorzolamide suffer more ocular pain upon instillation compared to brinzolamide or placebo. However, pain symptoms are fewer following chronic dosing and are generally characterized as mild.

Adult↗

Efficacy and safety of the latanoprost/timolol maleate fixed combination vs concomitant brimonidine and latanoprost therapy.

AIMS: To evaluate the efficacy and safety of latanoprost/timolol maleate fixed combination (LTFC) given once daily vs the concomitant therapy of brimonidine twice daily and latanoprost once daily in primary open-angle glaucoma or ocular hypertensive subjects. METHODS: A prospective, double-masked, active-controlled comparison in which qualified subjects had all glaucoma medicines discontinued for 1 month and then were randomized to either LTFC or brimonidine and latanoprost concomitant therapy for 6 weeks. They were then switched to the other treatment regimen. The intraocular pressure (IOP) was measured at 0800, 1200, and 1600 h at baseline and at the end of Periods 1 and Period 2. RESULTS: In 32 subjects, the diurnal curve of the untreated IOP of 26.0+/-3.4 decreased to 17.8+/-2.5 on LTFC and 17.2+/-2.8 mmHg on brimonidine and latanoprost (P=0.31). At 0800 and 1600 h, the IOPs were statistically similar between the groups (P>0.05). At 1200 h the latanoprost and brimonidine treatment IOP was statistically lower (16.2+/-3.2) than LTFC (18.0+/-2.8 mmHg). However, the reduced IOP from untreated baseline was not statistically different at each time point and for the diurnal curve for each therapy (P<0.05). Safety was similar between groups for both solicited and unsolicited side effects (P>0.05). CONCLUSION: This study suggests that LTFC and concomitant therapy of brimonidine and latanoprost provide statistically similar diurnal IOP reduction from an untreated baseline.

Aged↗

Daytime diurnal curve comparison between the fixed combinations of latanoprost 0.005%/timolol maleate 0.5% and dorzolamide 2%/timolol maleate 0.5%.

PURPOSE: The diurnal efficacy and safety of the fixed combinations of latanoprost/timolol given once daily vs dorzolamide/timolol given twice daily in primary open-angle glaucoma or ocular hypertensive patients. DESIGN: A double-masked, two-centre, crossover comparison. RESULTS: In 33 patients, the mean diurnal IOP (0800-2000, measured every 2 h) for latanoprost/timolol fixed combination was 17.3+/-2.2 mmHg and for dorzolamide/timolol, the fixed combination was 17.0+/-2.0 mmHg (P = 0.36). Additionally, there was no statistical difference for individual time points following a Bonferroni correction. A bitter taste was found more frequently with the dorzolamide/timolol fixed combination (n = 6) than the latanoprost/timolol fixed combination (n = 0) (P = 0.040), while the latanoprost/timolol fixed combination demonstrated more conjunctival hyperaemia (n = 9) than the dorzolamide/timolol fixed combination (n = 2) (P = 0.045). One patient was discontinued early from the dorzolamide/timolol fixed combination due to elevated IOP. CONCLUSION: This study suggests that the daytime diurnal IOP is not statistically different between the dorzolamide/timolol fixed combination and latanoprost/timolol fixed combination in primary open-angle glaucoma and ocular hypertensive patients.

Adult↗

Brimonidine purite 0.15% versus dorzolamide 2% each given twice daily to reduce intraocular pressure in subjects with open angle glaucoma or ocular hypertension.

BACKGROUND/AIMS: To evaluate the efficacy of brimonidine purite versus dorzolamide given twice daily in primary open angle glaucoma or ocular hypertensive subjects. METHODS: In this double masked, multicentre, prospective, crossover comparison 33 subjects were randomised to brimonidine purite or dorzolamide for the first 4 week treatment period after a 4 week washout. Subjects began the opposite treatment for the second 4 week period after another 4 week washout. Intraocular pressure (IOP) was measured at 08:00 (trough) and 10:00, 18:00, and 20:00 hours after dosing at each baseline and at the end of each treatment period. RESULTS: The baseline diurnal IOP was 22.9 (SD 2.8) for brimonidine purite and 22.2 (SD 2.4) mm Hg for dorzolamide. The trough IOP following 4 weeks of therapy was 21.0 (SD 3.7) for brimonidine purite and 21.0 (SD 3.1) mm Hg for dorzolamide (p = 0.90). The mean diurnal IOP was 19.3 (SD 3.1) for brimonidine purite and 19.8 (SD 2.4) mm Hg for dorzolamide (p = 0.46). Dorzolamide caused more ocular stinging upon instillation (n = 8) than brimonidine purite (n = 1) (p = 0.02). No statistical differences existed between groups for systemic adverse events. CONCLUSIONS: This study suggests that brimonidine purite and dorzolamide each given twice daily have similar efficacy in primary open angle glaucoma or ocular hypertensive subjects. However, a trend was observed at 10:00 of greater brimonidine purite efficacy compared with dorzolamide.

Antihypertensive Agents↗

Altering behavioral responses and dopamine transporter protein with antisense peptide nucleic acids.

The dopamine transporter (DAT) plays a role in locomotion and is an obligatory target for amphetamines. We designed and synthesized an antisense peptide nucleic acid (PNA) to rat DAT to examine the effect of this antisense molecule on locomotion and on responsiveness to amphetamines. Rats were injected intraperitoneally daily for 9 days with either saline, an antisense DAT PNA, a scrambled DAT PNA, or a mismatch DAT PNA. On days 7 and 9 after initial motility measurements were taken, the animals were challenged with 10 mg/kg of amphetamine and scored for motility. On day 7, there was no significant difference between the baseline levels of activity of any of the groups or their responses to amphetamine. On day 9, the antisense PNA-treated rats showed a statistically significant increase in their resting motility (P < 0.01). When these rats were challenged with amphetamine, motility of the saline-, scrambled PNA-, and mismatch PNA-treated animals showed increases of 31-, 36-, and 20-fold, respectively, while the antisense PNA-treated animals showed increases of only 3.4-fold (P < 0.01). ELISA results revealed a 32% decrease in striatal DAT in antisense PNA-treated rats compared with the saline, scrambled PNA, and mismatch PNA controls (P < 0.001). These results extend our previous findings that brain proteins can be knocked down in a specific manner by antisense molecules administered extracranially. Additionally, these results suggest some novel approaches for the treatment of diseases dependent upon the function of the dopamine transporter.

Animals↗

Intraperitoneal injection of antisense peptide nucleic acids targeted to the mu receptor decreases response to morphine and receptor protein levels in rat brain.

To determine the effectiveness of peptide nucleic acids (PNAs) in vivo, we designed and synthesized PNAs antisense to the mu receptor, the molecular target of morphine for inducing antinociception. Responsiveness of rats to morphine and the levels of mu receptor expression after treatment was measured. We delivered intraperitoneal injections of antisense PNAs targeted to the mu receptor (AS-MOR), mismatch PNAs (AS-MOR MM), antisense PNAs targeted to the neurotensin receptor subtype 1 (AS-NTR1), or saline and then challenged the rats with 5 mg/kg morphine (intraperitonally) or neurotensin directly into the periaqueductal gray region of the brain. To avoid tolerance, separate groups of animals were tested at 24, 48, and 72 h post-PNA treatment. Only animals treated with the AS-MOR showed a reduction in their antinociceptive response to morphine. The lack of effect of morphine on the AS-MOR rats was profound at 24 and 48 h, but animals tested at 72 h were similar to control groups. At 24 h the AS-MOR rats had a significant 55% decrease in the levels of mu receptor in their periaqueductal gray region, while AS-MOR MM rats showed no significant change. Lastly, the AS-MOR rats continued to show a normal antinociceptive response to neurotensin. This study, therefore, provides additional support for the use of PNAs to target proteins within brain by systemically administered PNAs.

Analgesics, Opioid↗

Additive efficacy of unoprostone isopropyl 0.12% (rescula) to latanoprost 0.005%.

PURPOSE: To evaluate the safety and efficacy of adding unoprostone isopropyl 0.12% vs placebo both given twice daily to latanoprost 0.005% given every evening. METHODS: We treated 41 patients with primary open-angle glaucoma or ocular hypertension with latanoprost 0.005% for 1 month and then randomized each to either placebo or unoprostone isopropyl 0.12% for 8 weeks. Diurnal intraocular pressures were measured at 08:00, 10:00, 12:00, 18:00, and 20:00 hours, both at baseline (time of randomization) and after 8 weeks of treatment. RESULTS: Twenty patients were treated in the placebo group and 21 in the unoprostone isopropyl group. After 8 weeks of treatment in the placebo group, the trough intraocular pressure at 08:00 and the diurnal pressure were 20.4 +/- 3.2 and 19.1 +/- 2.2 mm Hg, respectively. In the unoprostone isopropyl group the pressures were 19.4 +/- 3.3 and 18.0 +/- 1.7 mm Hg (P =.22 and P =.042), respectively. However, eyes with a baseline pressure of 22 mm Hg or greater on latanoprost had an average 3.3 mm Hg greater reduction at trough (P <.01) and a 2.1 mm Hg greater decrease in diurnal pressure (P =.030) after adding unoprostone isopropyl (n = 14 eyes) compared with placebo (n = 16 eyes; P <.001). In addition, the range of the pressures throughout the diurnal curve was reduced from 2.7 mm Hg on latanoprost alone to 1.4 mm Hg after adding unoprostone isopropyl. Adverse events were similar between groups, and no patients were discontinued because of safety reasons. CONCLUSIONS: This study suggests that unoprostone isopropyl can safely improve the diurnal curve characteristics in patients who continue to have an elevated pressure on latanoprost 0.005% alone.

Antihypertensive Agents↗

The efficacy and safety of latanoprost 0.005% once daily versus brimonidine 0.2% twice daily in open-angle glaucoma or ocular hypertension.

PURPOSE: To evaluate the efficacy and safety of latanoprost 0.005% given topically every evening versus brimonidine 0.2% given topically twice daily in primary open-angle glaucoma or ocular hypertensive patients. METHODS: This was a multicenter, crossover, double-masked comparison. After a 28-day treatment-free period, patients with primary open-angle glaucoma or ocular hypertension were randomized for 6 weeks to brimonidine or latanoprost and then crossed over to the opposite treatment. At baseline and after each treatment period, patients underwent intraocular pressure measurements every 2 hours from 08:00 to 20:00. RESULTS: In 33 patients the mean baseline trough (08:00) was 23.2 +/- 2.1 mm Hg and the diurnal curve pressure was 19.8 +/- 2.7 mm Hg. The trough and diurnal intraocular pressures for brimonidine were 19.6 +/- 3.4 mm Hg and 17.6 +/- 2.2 mm Hg, respectively. Brimonidine statistically reduced the pressure from baseline at each time point except hours 10 and 12 (P =.14 and P =.21, respectively). For latanoprost, the trough and diurnal pressures were 16.2 +/- 2.9 mm Hg and 15.4 +/- 2.5 mm Hg, respectively, and the pressure was statistically reduced at each time point (P <.001) and for the diurnal curve (P <.001). When compared directly, the intraocular pressure level for latanoprost was lower than brimonidine for the diurnal pressure and at each time point (P <.05). One patient was discontinued early from latanoprost treatment because of eyelid swelling; also, latanoprost caused more hyperemia than brimonidine (P =.04). CONCLUSION: This study suggests latanoprost dosed daily in the evening statistically reduces intraocular pressure more during daytime and evening hours than brimonidine dosed twice daily. Brimonidine may not consistently decrease the pressure 10 and 12 hours past dosing from nontreated levels.

Adrenergic alpha-Agonists↗

Factors that relate to treatment duration for patients with palatally impacted maxillary canines.

The objectives of this study were to determine the relationship between the initial position of a palatally impacted maxillary canine (as seen on a panoramic radiograph) and the duration of orthodontic treatment and to determine whether a difference in treatment duration existed between patients with bilateral palatally impacted canines and patients with unilateral impaction. A total of 47 adolescent subjects were chosen (9 subjects with unilateral impactions and 18 subjects with bilateral impactions). All subjects had full fixed orthodontic appliances placed. The treatment duration of this group was compared with that of a control group with similar characteristics but without the impacted canine. The results showed that the average duration of treatment was 22.4 months for the control group, 25.8 months for the unilateral-impacted group, and 32.3 months for the bilateral-impacted canine group. The length of treatment for the impacted canine sample was related to the age of the patient at the start of treatment; younger patients required a longer treatment. The younger the patient, the more severely impacted the canine. The bilateral-impacted canine group had at least 1 canine that was more severely impacted than the impacted canine in the unilateral-impacted group. If the canine was impacted less than 14 mm from the occlusal plane, treatment duration averaged 23.8 months; if the canine was impacted more than 14 mm from the occlusal plane, treatment duration averaged 31.1 months.

Adolescent↗

Effect of timolol 0.5% gel and solution on pulmonary function in older glaucoma patients.

PURPOSE: To evaluate the effect of timolol maleate solution or gel forming solution versus placebo on pulmonary function in patients with primary open-angle glaucoma or ocular hypertension without reactive airway disease. METHODS: After a screening visit, each patient was randomized by a Latin square technique to receive placebo twice daily, 0.5% timolol solution twice daily, or 0.5% timolol gel once a day (placebo given as second dose) to each eye for 2 weeks. Subjects then were crossed over to the two other treatments for 2-week treatment intervals. At each visit, patients were received a dose 15 minutes before pulmonary function testing. RESULTS: This study began with 25 patients, and 20 finished the trial. There was no difference between treatment groups for the forced expiratory volume at one second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio (P > 0.1). The mean FEV1 for timolol solution, timolol gel, and placebo was 2.42 L, 2.45 L, and 2.50 L, respectively. The mean FVC for timolol solution, timolol gel, and placebo was 3.33 L, 3.38 L, and 3.44 L, respectively. No difference in intraocular pressure was observed between the timolol solution (17.1 +/- 3.3 mm Hg) and timolol gel (17.1 +/- 3.6 mm Hg) between the treatment periods (P > 0.1). No difference in side effects was observed between treatment groups (P > 0.05). CONCLUSIONS: In older patients with primary open-angle glaucoma or ocular hypertension without reactive airway disease, nonselective beta-blockers should not worsen pulmonary function.

Adrenergic beta-Antagonists↗

Cerebrovascular risk factors and stroke subtypes: differences between ethnic groups.

BACKGROUND AND PURPOSE: The excess risk of stroke seen in the black population has not been explained by differences in age, sex, and social class, although differences in the frequency of cerebrovascular risk factors may be partly responsible. Data on risk factor profiles for the UK black stroke population are sparse. Previous studies have contrasted the association of cerebrovascular risk factors between hemorrhagic and ischemic stroke and between etiologic subtypes of infarct. The relationship of cerebrovascular risk factors to clinical classifications of stroke, however, has been little examined. The aim of this study was to establish the frequency of cerebrovascular risk factors in patients with first-ever strokes in the South London, UK, population and to examine the relationship of these risk factors to both ethnicity and Bamford stroke subtype. METHODS: The study included 1254 first-ever stroke patients registered in the South London Community Stroke Register between 1995 and 1998; 995 patients (79.3%) were white, 203 (16.2%) were black, 52 (4.1%) were of other ethnic origin, and 4 (0. 3%) were of unknown ethnic origin. RESULTS: In multivariate analysis, increasing age (P:<0.001) and previous cerebrovascular disease (P:=0.007) were independently associated with infarct rather than hemorrhage. Atrial fibrillation was associated with all nonlacunar (P:=0.02), total anterior circulation (P:=0.007), and partial anterior circulation infarcts (P:=0.02) compared with the lacunar group. All other risk factors were similar between infarct subtypes. Risk factors for hemorrhage subtypes were similar in multivariate analysis; increasing age was the only factor associated with primary intracerebral hemorrhage over subarachnoid hemorrhage (P:<0.001). The black stroke population suffered significantly less atrial fibrillation (P:=0.001) and engaged in less alcohol excess (P:<0. 001) and were less likely to have ever smoked (P:<0.001). Hypertension (P:<0.001) and diabetes mellitus (P:<0.001) were more prevalent in the black population. CONCLUSIONS: Physiological cerebrovascular risk factors for the UK black population are similar to those of the US black population, but behavioral risk factors differ. Risk factors differ between ethnic groups in the United Kingdom, and future measures for secondary prevention should take this into consideration. Bamford clinical subtypes bear little association with cerebrovascular risk factors. Other classification systems, such as those that classify stroke by etiology, may be more useful in explaining the excess risk of stroke and the scope for its prevention.

Age Distribution↗