Postcataract ptosis. A randomized, double-masked comparison of peribulbar and retrobulbar anesthesia

PURPOSE: A randomized, double-masked study of 317 patients was conducted to determine if the incidence of postcataract ptosis is greater with retrobulbar or two-injection peribulbar injection anesthesia. METHODS: Surgery consisted of a planned extracapsular extraction with posterior chamber lens implantation, and no superior rectus bridle suture was used. Ptosis was quantitatively documented preoperatively and postoperatively at 1, 2, 5, and 90 days by the surgeon, photographically at 90 days by a masked observer, and subjectively by the patients. Postcataract ptosis was defined as a drop in the lid margin of 2 mm or greater after correcting for any change in the fellow eye. RESULTS: The incidence of ptosis at 90 days in patients given peribulbar anesthesia was 5.8% and in patients given retrobulbar anesthesia 5.5%, and this difference was not statistically significant (P = 0.90). Eighteen percent of patients in both groups reported a change in the appearance of their eyelids. There was a moderate, positive correlation among patients who reported a change in their lid position and objective measurements of ptosis. Preoperative clinical measurements of vertical lid fissure width and levator function, and the appearance of the lid crease or superior sulcus were not predictive for the development of postoperative ptosis at 90 days; the best predictor was the presence of ptosis in the immediate postoperative period. CONCLUSION: The incidence of postcataract ptosis is the same whether two injection peribulbar or retrobulbar anesthesia is used.     

Effect of nabumetone on hemostasis during arthroscopic knee surgery

The known effects of commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) on hemostatic parameters have led to concern over their use in the perioperative period. Nabumetone, unlike other NSAIDs, has little effect on collagen-induced platelet aggregation. To evaluate the effect of nabumetone 2000 mg daily on other hemostatic parameters (e.g., bleeding time, prothrombin time, and partial thromboplastin time) in the clinical setting, this double-masked study was conducted in patients with osteoarthritis undergoing arthroscopic knee surgery. After a 1-week placebo washout period, 58 patients were randomized to receive nabumetone and 53 were randomized to receive placebo. They were assessed before surgery (after 1 to 2 weeks of treatment) and again after surgery (after an additional 3 weeks of treatment). The study was designed to have 90% power to show equivalence in bleeding time to within 1.5 minutes, a difference assumed to be of no clinical importance. No meaningful differences were observed between the groups in any of the measured hemostatic parameters. Before surgery, the bleeding time increased by only 0.3 minutes with nabumetone and decreased by 0.2 minutes with placebo. The mean (+/- SD) difference between the groups in change from baseline was 0.5 +/- 0.3 minutes. After surgery, the changes were 0.1 minutes and 0.0 minutes, respectively, and the difference between groups was 0.2 +/- 0.3 minutes. These differences were neither statistically nor clinically significant, and maximum individual increases were similar in each group. Furthermore, there were no reports of abnormal bleeding in the operative knees. The results of this study show that nabumetone had little or no effect on hemostasis and suggest that this drug can be used safely in the perioperative period.     

A double-masked, randomized 1-year study comparing dorzolamide (Trusopt), timolol, and betaxolol. International Dorzolamide Study Group

OBJECTIVE: To investigate the safety profile and efficacy of 2.0% dorzolamide hydrochloride, when administered three times daily for up to 1 year, compared with that of 0.5% timolol maleate and 0.5% betaxolol hydrochloride, each administered twice daily. In addition, the effect of adding dorzolamide to the regimen of patients with inadequate ocular hypotensive efficacy while they were receiving one of the two beta-adrenoceptor antagonists and the effect of adding timolol to the regimen of patients receiving dorzolamide were also evaluated. DESIGN: A double-masked, randomized, parallel comparison. SETTING: Multinational study at 34 international sites. PATIENTS: Five hundred twenty-three patients with open-angle glaucoma or ocular hypertension, 17 to 85 years of age. Patients currently using ocular hypotensive medications were required to undergo a washout. INTERVENTION: Two percent dorzolamide three times a day, 0.5% timolol (Timoptic, Merck, Whitehouse Station, NJ) twice daily, and 0.5% betaxolol solution (Betoptic, Alcon, Fort Worth, Tex) twice daily. RESULTS: At 1 year, the mean percent reduction in intraocular pressure at peak of 2% dorzolamide, 0.5% timolol, and 0.5% betaxolol was approximately 23%, 25%, and 21%, respectively. At afternoon trough, the mean percent reduction in intraocular pressure was 17%, 20%, and 15% for dorzolamide, timolol, and betaxolol, respectively. CONCLUSIONS: The ocular hypotensive efficacy of 2.0% dorzolamide, given three times a day, is comparable with that of 0.5% betaxolol, given twice daily, for up to 1 year. In addition, long-term use of dorzolamide was not associated with clinically meaningful electrolyte disturbances or systemic side effects commonly observed with the use of oral carbonic anhydrase inhibitors.     

A double-masked, randomized, 1-year study comparing the corneal effects of dorzolamide, timolol, and betaxolol. Dorzolamide Corneal Effects Study Group

OBJECTIVE: To compare the long-term effects of dorzolamide hydrochloride (Trusopt, Merck and Co Inc, White-house Station, NJ), timolol maleate, and betaxolol hydrochloride on corneal endothelial cell density and corneal thickness. METHODS: This 1-year multicenter study was conducted in 298 patients with ocular hypertension or open-angle glaucoma who had a baseline central corneal endothelial cell density greater than 1500 cells/mm2 and central corneal thickness less than 0.68 mm in each eye. Patients were randomized to 0.5% betaxolol twice daily, 0.5% timolol twice daily, or 2.0% dorzolamide 3 times daily. Specular microscopy and ultrasonic pachymetry of the central cornea was performed at baseline and 6 and 12 months following institution of therapy. Endothelial cell densities were determined by a single masked observer. RESULTS: The mean percent changes from baseline for both outcome measures were similar in all 3 treatment groups at both 6 and 12 months. After 1 year of treatment, the mean percent loss in endothelial cell density from baseline was 3.6%, 4.5%, and 4.2% for the dorzolamide, timolol, and betaxolol groups, respectively. The mean percent change from baseline for corneal thickness was 0.47%, -0.25%, and 0.39% for the dorzolamide, timolol, and betaxolol groups, respectively. CONCLUSIONS: Dorzolamide is equivalent to timolol and betaxolol in terms of the change in central endothelial cell density and thickness after 1 year of therapy. All 3 treatments exhibit good long-term corneal tolerability in patients with normal corneas at baseline.     

Experimental osteoarthritis in the rabbit knee joint

The development of arthrotic-like changes following the resection of the cruciate ligaments in the knee joint of rabbits has been studied at intervals from 2 weeks to 10 months in 35 animals. Signs of cartilage degeneration were followed by changes in the subchondral bone, where formation of osteophytes and condensation took place. An increased vascular supply was demonstrated by microangiographic and scintigraphic investigations. The uptake of 18F and 99mTc-polyphosphate reached a maximal value about 2 months after the operation and then diminished despite further development of arthrotic changes.     

Estrogen replacement therapy and worsening of radiographic knee osteoarthritis: the Framingham Study

OBJECTIVE: To examine whether estrogen replacement therapy (ERT) prevents worsening of radiographic knee osteoarthritis (OA) in elderly women. METHODS: A total of 551 women ages 63-91 years (mean age 71) in the Framingham Study were followed up from biennial examination 18 (1983-1985) to examination 22 (1992-1993). Data on postmenopausal ERT were obtained every 2 years. Subjects were classified into 3 groups according to their estrogen use at biennial examination 18: never users (n = 349), past users (n = 162), and current users (n = 40). Women received anteroposterior weight-bearing knee radiographs at examinations 18 and 22. Using the Kellgren and Lawrence criteria, global radiographic knee OA was assessed, (grade range 0-4) and individual radiographic features, such as osteophytes and joint space narrowing, were scored from 0 to 3. Worsening was defined as either development of radiographic OA that was not present at baseline (incident OA) or progression of baseline radiographic OA by > or =1 Kellgren and Lawrence grade (progressive OA). Potential confounding factors included age, body mass index, weight change, smoking, knee injury, physical activity level, and bone mineral density at the femoral neck. RESULTS: During 8 years of followup, 17.4% of knee radiographic scores worsened by 1 grade and 5.8% by 2 or 3 grades among never users of ERT. Among current estrogen users, only 11.7% of knee radiographic scores worsened by 1 grade and none worsened by more than 1 grade. After adjusting for age and other potential confounding factors, the relative risk of incident radiographic knee OA in comparison with never users of estrogen was 0.8 (95% confidence interval [95% CI] 0.5-1.4) in past users and 0.4 (95% CI 0.1-3.0) in current users. Current use of estrogen also showed a trend toward decreased risk of progressive knee OA compared with never use (odds ratio [OR] 0.5, 95% CI 0.1-2.9). When both incident and progressive radiographic knee OA cases were combined, current ERT use had a 60% decreased risk compared with never use (OR 0.4, 95% CI 0.1-1.5). CONCLUSION: This is the first prospective cohort study to examine the effects of ERT on radiographic knee OA. The results indicate that current use of ERT had a moderate, but not statistically significant, protective effect against worsening of radiographic knee OA among elderly white women. These findings corroborate those of cross-sectional studies and point further to a potential benefit of female hormones in OA.     

Is knee joint proprioception worse in the arthritic knee versus the unaffected knee in unilateral knee osteoarthritis?

OBJECTIVE: Neuromuscular joint protection requires proprioceptive input and motor output. Impairment of proprioception in knee osteoarthritis (OA) may contribute to, and/or result from, the disease. If this impairment was exclusively a local result of OA, a between-knee difference would be expected in patients with unilateral OA (UOA). To explore causal directions, 2 hypotheses were tested: 1) proprioception is worse in UOA patients versus elderly controls; 2) proprioception is worse in the arthritic knee versus the unaffected knee in UOA patients. METHODS: Twenty-eight UOA patients (Kellgren-Lawrence grade > or =2 in 1 knee and <2 in the other knee) and 29 elderly controls were enrolled. The unaffected knee of each UOA patient and both knees of the elderly controls were required to meet symptom, examination, and radiographic criteria. Proprioception (detection threshold of joint displacement after slow, passive, automated knee motion), body mass index, pain, functional status, range of motion, and laxity were measured. RESULTS: UOA patients had worse proprioception than did elderly controls, in either knee. A between-knee difference was not found in UOA patients. CONCLUSION: Impaired proprioception is not exclusively a local result of disease in knee OA. The relative importance of impaired proprioception in the development and progression of knee OA will require longitudinal study.     

Epidemiology and features of knee osteoarthritis in the Ivory Coast

We retrospectively studied 369 cases of knee osteoarthritis in 240 patients seen at the Cocody Teaching Hospital in Abidjan, Ivory Coast, from November 1984 through March 1989. There were 126 cases (34.14%) of patellofemoral osteoarthritis, 104 cases (28.18%) of femorotibial osteoarthritis and 139 cases (37.66%) of global knee osteoarthritis (defined as patellofemoral and femorotibial osteoarthritis in the same joint). There was a marked female bias (80.42% of patients). Onset was earlier in patellofemoral osteoarthritis (51.25 years) than in femorotibial osteoarthritis (57.85 years). Half the patients (51.25%) were housewives. The Akan and Mandé ethnic groups contributed 61.54% and 33.03% of patients, respectively. Obesity was present in 19.04% of cases of patellofemoral osteoarthritis and in 10.57% of cases of femorotibial osteoarthritis. Of the patients with femorotibial osteoarthritis, 20.20% had a history of arthritis of the knee and of those with global knee osteoarthritis, 12.23% reported a prior injury to the knee. Varus deformity was found in 24.03% and valgus deformity in 19.23% of the patients with femorotibial osteoarthritis.     

Risk factors for incident radiographic knee osteoarthritis in the elderly: the Framingham Study

OBJECTIVE: Knee osteoarthritis (OA) is highly prevalent, especially in the elderly. Preventive strategies require a knowledge of risk factors that precede disease onset. The present study was conducted to determine the longitudinal risk factors for knee OA in an elderly population. METHODS: A longitudinal study of knee OA involving members of the Framingham Study cohort was performed. Weight-bearing knee radiographs were obtained in 1983-1985 (baseline) and again in 1992-1993. Incident disease was defined as the occurrence of new radiographic OA (Kellgren and Lawrence grade > or = 2 on a 0-4 scale) in those without radiographic OA at baseline. Risk factors assessed at baseline and in the interim were tested in univariate and multivariate equations to evaluate their association with incident knee OA. RESULTS: Of 598 patients without knee OA at baseline (mean age 70.5 years, 63.7% women), 93 (15.6%) developed OA. After adjustment for multiple risk factors, women had a higher risk of OA than did men (adjusted odds ratio [OR] = 1.8, 95% confidence interval [95% CI] 1.1-3.1). Higher baseline body mass index increased the risk of OA (OR = 1.6 per 5-unit increase, 95% CI 1.2-2.2), and weight change was directly correlated with the risk of OA (OR = 1.4 per 10-lb change in weight, 95% CI 1.1-1.8). Physical activity increased the risk of OA (for those in the highest quartile, OR = 3.3, 95% CI 1.4-7.5). Smokers had a lower risk than did nonsmokers (for those who smoked an average of > or = 10 cigarettes/day, OR = 0.4, 95% CI 0.2-0.8). Factors not associated with the risk of OA included chondrocalcinosis and a history of hand OA. Weight-related factors affected the risk of OA only in women. CONCLUSION: Elderly persons at high risk of developing radiographic knee OA included obese persons, nonsmokers, and those who were physically active. The direction of weight change correlated directly with the risk of developing OA.     

Incidence and risk factors for radiographic knee osteoarthritis in middle-aged women: the Chingford Study

In susceptible mouse strains, the wild-type Daniel's (wt-DA) strain of Theiler's murine encephalomyelitis virus induces a persistent central nervous system (CNS) infection with chronic demyelination. The virus is cleared from resistant mice with no resulting demyelination. We characterized the role of the DA L* protein in late demyelination and persistent infection. The DA genome has two alternative reading frames, encoding the virus polyprotein and L*, respectively. The mutant virus DAL*-1 fails to synthesize L* and does not persist in the CNS of wt-DA-susceptible SJL/J or B10.S mice. Since class I-restricted cytotoxicity has been shown to determine resistance to virus persistence and demyelination in this model, virus-specific cytotoxicity in the CNS of DA-resistant (B6 or B10) and -susceptible (SJL/J and B10.S) mice during the acute stage of DA and DAL*-1 infection was characterized. Following intracerebral inoculation with DAL*-1, virus-specific Db- and Kb-restricted CTLs were demonstrated in the CNS of resistant B10 mice, whereas only Db-restricted CTL were found in wt-DA-inoculated mice. CTLs specific to wt-DA or DAL*-1 recognized class I-presented peptides from either of the viruses. Of particular interest, Ks-restricted virus-specific cytotoxicity-restricted CTLs were identified in the CNS of susceptible SJL/J (H-2s) and B10.S (H-2s) mice inoculated with DAL*-1. In contrast, no virus-specific CTLs were identified in the CNS of SJL/J and B10.S mice inoculated with wt-DA. We propose that L* inhibits the generation of H-2K-restricted virus-specific cytotoxicity in the CNS, permitting a persistent infection in susceptible strains, with subsequent inflammatory demyelination in the CNS similar to that in human multiple sclerosis.     

Generation II knee bracing for severe medial compartment osteoarthritis of the knee

OBJECTIVE: The tolerability of clonazepam in geropsychiatric inpatients was examined in patients with and without a diagnosis of dementia. DESIGN: Forward-looking retrospective study comprising consecutive patients placed on clonazepam. SETTING: A geropsychiatry unit of a large Veterans Affairs Medical Center. PATIENTS: All geropsychiatry inpatients placed on clonazepam over a 21-month period of time. MEASURE: Mini-Mental State Examination, Brief Psychiatric Rating Scale, Cohen-Mansfield Agitation Inventory and the Rating Scale for Side Effects were performed at admission and discharge as part of an ongoing database. RESULTS: Twenty-four geropsychiatric inpatients were treated with clonazepam (mean dose of 1.2 mg for a minimum of 2 weeks) during the 21 months studies. About one half of the patients had a primary diagnosis of dementia and the remainder had a diagnosis of an affective or psychotic disorder. Two of these patients were discontinued because they had responded to the acute need for clonazepam and a third patient was discontinued because of the development of sedation and confusion. For the remaining 21 patients, scores improved significantly on the Brief Psychiatric Rating Scale (p = 0.017), the Cohen-Mansfield Agitation Inventory (p = 0.011), the Rating Scale for Side Effects (0.004) and the Global Assessment of Functioning (p < 0.000), with no differences in amount of improvement between demented and non-demented patient groups. Scores on the Mini-Mental State Examination remained unchanged. CONCLUSIONS: Clonazepam shows promise as a benzodiazepine with good tolerability in the elderly.     

Reliability of gait measurements in people with osteoarthritis of the knee

BACKGROUND AND PURPOSE: The purpose of this study was to assess the intrasession and intersession reliability of measurements of quantitative gait variables at two self-selected walking speeds. SUBJECTS: Forty-one patients with osteoarthritis in one or both knees who were referred for physical therapy participated. METHODS: Three measurements were made at 1-week intervals. The quantitative gait variables of walking speed, cadence, and stride length were measured using an 8-m electronic footswitch walkway. At each measurement, subjects were asked to walk five times at a self-selected pace that they considered to be normal and five times at a self-selected pace that they considered to be fast. RESULTS: At the normal walking speed, although intraclass correlations were consistently high for all gait variables, an additive factor within and across the first two measurements was evident even when a mean of several trials was used. At the fast walking speed, the intraclass correlations were again consistently high for all gait variables, but there were no changes within or across the measurements. CONCLUSION AND DISCUSSION: The data suggest that quantitative gait analysis is a practical objective assessment tool for persons with osteoarthritis of the knee. Gait at the fast walking speed, however, will provide the more reliable stable measure on which to evaluate the effect of therapy when compared with gait at the normal walking speed. The comparative responsiveness to change between the two walking speeds still needs to be determined.     

Characterization of the transient intermediates generated from the photoexcitation of nabumetone: a comparison with naproxen

The photochemical and photophysical properties of nabumetone (4-[6-methoxy-2-naphthyl]-2-butanone) were examined employing conventional and time-resolved spectroscopic techniques. The naphthalene-like nabumetone triplet is formed with 29% efficiency in acetonitrile. Singlet oxygen formation was also detected in this solvent with a phi delta value of 0.19. A naphthalene-like radical cation absorption, formed via biphotonic processes, was also detected. The reactivity of both the triplet and radical cation of nabumetone toward different substrates was examined. The photochemical properties of nabumetone are compared with those of naproxen, a structurally related acidic nonsteroidal anti-inflammatory drug. For these two anti-inflammatory agents, a type II photosensitization process is most likely responsible for their phototoxicity.     

Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients. International MELISSA Study Group. Meloxicam Large-scale International Study Safety Assessment

Although widely used, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with a high incidence of gastrointestinal (GI) side-effects. Inhibition of the cyclooxygenase (COX) enzyme is the basis for both the efficacy and toxicity of NSAIDs. The discovery of two COX isoforms, constitutive COX-1 and inducible COX-2, has led to the hypothesis that selective inhibition of COX-2 will minimize the potential for GI toxicity without compromising efficacy. The Meloxicam Large-scale International Study Safety Assessment (MELISSA) trial reported here was therefore set up to investigate the tolerability of meloxicam, a preferential inhibitor of COX-2, compared to diclofenac. MELISSA was a large-scale, double-blind, randomized, international, prospective trial, conducted over 28 days in patients with symptomatic osteoarthritis. Patients received either meloxicam 7.5 mg or diclofenac 100 mg slow release, the recommended doses for the treatment of osteoarthritis. Evaluation of the profile of adverse events was the main aim of the trial, together with assessment of efficacy. A total of 9323 patients received treatment (4635 and 4688 in the meloxicam and diclofenac groups, respectively). Significantly fewer adverse events were reported by patients receiving meloxicam. This was attributable to fewer GI adverse events (13%) compared to diclofenac (19%; P < 0.001). Of the most common GI adverse events, there was significantly less dyspepsia (P < 0.001), nausea and vomiting (P < 0.05), abdominal pain (P < 0.001) and diarrhoea (P < 0.001) with meloxicam compared to diclofenac. Five patients on meloxicam experienced a perforation, ulcer or bleed vs seven on diclofenac (not significant). No endoscopically verified ulcer complication was detected in the meloxicam group compared to four with diclofenac. There were five patient days of hospitalization in patients on meloxicam compared to 121 with diclofenac. Adverse events caused withdrawal from the study in 254 patients receiving meloxicam (5.48%) compared to 373 (7.96%) on diclofenac (P < 0.001). These differences were attributable to differences in reported GI adverse events (3.02% on meloxicam vs 6.14% on diclofenac; P < 0.001). Differences in efficacy, as assessed by visual analogue scales, consistently favoured diclofenac. In all instances, 95% confidence intervals did not cross zero, suggesting a statistically significant effect. However, differences were small (4.5-9.01% difference) and did not reach pre-determined levels of clinical significance. Nevertheless, significantly more patients discontinued meloxicam because of lack of efficacy (80 out of 4635 vs 49 out of 4688; P < 0.01). The MELISSA trial confirms earlier studies suggesting that meloxicam has a significantly improved GI tolerability profile in comparison with other NSAIDs, including diclofenac. These results may in part reflect the preferential COX-2 selectivity of meloxicam, although the dose and other aspects of tolerability may be important. These results may provide support for the hypothesis that selective inhibition of COX-2 relative to COX-1 might be an effective approach towards improved NSAID therapy.     

Quadriceps weakness in knee osteoarthritis: the effect on pain and disability

OBJECTIVES: (1) To determine the importance of quadriceps strength, structural change, and psychological status in terms of knee pain in the community. (2) To determine the relative importance of quadriceps function, structural change, and psychological status with respect to disability in subjects with knee pain. METHODS: 300 men and women with pain and 300 controls without pain (aged 40-79) were seen. Isometric quadriceps strength (MVC) was measured and muscle activation was assessed by twitch superimposition. Disability (Western Ontario McMaster Osteoarthritis Index (WOMAC)) and anxiety and depression were assessed (Hospital Anxiety and Depression Index (HAD)). Radiographs were obtained of the tibiofemoral and patellofemoral joints and total score for osteophyte, narrowing, and sclerosis calculated for each knee. RESULTS: Subjects with knee pain had lower voluntary quadriceps strength than those without pain (p < 0.005). Quadriceps activation was also lower (p < 0.005), but did not fully explain the reduction in strength. When analysed by multiple logistic regression: quadriceps strength (odds ratio 18.8, CI 4.8, 74.1 for MVC < or = 10 kgF); depression (odds ratio 2.4, CI 1.0, 5.5 for HAD score > or = 8); and radiographic change (odds ratio 4.1, CI 1.9, 8.6 for radiographic score > or = 4) were independently associated with pain. In those with knee pain, disability was independently associated with quadriceps strength (odds ratio 8.2, CI 1.5, 44.4 for MVC < or = 10 kgF) and depression (odds ratio 6.2, CI 2.1, 18.0 for HAD score > or = 8); but not with radiographic score. CONCLUSIONS: Quadriceps strength is strongly associated with knee pain and disability in the community, even when activation and psychological factors are taken into account. This has important therapeutic implications.     

The relation between osteoporosis of the spine and osteoarthritis of the knee. A study using dual energy X-ray absorptiometry and radiographs

We investigated the relation between osteoporosis of the spine and osteoarthritis of the knee using dual energy X-ray absorptiometry of the lumbar spine to measure bone mineral density and radiographs of the knee in 82 randomly selected females (mean age 77.5 years). Radiographs of the knee were divided into a normal and severe group. The bone mineral density of the severe group was significantly more than that of the normal group.