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BACKGROUND: Frailty reflects a state of increased risk of negative health outcomes, such as falls and mortality. Self-management in recognition and monitoring of frailty is a prerequisite for effective and efficient care for the elderly. Mobility may be self-monitored with simple reliable tests, such as maximum step length (MSL) test, gait speed (GS) test, or chair rise test (CR). AIM: The aim was to investigate whether a complex frailty assessment may be replaced by simple stand alone mobility tests as a prerequisite for self-monitoring of frailty. DESIGN: This was an observational cross-sectional study. SETTING: The study was performed in an outpatient clinic. POPULATION: The study subjects were community-dwelling older people aged 70 years or older. METHODS: In all subjects, frailty status was assessed using a standardised geriatric assessment that included Fried's frailty phenotype and the Frailty Index (FI). Mobility was assessed with the MSL, GS and CR. RESULTS: A total of 593 subjects with mean age of 76.8 years (±4.8 [SD]), 56% female, participated in the study. GS showed a correlation of r=-0.60 with both the Fried score and the FI. The MSL correlated best with the Fried score: r=-0.52, and the CR correlated best with the FI: r=0.51. The GS had an area under the curve of 0.92 for assessing the dichotomised frailty state. CONCLUSION: Compared with step length and chair rise time, gait speed has the strongest correlation with frailty, the highest diagnostic value, and it is the simplest single measure that can replace the complex frailty assessment as a self-test for monitoring frailty at home. CLINICAL REHABILITATION IMPACT: THE self-monitoring of frailty is likely to be possible with GS, which may be a valuable tool for empowering older individuals.

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The walking energy cost test (WECT) is a useful tool when measuring ambulatory function in children with motor disorders. However, data on the reliability of this test in Duchenne muscular dystrophy (DMD) is not available. In this study we established the reliability of the WECT and the commonly used six-minute walk test (6MWT) in 19 boys with DMD, aged 6-12years. Participants performed the WECT and 6MWT twice within three weeks. Reliability was determined for walking distance (D, m) and gross energy cost (EC, Jkg(-1)m(-1)), using the intraclass correlation coefficient (ICC2,1) and smallest detectable change (SDC). Reliability for walking distance was good, with an ICC of 0.92 [95% CI: 0.81-0.97] and 0.83 [CI: 0.53-0.94] for the 6MWT and WECT, respectively, and an ICC of 0.85 [CI: 0.64-0.94] for gross EC. SDCs were 12.2% for D6MWT, 12.7% for DWECT and 18.5% for gross EC. In conclusion, in young boys with DMD, the reliability of both the WECT and 6MWT for assessing walking distance is adequate. Gross EC, as assessed with the WECT is also reliable and sufficiently sensitive to detect change in walking strain following interventions at group level.

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BACKGROUND: A decline in mobility is a common feature of multiple sclerosis (MS). Community walking scales are used to categorize patients in their ability to move independently. The first purpose of this study was to determine which specific gait speed corresponded with the categories of the Modified Functional Walking Categories (MFWC). The second purpose was to determine the Minimally Important Change (MIC) in absolute gait speed using the MFWC and Expanded Disability Status Scale (EDSS) as external criteria. METHOD: MS patients were measured six times in 6 years. Gait velocity was measured with the 10-metre timed walk test (10-m TWT), the severity of MS was determined with the EDSS, and community walking was assessed with the MFWC. For each category of the MFWC, Receiver Operating Characteristic (ROC) curves were used to find the best possible cut-off point on the 10-m TWT. The MIC in absolute gait speed was determined using a change of one category on the MFWC or one point on the EDSS. RESULTS: A strong relationship was found between gait speed and the MFWC; all areas under the ROC curves (AUCs) were between 0.74 and 0.86. The MIC in absolute gait speed could not be determined, because the AUCs were below the threshold of 0.70 and changes in gait speed were small. CONCLUSIONS: Gait speed is related to community walking, but an MIC in absolute gait speed could not be determined using a minimally important change on the MFWC or the EDSS as external criteria.

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AIM: To evaluate the incidence of and risk factors for ocular complications in multibacillary (MB) leprosy patients following completion of 2 year, fixed duration, multidrug therapy (MDT). METHODS: Biannual eye examinations were conducted prospectively on a cohort of MB patients who had completed MDT and followed up for 5 years. The incidence of ocular pathology was calculated as the number of events per person year of event free follow up of patients who did not have the specific finding before completion of MDT. RESULTS: 278 patients had one or more follow up visits after completion of MDT. The incidence of lagophthalmos was 0.24%/patient year (95% CI 0.10% to 0.37%); corneal opacity, 5.35%/patient year (95% CI 4.27% to 6.70%); uveal involvement, 3.78%/patient year (95% CI 2.96% to 4.83%); and cataract that reduced vision to 6/18 or less, 2.4%/patient year (95% CI 1.77% to 3.26%). Overall, 5.65%/patient year (95% CI 4.51% to 7.09%) developed leprosy related ocular disease and 3.86%/patient year (95% CI 3.00% to 4.95%) developed leprosy related, potentially blinding ocular pathology during the period following MDT. Age and other disability also predicted incident eye disease. CONCLUSIONS: Every year, approximately 5.6% of patients with MB who have completed MDT can be expected to develop new ocular complications of leprosy, which often (3.9%) are potentially vision threatening. Because many of these complications cannot be detected without slit lamp examination, periodic monitoring, particularly of older patients and those with other disability, is recommended, in order to detect and treat ocular complications satisfactorily.

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AIM: To evaluate the incidence of and risk factors for ocular complications in multibacillary (MB) leprosy patients during their 2 year, fixed duration, multidrug therapy (MDT). METHODS: Periodic eye examinations were conducted prospectively on a cohort of 301 consecutive newly diagnosed MB patients every 6 months during their 2 year course of MDT. Incidence of ocular pathology was calculated as the number of events per person year of event free follow up of patients who did not have the specific finding at baseline. RESULTS: 292 (97%) patients had one or more follow up visits. The incidence of lagophthalmos was 1.2%/patient year (95% CI 0.5% to 2.8%); corneal opacity was 7.4%/patient year (95% CI 5.1% to 10.6%); uveal involvement was 5.1%/patient year (95% CI 3.3% to 7.8%), and cataract that reduced vision to 6/18 or less was seen in 4.3%/patient year (95% CI 2.7% to 6.9%) of patients. Overall, 23 individuals (5.8%/patient year, 95% CI 3.9 to 8.8) developed leprosy related potentially blinding pathology during the 2 years of MDT. CONCLUSIONS: Approximately 20% of patients with MB leprosy can be expected to develop ocular complications of leprosy during a 2 year course of MDT, many (11%) of which are potentially vision threatening. Ophthalmological monitoring to detect and treat ocular complications at defined intervals during MDT is indicated.

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Galactokinase deficiency (McKusick 230200) is a rare autosomal recessive inborn error of galactose metabolism. Cataract and, rarely, pseudotumor cerebri caused by galactitol accumulation seem to be the only consistently reported abnormalities in this disorder. We performed a literature search to obtain information on the clinical spectrum of galactokinase deficiency. A total of 25 publications were traced describing 55 galactokinase-deficient patients. Cataract was reported in most patients. Clinical abnormalities other than cataract were reported in 15 (35%) out of 43 cases on which information was available. However, all symptoms were reported infrequently and a causal relationship with the galactokinase deficiency is unlikely. As cataract and pseudotumor cerebri appear to be the sole complications of galactokinase deficiency, the outcome for patients with galactokinase deficiency is much better than for patients with classical galactosaemia (McKusick 230400), a more common autosomal recessive disorder of galactose metabolism caused by galactose-1-phosphate uridyltransferase (GALT; EC 2.7.7.12) deficiency. Long-term follow-up of patients with this disorder has shown that, in spite of a severely galactose-restricted diet, most patients develop abnormalities such as a disturbed mental and/or motor development, dyspraxia and hypergonadotropic hypogonadism. Endogenous production of galactose has been considered an important aetiological factor. Although damage may well occur in utero, available evidence suggests that damage will continue after birth. Inhibition of galactokinase may then be a promising approach for controlling damage in GALT-deficient patients.

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OBJECTIVE: To synthesize the findings of the randomized trials of regional anesthesia management strategies for cataract surgery. DESIGN: Literature review and analysis. METHOD: The authors performed a systematic search of the literature to identify all articles pertaining to regional anesthesia during cataract surgery on adults. One investigator abstracted the content of each article onto a custom-designed form. A second investigator corroborated the findings. The evidence supporting the anesthesia approaches was graded by consensus as good, fair, poor, or insufficient. MAIN OUTCOME MEASURES: Evidence supporting the effectiveness of different forms of regional anesthesia. RESULTS: There was good evidence that retrobulbar and peribulbar blocks provide equivalent akinesia and pain control during cataract surgery. Additionally, sub-Tenon's blocks were at least as effective as retrobulbar and peribulbar blocks. There was good evidence that retrobulbar block provides better pain control during surgery than topical anesthesia, and there was fair evidence that peribulbar block provides better pain control than topical anesthesia. CONCLUSIONS: This synthesis of the literature demonstrates that currently used approaches to anesthesia management provide adequate pain control for successful cataract surgery, but there is some variation in the effectiveness of the most commonly used techniques. Data are needed on patient preferences to determine the optimal strategies for anesthesia management during cataract surgery.

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OBJECTIVE: To assess the methodologic quality of published randomized trials of regional anesthesia management strategies for cataract surgery. DESIGN: Literature review and analysis. METHOD: We performed a systematic search of the literature to identify all articles pertaining to regional anesthesia for cataract surgery on adults. Overall quality scores and scores for individual methodologic domains were based on the evaluations of two investigators experienced in methodologic research who independently reviewed all relevant articles using a quality abstraction form. MAIN OUTCOME MEASURES: Study quality in each of five domains: representativeness, bias and confounding, intervention description, outcomes and follow-up, and statistical quality and interpretation. RESULTS: Eighty-two randomized clinical trials were identified with a mean overall quality score of 44%. The mean domain scores ranged from 37% for representativeness to 58% for outcomes and follow-up. Forty percent or fewer studies received the maximum score for reporting the setting, the population, and the start and end dates; describing the inclusion and exclusion criteria; adequately randomizing subjects; and adequately masking individuals participating in the study. Key outcomes were often inadequately reported, including the distribution of patient-reported pain scores and the mean surgical time. CONCLUSIONS: Greater attention to methodologic quality and detailed reporting of study results will improve the ability of readers to interpret the results of clinical trials assessing regional anesthesia for cataract surgery.

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OBJECTIVES: To compare the incidence of retinal detachment in patients treated with the ganciclovir implant compared with those treated using systemic therapy only, among 511 patients with the acquired immunodeficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis and to describe the influence of highly active antiretroviral therapy (HAART) on retinal detachment incidence. PATIENTS AND METHODS: All patients with AIDS and CMV retinitis at 1 center were followed up prospectively from CMV retinitis diagnosis for incidence of retinal detachment. Patient- and eye-specific data regarding demographic and clinical characteristics were collected at the time of CMV retinitis diagnosis. Use of anti-CMV and antiretroviral treatments and the development of an immunologic response to HAART during follow-up were recorded. RESULTS: No significant difference in the rate of retinal detachment was found between eyes treated with systemic therapy only and those treated with ganciclovir implants, whether used as primary therapy or subsequent to using systemic anti-CMV therapy. The use of HAART was associated with a 60% reduction in retinal detachment rate (P<.001), with the greatest benefit observed among patients who developed an immunologic response to HAART. CONCLUSIONS: Our results suggest that there is no substantial excess risk of retinal detachment when patients with AIDS and CMV retinitis are treated with ganciclovir implants as opposed to systemic anti-CMV therapy only. However, the use of HAART in these patients appears to reduce the risk of retinal detachment substantially.

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Cytomegalovirus (CMV) disease, an opportunistic complication in patients with AIDS, causes substantial morbidity and has high treatment costs. Although prevention of this disease is highly desirable, incremental cost-effectiveness estimates for proposed prophylactic strategies in the era prior to the availability of highly active antiretroviral therapy (HAART) were unfavourable relative to other specific antimicrobial prophylactic strategies in patients with AIDS. With the availability of HAART, several inputs upon which previous estimates of the incremental cost-effectiveness ratio for anti-CMV prophylaxis were based probably changed substantially. To assess the incremental cost effectiveness of prophylaxis in the HAART era, data are needed on visual outcomes and utility for patients with CMV retinitis and AIDS, on better strategies for identifying subpopulations at high risk for CMV disease and on the prophylactic efficacy of valganciclovir. Cost-effectiveness analysis could potentially contribute by exploring thresholds of population risk, prophylactic effectiveness, and drug pricing in order to identify conditions under which prophylaxis for CMV disease in patients with AIDS could potentially become cost effective.

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PURPOSE: To estimate the incidence and describe the characteristics of immune recovery uveitis in patients with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus retinitis treated with highly active antiretroviral therapy. METHODS: The records of all patients with AIDS and cytomegalovirus retinitis from 1995 to 1998 seen at the AIDS Ophthalmology Service of the Johns Hopkins Medical Institutions were reviewed. Eighty-two patients with cytomegalovirus retinitis treated with highly active antiretroviral therapy were identified. Thirty-three patients (40.2%) were classified as responders to highly active antiretroviral therapy, defined as an increase in CD4+ T-cell count by 50 cells/microL or more to a level of 100 cells/microL or more. RESULTS: Immune recovery uveitis occurred in six patients. Among the 33 patients with an immunologic response to highly active antiretroviral therapy, the incidence rate of immune recovery uveitis was 0.109/person-year. Ocular complications associated with immune recovery uveitis included cystoid macular edema (four patients), epiretinal membranes (two patients), and optic disk neovascularization (one patient). CONCLUSIONS: Immune recovery uveitis was uncommon in our population but may have vision-impairing complications.

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Three vision-dependent neuropsychological tests of visual processing--Benton's Facial Recognition (FR), Judgment of Line Orientation (JLO), and Visual Form Discrimination (VFD)--were administered to subjects on the same day as routine ophthalmic examination. Seventeen subjects had Jaeger near vision of J5 (analogous to 20/50) or worse resulting from refractive error, while 13 control subjects had normal near vision of J1. Neuropsychological test scores of these groups were compared with each other and also the published standardization group for each test. Low near-vision subjects' performances on FR and VFD were significantly poorer than both control group subjects and standardization group subjects, but performance on JLO was not significantly altered. These results demonstrate that visual impairment can result in unexpectedly low scores on certain tests of visual processing, which suggests that poor vision might also affect results of other neuropsychological tests that involve vision, such as tests of visual processing and tests which use vision as a vehicle to deliver test stimuli to the relevant portions of the cortex. We therefore strongly urge examiners to secure control over potential bias resulting from reduced vision by instituting routine near visual acuity testing of all subjects prior to or during neuropsychological assessment.

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Periportal and perivenous hepatocytes were isolated from rat liver by digitonin/collagenase perfusion for investigating the acinar distribution of bile acid synthesis. The specific activity of cholesterol 7 alpha-hydroxylase (EC 1.14.13.17) was 7.9-fold higher in perivenous cells than in periportal hepatocytes. Mass production of bile acids differed 4.4-fold between cultured perivenous and periportal hepatocytes. In contrast, the levels of free cholesterol in homogenates and microsomes derived from both subfractions were similar. Feeding of rats with the bile-acid-sequestering anion-exchange resin colestid resulted in a pronounced stimulation of cholesterol 7 alpha-hydroxylase activity and bile acid mass production, but decreased the perivenous/periportal ratio of both parameters. These results demonstrate that bile acid mass production, but decreased the perivenous hepatocytes, possibly owing to feedback suppression by bile acids from the enterohepatic circulation. Furthermore, the opposite acinar localization of cholesterol and bile acid biosynthesis provides an interesting alternative to current views of the regulation of their metabolic pathways.

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1. The effects of secretin and pancreozymin-C-octapeptide and phosphodiesterase inhibitors on the concentration of adenosine 3',5'-cyclic monophosphate (cyclic AMP) and on the release of enzymes from rat pancreas have been studied. 2. In determininging cyclic AMP by means of the saturation assay of Brown et al. ((1971) Biochem. J. 121, 561-563) it is found essential to purify the pancreatic tissue extract by ion-exchange chromatography prior to the assay. 3. Injection of synthetic secretin or pancreozymin-C-octapeptide in anaesthetized rats in a secretory active dose (0.1 nmol) has no effect on the pancreatic cyclic AMP level. 4. Incubation for up to 10 min of pancreatic slices in Krebs-Ringer bicarbonate glucose medium containing 10(-2) M theophylline as phosphodiesterase inhibitor does not result in an increase of the cyclic AMP level. With 10(-2) M 1-methyl-3-isobutylxanthine as phosphodiesterase inhibitor the level is more than doubled after the first min of incubation and remains constant thereafter. 5. Addition of 3-10(-7) M secretin to slices incubated in the presence of 10(-2) M theophylline causes 84% increase of the cyclic AMP level above control, whereas the addition of 3-10(-7) M pancreozymin-C-octapeptide has no significant effect. In the presence of 10(-2) M 1-methyl-3-isobutylxanthine the latter hormone causes significant increases of up to 34% above control during 10 min of incubation. Secretin in this condition augments the cyclic AMP level by up to 296% above control during a 10 min incubation period. Addition of secretin and pancreozymin-C-octapeptide together has no greater effect than of secretin alone. 6. A broken cell fraction of rat pancreas contains adenylate cyclase activity which can be stimulated to 457 and 600% above the basal activity by 3-10(-7) M pancreozymin-C-octapeptide and secretin, respectively. Incubation of pancreatic slices with either hormone has no effect on the cyclic AMP phosphodiesterase activity in the homogenate of these slices. 7. Pancreozymin-C-octapeptide, dibutyryl cyclic AMP, 1-methyl-3-isobutylxanthine and carbamylcholine cause an elevated release of chymotrypsin from pancreatic slices incubated for 2 h in Krebs-Ringer bicarbonate medium, containing 10 mM glucose, while secretin, cyclic AMP and butyric acid have no significant effect. The release of the cytoplasmic enzyme lactate dehydrogenase is also elevated by dibutyryl cyclic AMP, 1-methyl-3-isobutylxanthine and carbamylcholine, but not significantly by pancreozymin-C-octapeptide. 8. The results support the role of cyclic AMP in the action of secretin, and do not exclude a mediating function of this nucleotide in the actions of pancreozymin in rat pancreas.

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