Standard Diffusion-weighted MRI for the Diagnosis of Central Retinal Artery Occlusion : A Case-Control Study.

PURPOSE: To evaluate diffusion abnormalities of the retina and optic nerve in patients with central retinal artery occlusion (CRAO) using standard stroke diffusion-weighted magnetic resonance imaging (DWI). METHODS: In this case-control study, DWI scans of patients with nonarteritic CRAO were retrospectively assessed for acute ischemia of the retina and optic nerve. Two neuroradiologists, blinded for patient diagnosis, randomly evaluated DWI of CRAO patients and controls (a collective of stroke and transient ischemic attack [TIA] patients) for restrictions of the retina and optic nerve. We calculated statistical quality criteria and analyzed inter-rater reliability using unweighted Kappa statistics. RESULTS: 20 CRAO patients (60,6 ± 17 years) and 20 controls (60,7 ± 17 years) were included in the study. Sensitivity, specificity, positive and negative predictive values for retinal DWI restrictions were 75%/80%/79%/76% (reader 1) and 75%/100%/100%/80% (reader 2), respectively. Unweighted Kappa was κ = 0,70 (95% CI 0,48­0,92), indicating "substantial" interrater reliability. In comparison, sensitivity, specificity, PPV and NPV (positive and negative predictive values) for restrictions of the optic nerve in CRAO were 55%/70%/65%/61% (reader 1) and 25%/100%/100%/57% (reader 2). Inter-rater reliability was "fair" with unweighted Kappa κ = 0,32 (95% CI 0,09­0,56). CONCLUSIONS: Retinal diffusion restrictions were present in a majority of CRAO patients and detectable with reasonable sensitivity, high specificity and substantial inter-rater reliability. Further studies are necessary to study time dependency of retinal diffusion restrictions, improve image quality and investigate the reliability of retinal DWI to discern CRAO from other causes of acute loss of vision.

Time Course and Clinical Correlates of Retinal Diffusion Restrictions in Acute Central Retinal Artery Occlusion.

BACKGROUND AND PURPOSE: Retinal diffusion restrictions were recently identified as a regular finding in acute central retinal artery occlusion. We sought to investigate the influence of technical MR imaging and clinical parameters on the detection rate of retinal diffusion restrictions on standard brain DWI. MATERIALS AND METHODS: In this retrospective cohort study, MR imaging scans of patients with central retinal artery occlusion were assessed by 2 readers for retinal diffusion restrictions on DWI performed within 2 weeks after vision loss. The influence of clinical and technical MR imaging parameters and the time interval between symptom onset and DWI on the presence of retinal diffusion restrictions were evaluated. RESULTS: One hundred twenty-seven patients (mean age, 69.6 [SD 13.9] years; 59 women) and 131 DWI scans were included. Overall, the MR imaging sensitivity of retinal diffusion restrictions in acute central retinal artery occlusion was 62.6%-67.2%. Interrater and intrarater agreement for retinal diffusion restrictions was "substantial" with κinter = 0.70 (95% CI, 0.57-0.83) and κintra = 0.75 (95% CI, 0.63-0.88). Detection of retinal diffusion restrictions did not differ with differences in field strengths (1.5 versus 3T, P = .35) or sequence type (P = .22). Retinal diffusion restrictions were consistently identified within the first week with a peak sensitivity of 79% in DWI performed within 24 hours after symptom onset. Sensitivity of retinal diffusion restrictions declined in the second week (10.0%, P < .001). Absence of retinal diffusion restrictions was more prevalent in patients without fundoscopic retinal edema (60% versus 27.1%, P = .004) and with restitution of visual acuity at discharge (75% versus 28.4%, P = .006). CONCLUSIONS: Retinal diffusion restrictions in acute central retinal artery occlusion can be reliably identified on DWI performed within 24 hours and 1 week after onset of visual impairment. Detectability of retinal diffusion restrictions is dependent on the clinical course of the disease.

An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits.

Patients with abetalipoproteinemia, a disease caused by defects in the microsomal triglyceride transfer protein (MTP), do not produce apolipoprotein B-containing lipoproteins. It was hypothesized that small molecule inhibitors of MTP would prevent the assembly and secretion of these atherogenic lipoproteins. To test this hypothesis, two compounds identified in a high-throughput screen for MTP inhibitors were used to direct the synthesis of a highly potent MTP inhibitor. This molecule (compound 9) inhibited the production of lipoprotein particles in rodent models and normalized plasma lipoprotein levels in Watanabe-heritable hyperlipidemic (WHHL) rabbits, which are a model for human homozygous familial hypercholesterolemia. These results suggest that compound 9, or derivatives thereof, has potential applications for the therapeutic lowering of atherogenic lipoprotein levels in humans.

A plant triterpenoid, avicin D, induces autophagy by activation of AMP-activated protein kinase.

Avicins, a family of plant triterpene electrophiles, can trigger apoptosis-associated tumor cell death, and suppress chemical-induced carcinogenesis by its anti-inflammatory, anti-mutagenic, and antioxidant properties. Here, we show that tumor cells treated with benzyloxycarbonylvalyl-alanyl-aspartic acid (O-methyl)-fluoro-methylketone, an apoptosis inhibitor, and Bax(-/-)Bak(-/-) apoptosis-resistant cells can still undergo cell death in response to avicin D treatment. We demonstrate that this non-apoptotic cell death is mediated by autophagy, which can be suppressed by chloroquine, an autophagy inhibitor, and by specific knockdown of autophagy-related gene-5 (Atg5) and Atg7. Avicin D decreases cellular ATP levels, stimulates the activation of AMP-activated protein kinase (AMPK), and inhibits mammalian target of rapamycin (mTOR) and S6 kinase activity. Suppression of AMPK by compound C and dominant-negative AMPK decreases avicin D-induced autophagic cell death. Furthermore, avicin D-induced autophagic cell death can be abrogated by knockdown of tuberous sclerosis complex 2 (TSC2), a key mediator linking AMPK to mTOR inhibition, suggesting that AMPK activation is a crucial event targeted by avicin D. These findings indicate the therapeutic potential of avicins by triggering autophagic cell death.

School environmental conditions and links to academic performance and absenteeism in urban, mid-Atlantic public schools.

School facility conditions, environment, and perceptions of safety and learning have been investigated for their impact on child development. However, it is important to consider how the environment separately influences academic performance and attendance after controlling for school and community factors. Using results from the Maryland School Assessment, we considered outcomes of school-level proficiency in reading and math plus attendance and chronic absences, defined as missing 20 or more days, for grades 3-5 and 6-8 at 158 urban schools. Characteristics of the environment included school facility conditions, density of nearby roads, and an index industrial air pollution. Perceptions of school safety, learning, and institutional environment were acquired from a School Climate Survey. Also considered were neighborhood factors at the community statistical area, including demographics, crime, and poverty based on school location. Poisson regression adjusted for over-dispersion was used to model academic achievement and multiple linear models were used for attendance. Each 10-unit change in facility condition index, denoting worse quality buildings, was associated with a decrease in reading (1.0% (95% CI: 0.1-1.9%) and math scores (0.21% (95% CI: 0.20-0.40), while chronic absences increased by 0.75% (95% CI: 0.30-1.39). Each log increase the EPA's Risk Screening Environmental Indicator (RSEI) value for industrial hazards, resulted in a marginally significant trend of increasing absenteeism (p < 0.06), but no association was observed with academic achievement. All results were robust to school-level measures of racial composition, free and reduced meals eligibility, and community poverty and crime. These findings provide empirical evidence for the importance of the community and school environment, including building conditions and neighborhood toxic substance risk, on academic achievement and attendance.

A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors.

A series of benzimidazole-based analogues of the potent MTP inhibitor BMS-201038 were discovered. Incorporation of an unsubstituted benzimidazole moiety in place of a piperidine group afforded potent inhibitors of MTP in vitro which were weakly active in vivo. Appropriate substitution on the benzimidazole ring, especially with small alkyl groups, led to dramatic increases in potency, both in a cellular assay of apoB secretion and especially in animal models of cholesterol lowering. The most potent in this series, 3g (BMS-212122), was significantly more potent than BMS-201038 in reducing plasma lipids (cholesterol, VLDL/LDL, TG) in both hamsters and cynomolgus monkeys.

The beliefs and values shaping today's health reform debate.

Survey results show that the American public comes to the health care reform debate with ambivalent feelings and a relatively low base of specific knowledge. But Americans also hold a set of core values that will shape their response to various proposals for national change. These include (1) a moral commitment to the uninsured; (2) a desire to achieve personal peace of mind; (3) a lack of self-blame; (4) a limited willingness to sacrifice; (5) reasoned self-interest in what changes are enacted; (6) a distrust of government; and (7) a healthy cynicism about the behavior of our major institutions.

Isolated fusions of the hindfoot.

Increasingly, isolated arthrodeses are being used to successfully manage disorders of the hindfoot. Their relative simplicity makes these procedures an attractive alternative to the triple arthrodesis. Each joint fusion is not without certain pitfalls, and issues such as the location of the pain, origin, planal dominance, and multiple joint involvement must be taken into consideration when choosing a specific procedure. With proper patient selection and careful technique, the surgeon will find these procedures provide a valuable addition to his/her armamentarium.

The incidence of schizophrenia and severe psychological disorders in patients 10 years after cosmetic rhinoplasty.

Body image disturbance may be an early sign of schizophrenia. The significance of this and dysmorphophobia with relation to patients seeking cosmetic rhinoplasty is discussed. Results of a follow-up of patients 10 years after cosmetic surgery to see whether they developed schizophrenia or serious psychological disorder are presented. The literature, significance of the findings and the clinical implications are all discussed.

Dysmorphophobia--a long-term study.

This study examines the mental health of 187 patients who had a rhinoplasty fifteen years earlier. Of 101 who had the operation following disease or injury 9 are now severely neurotic and one schizophrenic; of 86 who had the operation for aesthetic reasons 32 are now severely neurotic and 6 schizophrenic. The differences between the two groups are significant, and show that dysmorphophobia is an ominous symptom.

Modified arthroscopic excision of the symptomatic os trigonum and release of the flexor hallucis longus tendon: operative technique and case study.

This article presents an operative technique for modified arthroscopic excision of the symptomatic os trigonum and release of the flexor hallucis longus tendon sheath. The procedure uses two stacked posterolateral subtalar joint portals, rather than the customary anterolateral and posterolateral portal combination. By visualizing the os trigonum with an arthroscope positioned in a distal portal and introducing instrumentation through a proximal portal, the ossicle may be quickly exposed and excised with minimal dissection. A case study with a 22-month follow-up and a discussion of os trigonum syndrome are included to illustrate this procedure as an alternative to open excision or traditional arthroscopic excision.

Administration of rocuronium (Org 9426) by continuous infusion and its reversibility with anticholinesterases.

The use of rocuronium (Org 9426) as a single bolus followed by an infusion was assessed in 50 patients under anaesthesia with nitrous oxide-oxygen and halothane. Neuromuscular block was monitored using train-of-four stimulation and recording the force of contraction of the adductor pollicis muscle. Rocuronium was administered in an initial bolus dose of 0.45 mg.kg-1 followed by an infusion adjusted manually to maintain the T1, the first response in the train-of-four, at 10% of control. Following cessation of rocuronium infusion the patients were either allowed to recover spontaneously (n = 10) or were given neostigmine 50 micrograms.kg-1 or edrophonium 1 mg.kg-1 at 10 or 25% recovery of the T1 (n = 10 for each group). Adequate antagonism was defined as attaining a sustained train-of-four ratio of 0.7. Rocuronium requirements showed marked variation among individual patients but were relatively constant in individual patients. The mean (SD) time to attain stable infusion rates was 17.4 (10.9) min. The mean (SD) requirement of rocuronium for steady state 90% block of T1 was 572 (190) micrograms.kg-1.h-1 (range 242-1104 micrograms.kg-1.h-1). The mean (SD) time to attain a train-of-four ratio of 0.7 in the group allowed to recover spontaneously was 36.1 (7.3) min. This interval was 7.5 (1.9), 9.3 (7.0), 4.6 (1.9) and 1.9 (0.9) min respectively in the groups receiving neostigmine at T1 of 10%, edrophonium at T1 of 10%, neostigmine at T1 of 25% and edrophonium at T1 of 25%. The antagonism was significantly faster in those reversed at 25% (p < 0.05). Three patients in the group receiving edrophonium at T1 of 10% and one in the group receiving neostigmine at T1 of 25% failed to attain a train-of-four ratio of 0.7. It is concluded that rocuronium can be administered as a continuous infusion for stable neuromuscular block. Neostigmine may be a more reliable antagonist of deep block, whereas edrophonium is advantageous when there is a greater spontaneous recovery.

Neuromuscular effects of rocuronium in patients receiving beta-adrenoreceptor blocking, calcium entry blocking and anticonvulsant drugs.

We have studied the onset and duration of action of rocuronium 0.6 mg kg-1 in patients receiving therapy for more than 1 month with beta-receptor blocking drugs (n = 16), calcium entry blocking drugs (n = 17) or anticonvulsant drugs (n = 14) and compared these data with those from a control group (n = 27). Anaesthesia comprised fentanyl, propofol infusion and nitrous oxide in oxygen. Neuromuscular block was monitored by measuring the force of contraction of the adductor pollicis muscle in response to train-of-four (TOF) stimulation. There were no significant differences in onset times between the four groups (mean 62-76 s). Mean times to 25% recovery of T1 (first response in the TOF) and of the TOF ratio of 0.7 were 38 (SD 15) and 58 (22) min, 36 (8) and 61 (19) min, 40 (11) and 68 (22) min, and 25 (6) and 35 (9) min in the control, beta-blocker, calcium entry blocker and anticonvulsant groups, respectively (P < 0.01 between the anticonvulsant and other groups). We conclude that chronic therapy with anticonvulsant drugs reduces the duration of action of rocuronium.

A comparison of the effects of isoflurane and desflurane on the neuromuscular effects of mivacurium.

The effects of 1 MAC of desflurane and isoflurane (in 66% nitrous oxide) on the potency and duration of action of mivacurium were studied in 80 patients. The ED95 of mivacurium was 86 micrograms.kg-1 (74-100) and 88 micrograms.kg-1 (76-103) (mean and 95% confidence intervals) during anaesthesia with desflurane and isoflurane respectively. The onset and duration of recovery to 25, 75 and 90% of T1 (first response in the TOF) of 200 micrograms.kg-1 of mivacurium were 1.4 (0.3) and 1.5 (0.3) min (mean and SD), 22 (4.9) and 19 (4.0), 29 (6.6) and 26 (5.8), and 32 (7.3) and 29 (6.6) min respectively. There was no significant difference in any of the variables between desflurane and isoflurane. It is concluded that the neuromuscular effects of mivacurium are similar during anaesthesia with 1 MAC of desflurane and isoflurane.

The influence of the duration of control stimulation on the onset and recovery of neuromuscular block.

The onset of action of atracurium 450 micrograms/kg, mivacurium 160 micrograms/kg, and vecuronium 80 micrograms/kg was measured after train-of-four (TOF) stimulation had been applied for 1, 5, 10, 15, or 20 min in groups of 10 patients each during anesthesia with thiopental, nitrous oxide-oxygen, and fentanyl. TOF stimulation was applied to the ulnar nerve at 2 Hz every 12 s and the force of contraction of the adductor pollicis muscle recorded. There was a progressive and significant reduction in the time to onset of maximum block with increasing times of control stimulation with all three relaxants (P < 0.0001). The mean +/- SD times to onset of maximum block decreased from 224 +/- 103 to 73 +/- 28 s with atracurium, 239 +/- 81 to 101 +/- 33 s with vecuronium, and 198 +/- 72 to 106 +/- 23 s with mivacurium as the period of control stimulation increased from 1 to 20 min. The time to recovery of T1 (first response in the TOF stimulation) to 25% of control (duration of clinical relaxation) increased from 33 +/- 5.7 to 52 +/- 13.4 min with atracurium, 25 +/- 7.6 to 38 +/- 9.4 min with vecuronium, and 13 +/- 2.5 to 18 +/- 3.5 min with mivacurium with the period of control stimulation increasing from 1 to 20 min. The differences were significant for atracurium and vecuronium (P < 0.05-0.0001). We conclude that increasing periods of control stimulation are associated with decreasing time to onset of neuromuscular block with atracurium, vecuronium, and mivacurium at the adductor pollicis muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Talonavicular joint arthrodesis and Evans calcaneal osteotomy for treatment of posterior tibial tendon dysfunction.

The purpose of this study was to evaluate the combination of talonavicular fusion and Evans calcaneal osteotomy for the treatment of posterior tibial tendon dysfunction. This was a retrospective study of 10 patients, mean age 48.7 years, who had continued pain despite 6 months of conservative treatment and a minimum Johnson and Strom stage II deformity. Patients completed a detailed questionnaire, were physically examined, and their postoperative improvement was graded according to the American Orthopedic Foot and Ankle Society Ankle-Hindfoot Rating Scale. At a mean of 35 months (range 8-72 months) after surgery, patients demonstrated a significant improvement (p<.001) both in their subjective discomfort and in the structural alignment and function of their feet. The authors feel that this combination of procedures allows greater correction and stability than either procedure performed alone, and provides a viable alternative to triple arthrodesis.

First metatarsophalangeal arthrodesis for treatment of hallux rigidus: a retrospective study.

This was a retrospective study of 17 patients (21 operated feet) treated with first metatarsophalangeal arthrodesis for hallux rigidus of varying severity levels. Patients were evaluated according to a modified American Orthopedic Foot and Ankle Society hallux metatarsophalangeal-interphalangeal rating scale containing 60 subjective and 30 objective points. At an average follow-up time of 28.1 months, patients demonstrated a mean subjective improvement from 21.2 to 47.8/60, with mean total scores improving from 39.1 to 75.6/90. A comparison of pre- and postoperative radiographic angular measurements demonstrated a significant improvement (p = .001) in intermetatarsal, first metatarsal declination, and lateral talo-first metatarsal angles. Significant positive correlations were found between subjective results and patient age (p = .05) and the preoperative lateral talo-first metatarsal angles (p = .001).