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Background The multifaceted origins of cancer are related to the dynamic interface between the human body and the environment. It is estimated that as many as 60% of cancers arise from environmental exposures. Objectives This article describes potential risks for exposure to radon, arsenic, pesticides, and antineoplastic agents, which can lead to the development of cancer. Methods The authors performed a review of the literature on environmental exposures and their relationship to the development of cancer. Findings Environmental factors are abundant in the home, workplace, and environment. Nurses can lead campaigns to educate the public about environmental risk factors and their effects on the development of cancer.

Summary: Background: We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods: Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings: Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation: This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenges. Funding: The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity, National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The Seva Foundation, British Council for the Prevention of Blindness, and Christian Blind Mission. Translations: For the French, Spanish, Chinese, Portuguese, Arabic and Persian translations of the abstract see Supplementary Materials section.

Antimicrobial resistance in neonatal sepsis is rising, yet mechanisms of resistance that often spread between species via mobile genetic elements, ultimately limiting treatments in low- and middle-income countries (LMICs), are poorly characterized. The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) network was initiated to characterize the cause and burden of antimicrobial resistance in neonatal sepsis for seven LMICs in Africa and South Asia. A total of 36,285 neonates were enrolled in the BARNARDS study between November 2015 and December 2017, of whom 2,483 were diagnosed with culture-confirmed sepsis. Klebsiella pneumoniae (n = 258) was the main cause of neonatal sepsis, with Serratia marcescens (n = 151), Klebsiella michiganensis (n = 117), Escherichia coli (n = 75) and Enterobacter cloacae complex (n = 57) also detected. We present whole-genome sequencing, antimicrobial susceptibility and clinical data for 916 out of 1,038 neonatal sepsis isolates (97 isolates were not recovered from initial isolation at local sites). Enterobacterales (K. pneumoniae, E. coli and E. cloacae) harboured multiple cephalosporin and carbapenem resistance genes. All isolated pathogens were resistant to multiple antibiotic classes, including those used to treat neonatal sepsis. Intraspecies diversity of K. pneumoniae and E. coli indicated that multiple antibiotic-resistant lineages cause neonatal sepsis. Our results will underpin research towards better treatments for neonatal sepsis in LMICs., Genomic and clinical analysis of 916 bacterial isolates from neonates with sepsis in seven low- and middle-income countries (the BARNARDS study) reveals that the main species present were antimicrobial-resistant Klebsiella, Escherichia coli and Enterobacter.

Children abandoned to institutions display a host of developmental delays, including those involving general cognition and language. The majority of published studies focus on children over 3 years of age; little is known about whether these delays may be detected earlier when children undergo rapid lexical development. To investigate the early language development of children raised in institutional settings in the Russian Federation, we compared a group of children in institutional care (n = 36; 8-35 months) to their age-matched peers raised in biological families, who have never been institutionalized (n = 72) using the Russian version of the CDI. The results suggest that institutionalization is associated with pronounced delays in children's early language development with large and robust effect sizes. Among children with a history of institutionalization, these delays are also associated with difficulties in Daily Living skills, communication, and socialization.

Chemotherapy administration in the home setting poses risks to patients, caregivers, and the environment, particularly in the event of spills. Although the response to chemotherapy spills in the hospital setting is vigorous and includes standard disposal practices for contaminated items, the management of spills in the home setting may vary. A standardized method for managing chemotherapy spills at home that includes education and distribution of spill cleanup materials is imperative to reduce these risks.

PURPOSE To evaluate efficacy and survival rates of intraocular pressure (IOP)-lowering effect obtained with phacoemulsification (phaco) alone or in combination with canaloplasty (PCP) in patients with open-angle glaucoma (OAG). METHODS Retrospective chart review of consecutive cases at the Department of Ophthalmology, Indiana University. Visual acuity (VA), IOP, number of medications (Meds), failures, and survival rates of IOP-lowering effect were analyzed. Inclusion criteria were: patients older than 18 years with OAG and cataract. Exclusion criteria were: no light perception vision, prior glaucoma surgery, chronic uveitis, angle-closure glaucoma, and advanced-stage or end-stage OAG. Failure criteria were: IOP>21 mm Hg or

PurposeTo evaluate optic nerve diffusion tensor imaging (DTI) parameters in glaucoma patients and controls, and to correlate DTI parameters with the rim area obtained with Heidelberg retina tomography (HRT) and with the severity of glaucomatous damage using the Glaucoma Staging System.DesignPilot study.MethodsTwenty-seven patients with glaucoma and 12 control subjects underwent DTI and HRT imaging. Main outcome measures included: fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, HRT rim area, and Glaucoma Staging System stage.ResultsIn group comparison, mean diffusivity (1.33 vs. 0.91 μm/ms, P=0.0002), axial diffusivity (1.70 vs. 1.43 μm/ms, P=0.036), and radial diffusivity (1.24 vs. 0.71 μm/ms, P0.05).ConclusionsDTI may be a useful technique for detection and evaluation of glaucomatous damage in the optic nerve, particularly for patients in whom conventional imaging and perimetry are not possible. Future studies are needed to evaluate how DTI parameters change longitudinally with glaucomatous damage within the visual pathways and address cerebrospinal fluid partial volume effects in diffusion tensor quantification, especially for patients with advanced glaucoma stage.

Background Many clients of HIV care and treatment services have unmet contraceptive needs. Integrating family planning (FP) services into HIV services is an increasingly utilized strategy for meeting those unmet needs. However, numerous models for services integration are potentially applicable for clients with diverse health needs. This study developed and tested a ‘facilitated referral’ model for integrating FP into HIV care and treatment in Tanzania with the primary outcome being a reduction in unmet need for contraception among female clients. Methods The facilitated referral model included seven distinct steps for service providers. A quasi-experimental, pre- and post-test, repeated cross-sectional study was conducted to evaluate the impact of the model. Female clients at 12 HIV care and treatment clinics (CTCs) were interviewed pre- and post-intervention and CTC providers were interviewed post-intervention. Results A total of 323 CTC clients were interviewed pre-intervention and 299 were interviewed post-intervention. Among all clients, the adjusted decrease in proportion with unmet need (3%) was not significant (P = 0.103) but among only sexually active clients, the adjusted decrease (8%) approached significance (P = 0.052). Furthermore, the proportion of sexually active clients using a contraceptive method post-intervention increased by an estimated 12% (P = 0.013). Dual method use increased by 16% (P = 0.004). Increases were observed for all seven steps of the model from pre- to post-intervention. All providers (n = 45) stated that FP integration was a good addition although there were implementation challenges. Conclusion This study demonstrated that the facilitated referral model is a feasible strategy for integrating FP into HIV care and treatment services. The findings show that this model resulted in increased contraceptive use among HIV-positive female clients. By highlighting the distinct steps necessary for facilitated referrals, this study can help inform both programmes and future research efforts in services integration.

We aimed to compare plotting accuracy and interpretation of weight gain patterns in average and small infants on road-to-health (RTH) and the new World Health Organization (WHO) growth charts in Enugu, Nigeria. Child health staff plotted standard weights on both formats. Twelve plotted charts were created, permutating three different weight trajectories (fast, steady, and slow) ending at two attained weights (average and small), with each plotted on both chart formats. Respondents were shown four of these charts and asked to describe the weight gain pattern shown and what action this pattern would prompt. There were 222 respondents, of whom 78% were hospital based; 54% were nurses, 32% medical doctors, and 13% nutritionists. Plotting accuracy was good on both the WHO and RTH charts, but rating of weight gain was generally poor. On the RTH chart, slow weight gain was correctly recognized in only 19% average and 35% small infants, and responses were not significantly associated with the pattern shown. On the WHO charts, slow weight gain was correctly recognized in 40% average and 65% small infants (p = .002 and

Glaucoma is the second most common cause of world blindness (following cataract) with estimated cases reaching 79.6 million by 2020. Although the etiology of glaucoma is multi-factorial, intraocular pressure (IOP) is the only modifiable factor in glaucoma management proven to alter the natural course of the disease. Among various classes of IOP-lowering medications currently available, alpha-adrenergic receptor agonists are used either as monotherapy, as second-line therapy, or in fixed combination with beta-blockers. Non-selective adrenergic agonists such as epinephrine and dipivefrin are infrequently used today for the treatment of glaucoma or ocular hypertension, and have been replaced by the alpha-2-selective agonists. The use of apraclonidine for IOP reduction in glaucoma or OHT is limited due to a high rate of follicular conjunctivitis. The alpha-2-selective agonist in use today is brimonidine. The brimonidine-purite formulations are preferred to brimonidine-benzalkonium chloride (BAC) formulations due better tolerability while maintaining similar efficacy. Brimonidine is also effective when used in combination with a beta-blocker. Using brimonidine-timolol fixed combination (BTFC) as first-line therapy has an added potential for neuroprotection. This would be a valuable strategy for glaucoma treatment, for patients who are intolerant of prostaglandin analogs, or for patients where prostaglandin analogues are contraindicated as first-line therapy, such as in patients with inflammatory glaucoma.

HIV/AIDS disease is endemic in Nigeria and associated with stigmatization. Availability of a reliable rapid testing kit and procedure will increase uptake of services. The study aimed to determine the correlation between detection of HIV antibodies in blood to that in oral fluid and to determine the sensitivity and specificity of the Dual Path Platform (DPP) testing kit using oral fluid samples. HIV antibodies detected in oral mucosa transudate and whole capillary blood from HIV-positive, high-risk and low-risk participants were compared with results obtained with whole venous blood from the same participants tested with Determine and Western blot (for discordant cases). Oral fluid test has sensitivity and specificity of 100% relative to Determine rapid assay, while whole capillary blood test has sensitivity of 100% and specificity of 99.5%. DPP oral fluid test is a reliable point-of-care test and may be deployed in large-scale screening exercises.

In glaucoma, retinal nerve fiber layer (RNFL) thinning results from progressive loss of retinal ganglion cell (RGC) axons. It is now possible to obtain in vivo measurements of the RNFL thickness. For example, optical coherence tomography (OCT) uses light and interferometry to determine the depth of surfaces differing in reflectance much in the way sonar or ultrasound uses sound.1–4 The commonly used time domain OCT technique measures RNFL thickness along a circular path around the optic disc. Various measures of the resulting RNFL thickness profile can be compared to normative data to determine whether the RNFL is abnormally thin. Measures based upon OCT RNFL thickness generally show good sensitivity and specificity for detecting glaucomatous damage.5–19 However, there is considerable inter-subject variation in the RNFL thickness profiles, even among normal controls. For example, although the RNFL profiles from the two eyes of an individual are very similar,20,21 the profiles differed markedly in both amplitude and waveform across individuals.22 If inter-individual variability can be reduced, it should be possible to improve the sensitivity and specificity of tests based upon OCT RNFL thickness. Recent evidence suggests that the location of the superior and inferior temporal blood vessels (BVs) may account for a portion of the inter-subject variability.22 In particular, the location of the major peaks in the RFNL profiles coincide with the approximate location of the superior and inferior temporal BVs. In part, this is due to the direct contribution of these BVs to RNFL thickness as measured by OCT22–24 and, in part, due to the correlation between the location of these BVs and the location of the arcuate bundles.23 We have previously suggested that adjusting for the location of these BVs might decrease variability among controls.22 In the present study, we tested this hypothesis by adjusting RNFL profiles based upon the position of the superior and inferior temporal BVs.

To compare the agreement, sensitivity, and specificity of the Heidelberg Retina Tomograph III Glaucoma Probability Score (GPS) and Moorfields Regression Analysis (MRA) across the spectrum of glaucomatous visual field (VF) loss.Retrospective observational study.Data from 247 glaucoma patients and 142 controls who underwent standard achromatic perimetry (SITA-SAP) and Heidelberg Retina Tomograph III imaging within 6 months were analyzed. Sensitivity, specificity, agreement, and discrimination capability of MRA and GPS were assessed.Age-adjusted specificity was 92% and 93% and sensitivity was 76.88 and 80.85 for GPS and MRA, respectively. Sensitivity for early VF loss [mean deviation (MD)-5 dB] (N=81) was 66.64% and 69.82%, for moderate VF loss (-5 dBMD-15 dB) (N=104) was 78.91% and 85.13%, and for advanced VF loss (MD-15 dB) (N=62) was 87.70% and 86.48% (GPS and MRA, respectively). Age-specific receiver operating characteristics ranged from 0.89 to 0.92 and from 0.87 to 0.90 (GPS and MRA, respectively). Kappa ranged from 0.64 to 0.77.Specificity for MRA and GPS was similar and agreement was good. GPS offered slightly higher age-specific receiver operating characteristic. GPS, which does not require contour line placement, may have a potential role in screening for severe glaucomatous damage.

Objective To compare the diagnostic accuracy of the Moorfields regression classification (MRC) and subjective optic disc evaluation in discriminating early to moderate glaucomatous from nonglaucomatous eyes. Design Cross-sectional observational study. Participants Two hundred thirty-three patients with glaucoma and 216 normal subjects were included in the analysis. Racial groups were defined by self-description. Methods All subjects underwent confocal scanning laser ophthalmoscopy, stereophotography, and standard perimetry. Glaucoma was defined by visual field defect alone and confirmed with a second visual field test. Stereo photographs were graded as either normal or glaucomatous appearing in a masked fashion by 2 independent graders and adjudicated by a third grader in cases of disagreement. Mean disc area was compared between patients correctly and incorrectly diagnosed with either technique. Main Outcome Measures Sensitivity and specificity of MRC and subjective evaluation of stereophotographs in the detection of glaucomatous visual field loss. Results With the MRC, the sensitivity and specificity were higher using the 95% cutoff than using the 99.9% cutoff. Classification based on subjective photo assessment had a greater agreement with the diagnosis of glaucoma than the MRC for blacks (MRC, sensitivity=62.5%, specificity=93.2%; Photo, sensitivity=76.5%, specificity=91.5%) and whites (MRC, sensitivity=67.0%, specificity=92.2%; photo, sensitivity=78.4%, specificity=91.9%). Disc area was significantly larger in patients incorrectly diagnosed with the MRC ( P = 0.0289). Conclusions Subjective optic disc grading by glaucoma specialists outperformed the MRC with the HRT II in both black and white subjects. Both subjective and objective diagnostic methods were associated with similar sensitivity and specificity between racial groups. The MRC was more likely to provide an incorrect diagnosis in subjects with larger optic discs.

Purpose To compare the level of agreement between subjective and objective methods in estimating horizontal and vertical cup-to-disc ratios (HCDR and VCDR, respectively) to determine if objective techniques may be used as surrogates for subjective cup-to-disc (CDR) estimation. Methods Fifty-one glaucoma patients and 49 control subjects underwent full ophthalmic examination, stereoscopic optic nerve head photographs (ONHPs), confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomography II [HRT II]), and optical coherence tomography (Stratus OCT). The intraclass correlation coefficient (ICC) and Bland Altman plots were used to assess the agreement across the three methods. Repeated measures analysis of variance (ANOVA), Tukey adjustment, and pairwise P values were used to compare the HCDR and VCDR estimates between three clinicians who reviewed photos, Stratus OCT, and HRT II. Results For the clinicians, the agreement in subjectively assessed HCDR and VCDR was substantial (ICC=0.84 and 0.85, respectively), and for all three methods, overall agreement was good (ICC=0.75 and 0.77 for the HCDR and VCDR, respectively). Stratus OCT provided the largest overall mean+/-SD HCDR (0.68+/-0.14) and VCDR (0.62+/-0.13). The smallest overall mean+/-SD HCDR was provided by ONHP (0.32+/-0.16), and the smallest overall mean+/-SD VCDR was provided by HRT II (0.26+/-0.20). Repeated measures ANOVA test demonstrated significant differences across the three methods for glaucomatous (P=0.0017 and 0.0016, HCDR and VCDR, respectively) and normal (P=0.0001 for both HCDR and VCDR) eyes. Tukey adjustment demonstrated specific statistical differences between pairs of methods. Conclusions Although the overall agreement between various methods was good, the mean estimates were statistically different. Additional studies are needed to evaluate the sources of variability, their level of significance, and longitudinal agreement between various methods of the CDR estimation.

The appropriateness of the initial pathway to care, especially eye care, is critical for timeliness and outcomes of care. Individual-dependent and health system-determined factors influence the preferred initial pathway to care. This study aimed to map the initial pathways to eye care in a rural population in south-east Nigeria and identify the associated factors.This study was a population-based, cross-sectional descriptive survey conducted in Abagana, a rural south-east Nigeria community, in September 2011. Using a researcher-administered questionnaire, data on participants' sociodemographics, preferred initial eyecare pathway when confronted with an eye disorder and their reason(s) for the choice of pathway were collected. Descriptive and analytical statistics were performed. Regression analysis was used to identify independent predictors of visiting an ophthalmologist when confronted with an eye disorder. In all comparisons, p0.05 was considered statistically significant.The participants (n = 501: 263 men; 238 women) were aged 48.9±16.3 years (range 18-93 years). The majority of the participants were married (339; 67.7%) and possessed formal education (415; 82.8%). The participants' frequently preferred initial pathways to eye care were to consult a patent medicine dealer (178; 35.0%), to consult an ophthalmologist (165; 33.0%), and to self-medicate (125; 25.0%). Possession of formal education (odds ratio 0.3; 95% confidence interval 0.1-0.5; p0.001) was the only significant sociodemographic predictor of consulting an ophthalmologist when confronted with an eye disorder The participants' main reasons for not consulting an ophthalmologist were ignorance (190; 56.5%), cost (199; 59.2%), and restricted spatial access (228; 67.9%).The majority of the respondents chose an inappropriate eyecare pathway in the event of an eye disorder. The reported barriers to appropriate pathway selection are amenable to community-based eye health education, enhanced affordability, and even distribution of eyecare services. Integrating other alternative care pathways into orthodox eye care should be considered.

Background The World Health Organisation has recommended the use of anthropometric measurements as birth weight surrogates. However, it has been found that cut-off points for these anthropometric measurements vary across nations and ethnic groups. Objectives To determine the predictive values of chest circumference (CC), occipito-frontal circumference (OFC) and their combinations for low birth weight (LBW) detection in Igbo newborns. Methods Live newborns of Igbo origin were recruited within 24 hours of delivery. Their CC, OFC and weight were measured. Cut off points for predicting low birth weight was determined using ROC analysis. Results A total of 511 live newborns were recruited. For birth weight

Scedosporium prolificans is a soil saprophyte that is associated with a large variety of infectious processes and with respiratory colonization in immunocompetent and immunocompromised patients. We report the first described case of S. prolificans keratouveitis associated with the intraocular long-term retention of a contact lens in a 76-year-old female patient.

Purpose To report a case and management of uveitis-glaucoma-hyphema (UGH) syndrome and corneal decompensation associated with cosmetic iris implants. Design Interventional case report. Methods settings: Department of Ophthalmology, University of Minnesota School of Medicine. patients: A 29-year-old man presented with bilateral redness, severe pain, photophobia, and reduction in visual acuity. Examination revealed intraocular pressure (IOP) of 38 mm Hg and 40 mm Hg right and left eye respectively, bilateral conjunctival injection 3+, epithelial corneal edema, microhyphema, cells 3+ to 4+ and flare 2+, bilateral cosmetic iris implants, and surgical peripheral iridectomies. The patient was diagnosed with UGH syndrome and corneal decompensation associated with cosmetic iris implants. intervention: Immediate medical management of inflammation and elevated IOP, anterior segment imaging, specular microscopy, Humphrey 24-2 visual field (VF) testing; following failed conservative management, combined trabeculectomy and removal of the iris implants. main outcome measures: Anterior chamber inflammation and microhyphema, IOP, and corneal edema. Results Anterior segment imaging demonstrated bilateral implant-iris apposition and implant-angle structures apposition. Specular microscopy demonstrated a significant reduction of the number of endothelial cells. VF test demonstrated a right superior arcuate scotoma and a normal left VF. Following surgical treatment IOP normalized and inflammation and microhyphema subsided. However, mild corneal edema persisted. Conclusion Cosmetic iris implantation may lead to UGH syndrome and corneal decompensation. Therefore, its use should be reserved for patients with significant medical indications, and avoided in patients with intact natural iridies, until more short-term and long-term safety data are available.

Background and Objective:To evaluate the intra-observer and inter-observer reproducibility of anterior chamber depth (ACD) and central corneal thickness (CCT) measurements taken by slit-lamp–adapted optical coherence tomography (SL-OCT) and to evaluate concordance of CCT and ACD values obtained by SL-OCT with gold standard devices.Patients and Methods:Three images of each eye were taken by two different operators using SL-OCT. ACD and CCT values obtained by each operator were determined and compared to one another and to ultrasonic pachymetry (CCT) and axial OCT biometry (ACD) values obtained by a third, masked operator. Intra-observer and inter-operator reproducibility was assessed using the intraclass correlation coefficient (ICC).Results:Forty-one eyes of healthy subjects were enrolled. Mean CCT was 0.556 ± 0.020, 0.557 ± 0.019, and 0.532 ± 0.032 and mean ACD was 3.12 ± 0.36, 3.13 ± 0.38, and 3.50 ± 0.44 for operators 1, 2, and 3, respectively (P < .001, for both CCT and ACD). Intra-operator reproducibility for CCT (ICC of 0.948 to 0.995) and ACD (ICC of 0.972 to 0.987) was excellent.Conclusion:SL-OCT provides highly reproducible measures for both CCT and ACD. SL-OCT yields higher values for CCT compared to ultrasonic pachymetry and lower values for ACD compared to axial OCT biometry. Caution should be taken when extrapolating these data into clinical practice until the differences between SL-OCT, axial OCT biometry, and ultrasonic pachymetry can be further elucidated.

Purpose To understand better the influence of retinal blood vessels (BVs) on the interindividual variation in the retinal nerve fiber layer (RNFL) thickness measured with optical coherence tomography (OCT). Subjects and methods RNFL thickness profiles were measured by OCT in 16 control individuals and 16 patients. The patients had advanced glaucoma defined by abnormal disc appearance, abnormal visual fields, and a mean visual field deviation worse than -10 dB. Results In general, the OCT RNFL thickness profiles showed 4 local maxima, with the peak amplitudes in the superior and inferior regions occurring in the temporal (peripapillary) disc region. There was considerable variability among individuals in the location of these maxima. However, the 4 maxima typically fell on, or near, a major BV with the temporal and inferior peaks nearly always associated with the main temporal branches of the superior and inferior veins and arteries. In the patients' hemifields with severe loss (mean visual field deviation worse than -20 dB), the signals associated with the major BVs were in the order of 100 to 150 microm. Conclusions The variation in the local peaks of the RNFL profiles of controls correlates well with the location of the main temporal branches of the superior and inferior veins and arteries. This correspondence is, in part, due to a direct BV contribution to the shape of the OCT RNFL and, in part, due to the fact that BVs develop along the densest regions of axons. Although the overall BV contribution was estimated to be relatively modest, roughly 13% of the total peripapillary RNFL thickness in controls, their contribution represents a substantial portion locally and increases in importance with disease progression.

Though many studies have examined the role of CB2 receptors in immune cell migration, it has been difficult to form definitive conclusions about the physiopathological role of these receptors in regulating immune responses and how this might be pharmacologically targeted for therapy. Do cannabinoids promote inflammation through the recruitment of immune cells, or reduce inflammation by interfering with the action of other chemoattractants? Is therapeutic intervention with an agonist or antagonist more appropriate for the reduction of inflammation? In this review, we will summarize the progress that has been made in answering these questions and outline current hypotheses.

Studies evaluating the reproducibility of recent versions of the confocal scanning laser ophthalmoscope (HRT-II; Heidelberg Engineering, Heidelberg, Germany), scanning laser polarimetry (GDx-VCC; Carl Zeiss Meditec, Inc., Dublin, CA), and optical coherence tomography (StratusOCT; Carl Zeiss Meditec, Inc.) have shown that each of these imaging techniques obtains measurements with a high degree of reproducibility.1–5 However, most of these studies were performed in healthy eyes or in eyes of patients with glaucoma with predominantly early field loss and did not include cases with more advanced stages of field loss.3,5–7 Hence, evaluation of reproducibility for glaucoma cases has been performed in cohorts with a truncated range of field loss ranging from none to early loss, and reproducibility is unknown in cases with more advanced field loss. Although it has been argued that observation and documentation of the optic disc becomes less important at more advanced stages of disease, this has never been rigorously evaluated with subjective and objective techniques. Furthermore, the “floor” effect in cases of advanced glaucoma also impairs the utility in visual fields, which become increasingly variable in advanced disease.8,9 Indeed, no validated technique has been developed to observe patients with advanced glaucoma. Although a floor effect has been reported using GDx-VCC in eyes of patients with end-stage glaucoma,8 it is unknown whether a similar effect is likely to be present in less damaged eyes with severe field loss and good central visual acuity. In addition, higher test–retest variability of the confocal scanning laser ophthalmoscope (HRT) has been reported in locations of the optic disc topography with steep contour, such as the optic disc cup.10 Thus, test–retest variability is likely to be altered by variation in the surface contour of the optic disc as the disease advances. The purpose of the study was to determine and compare the effect of degree of field loss on the repeatability (two replicated scans) of nerve fiber layer measured with GDx-VCC and StratusOCT and on optic nerve head (ONH) topography measured with HRT-II and StratusOCT within the same study population of healthy eyes and glaucomatous eyes with diverse degrees of field loss.

In an effort to detect and document changes indicative of glaucoma at earlier stages, a variety of techniques have evolved to provide quantitative estimates of optic nerve head (ONH) topography, retinal nerve fiber layer (RNFL) thickness, and macular thickness. Several studies have demonstrated that in prior versions each of some of these techniques discriminate between glaucomatous and normal populations with a high degree of sensitivity and specificity.1–5 However, few studies have compared the diagnostic performance of these instruments in the same study population and in comparison to subjective assessment of the ONH.1,3 These prior studies used older versions of the instruments and demonstrated that objective optic nerve imaging modalities were equivalent to subjective assessment performed by masked expert stereophotograph graders. Since the earlier studies, significant modifications have occurred with each of these quantitative imaging techniques that have improved their ability to detect glaucomatous damage. With scanning laser polarimetry (GDx-VCC; Carl Zeiss Meditec, Inc., Dublin, CA), a conversion to variable corneal compensation that provides individualized adjustment of anterior segment birefringence has improved the sensitivity and specificity of this technique.6,7 The current generation of optical coherence tomography (StratusOCT; Carl Zeiss Meditec, Inc.) has increased scan rate and scan resolution and can also be used to obtain macular and ONH measurements.8 The most recent version of the confocal scanning laser ophthalmoscope (HRT II; Heidelberg Engineering, Heidelberg, Germany) has been modified significantly with automation of the examination procedure focused on optic disc topography, which has improved the reproducibility and efficacy of this instrument in the detection of glaucoma.2,4,9,10 A recent study by Medeiros et al.11 using the current version of these instruments has demonstrated that each performs with similar efficacy in the diagnosis of glaucoma. However, there was no comparison between these new versions of objective imaging methods with subjective ONH evaluation or objective evaluation of the optic nerve head with ONH analysis and macular thickness from StratusOCT. The purpose of this study was to compare the diagnostic ability of the confocal scanning laser ophthalmoscopy with the HRT II, scanning laser polarimetry with the GDX-VCC, and retinal nerve fiber layer thickness, ONH analysis and macular thickness measurements with the StratusOCT with subjective masked expert assessment of stereophotographs in the same study population.

Purpose To evaluate correlations between retinal nerve fiber layer (RNFL) thickness with visual field (VF) sensitivities in eyes with nonartertic anterior ischemic optic neuropathy (NAION). Design Case-control study in an academic, institutional setting. Methods One eye from 21 patients with NAION and 32 healthy participants were included in this prospective study. Humphrey visual field (HVF) sensitivities were obtained from standard achromatic HVF test (24-2 SITA). RNFL was measured with scanning laser polarimetry (SLP, GDx-VCC) and optical coherence tomography (OCT, StratusOCT). Correlations were evaluated between RNFL and sensitivities from global, hemifields, and regional locations of the VF pertinent to the RNFL distribution. A total of 15 NAION eyes had inferior altitudinal HVF defects, and their global and regional RNFL was compared with that of control eyes. The main outcome measure was correlation between HVF sensitivities and RNFL. Results Correlations of global, hemifield, and sectorial HVF sensitivities with RNFL were greater when RNFL was measured with OCT than with SLP, except for nasal and inferonasal sectors. RNFL thickness was far lower in the hemiretinas corresponding to the relative unaffected hemifield in eyes with altitudinal VF defect compared with controls. Conclusions In patients with NAION, RNFL measured by OCT provided better correlation to HVF changes than SLP did. Both instruments showed decreased RNFL in NAION eyes with altitudinal VF defects compared with control eyes, demonstrating loss of RNFL even in sectors of the optic disk that corresponded to relatively unaffected hemifield, suggesting greater damage beyond the extent estimated by VF methods.

Purpose To report acute angle-closure glaucoma in a patient with dense vitreous hemorrhage due to a ruptured retinal arterial macroaneurysm. Design Interventional case report. Methods A male patient presented with severe pain and decreased vision in his right eye, nausea, and vomiting. Visual acuity was hand motions, intraocular pressure was 64 mm Hg, and light reflex was not detected in the right eye. The patient underwent comprehensive ophthalmologic examination and appropriate medical and surgical management. Results Examination of the right eye revealed a shallow anterior chamber and closed angle; ultrasound confirmed the presence of vitreous hemorrhage. After intensive medical treatment and subsequent pars plana vitrectomy with laser treatment to the ruptured retinal macroaneurysm, pain in the right eye subsided, visual acuity improved to 20/25, and intraocular pressure decreased to 20 mm Hg. Conclusion We are unaware of previous clinical reports of this finding and could find no reference to it in a computerized search utilizing MEDLINE. In our patient the pressure stabilized and the vision improved after medical and surgical management.

Objective To report 25 cases of gradual, but sometimes progressive, late-postoperative degeneration of polymethyl methacrylate (PMMA) optics of posterior chamber (PC) intraocular lens (IOL) implants, often resulting in a clinically significant visual decrease long after the implantation, sometimes to a severity that required IOL explantation/exchange. Design Analysis of explanted PC IOLs, clinical histories, and photographs. Participants We analyzed 25 case histories/photographs and/or explants from 18 patients implanted in the 1980s to mid-1990s with three-piece PC IOLs with PMMA optics and with polypropylene or PMMA haptics. The IOL optic from each case had characteristic snowflake or crystalline opacifications. This condition occurred with more than one manufacturer and in some cases was restricted to certain lot numbers. Methods The explanted IOLs (n = 10) were studied by gross inspection and by light and scanning electron microscopy, as well as confocal and energy dispersive spectroscopy. Main outcome measures The snowflake lesions were noted within the IOL optics. The nature of these lesions was investigated. Results Assimilation of clinical information with pathologic and morphologic profiles of all cases suggested that the snowflake opacification was a small spherical lesion surrounded by an outer pseudocapsule composed of compressed, degenerated PMMA, with a central core containing convoluted fragments of PMMA. The lesions were classified into four clinical and pathologic grades according to their density and severity. Conclusions This is the first clinicopathologic correlative report on this complication. We postulate that manufacturing variations in some IOL models fabricated in the 1980s and early 1990s are responsible. The snowflake lesions seem to represent a destruction of the PMMA material. The cluster of lesions in implanted lenses manufactured by Surgidev was less progressive than some other models, including lenses made by IOPTEX Research Corporation. This identification of a condition previously unreported is important to alert clinicians regarding these perplexing lesions that may otherwise be considered idiopathic, with no obvious clinical hint as to their origin. The prevalence noted thus far is still too low to in any way suggest that this condition would occur in 100% of PMMA IOLs from these manufacturers. However, these late-occurring lesions, present in lens models that were implanted in hundreds of thousands of patients in the last decade or so, could have constituted a true epidemic, except that many of the patients are now deceased.

As of December 31, 2000, the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser posterior capsulotomy rate for the Alcon AcrySof intraocular lens (IOL) as measured in our database was 3.3%. This was the lowest of any IOL model used in the United States. Only 12 of 361 cases required treatment. We analyzed possible surgical reasons that may have been responsible for the posterior capsule opacification (PCO) in this small group. Special attention was given to the three surgical factors that we had previously identified as being important for PCO reduction: (1) quality of cortical clean up, (2) type of haptic fixation, and (3) continuous curvilinear capsulorhexis (CCC) size and shape.Comparative autopsy tissue analysis.Three hundred sixty-one human eyes obtained postmortem with Alcon AcrySof IOLs, accessioned between January 1995 and December 2000 from Lions Eye Banks.The eyes were evaluated by the Miyake-Apple posterior photographic technique.The area and intensity of Soemmering's ring and type of fixation were studied in 361 eyes. The size and shape of the CCC and relation of the CCC edge to the IOL's optic rim were analyzed in 168 eyes.The amount of Soemmering's ring formation was significantly larger in the group of IOLs requiring Nd:YAG capsulotomy (Nd:YAG group). The not in-the-bag fixated IOLs required more Nd:YAG capsulotomies. Although the trend was clear, the number of specimens was not large enough to acquire statistical significance. The Nd:YAG group showed a highly significant difference compared with the No Nd:YAG group with regard to the amount of clock hours of the CCC edge on the optic rim's surface (P0.001). Mean CCC diameters were significantly larger in the Nd:YAG group (P0.05).The amount of Soemmering's ring correlates with the quality of cortical clean up. Cells within the Soemmering's ring are the direct precursors of PCO. This study confirms our previous laboratory studies and the clinical assumption that the incidence of PCO and thus the need for Nd:YAG capsulotomy is correlated with the cortical clean up. A second clinical assumption, that poor IOL fixation increases the risk of PCO, is also strongly suggested in this study. This study also verifies the relation of the CCC to PCO and the Nd:YAG laser, namely that a relatively small CCC without tears is best to prevent this complication. Use of a high-quality IOL combined with diligent attention to these three surgical factors should lower further the incidence of PCO.

Malaria infection in pregnancy has serious health consequences among mothers and offspring. The influence of placental malaria infection on foetal outcome was studied in a Gambian rural setting where few pregnant women take antimalarial chemoprophylaxis. During July-December 1997, three hundred thirteen mother-newborn pairs (singletons only) were consecutively recruited into a study of the effects of placental malaria infection on the outcome of pregnancy. Placental blood and tissue were collected at delivery. Babies were clinically assessed until discharge. The overall prevalence of placental malaria infection was 51.1% by placental histology and 37.1% by blood smear. The primigravid women were more susceptible to placental malaria than the multigravidae (65.3% vs 44.7%, p=0.01). Placental malaria was significantly associated with pre-term deliveryand intrauterine growth retardation (p0.01), and there was a four-fold risk of delivering low-birth-weight babies if mothers had parasitized placentae [OR=4.42, 95% confidence interval (CI) 2.10-9.27]. A reduction of mean birth-weight of babies by 320 g was associated with placental malaria infection (p0.001). Similarly, a two-fold risk of stillbirth delivery (OR=2.22, 95% CI 1.04-4.72) was observed among the infected mothers. The findings showed that there was still an overall poor foetal outcome associated with placental malaria infection. The findings of this study confirm the findings of an earlier study by McGregor in the Gambia that the low birth-weight rate is significantly higher if the placenta is parasitized. In addition, this study observed that the high stillbirth and prematurity rates were associated with placental malaria infection. The findings of the present study suggest undertaking of effective malaria-control strategies during pregnancy, such as use of insecticide-impregnated bednets, intermittent and early treatment for malaria, and antimalarial chemoprophylaxis, in the Gambia.

An anthropological approach was employed to investigate the universe of representations (ways of thinking) and behaviors (ways of acting) associated with Chagas disease in a group of public service workers in Belo Horizonte (both infected and not infected with Trypanosoma cruzi). An attempt was also made to evaluate the repercussions of this universe of representations and behaviors on the lives of the infected individuals. The collection and analysis of the data followed the "systems of signs, meanings, and actions" model developed by Corin et al. (1989, 1992). Sixteen seropositive and 12 seronegative workers were interviewed to compare their ways of thinking and acting towards the disease. Data analysis allowed identification of diverse elements within a context that maximized the limitations imposed by Chagas disease. These should be taken into account in the planning of educational campaigns and elaboration of health care models for Chagas patients.

To compare the diagnostic accuracy of the Moorfields regression analysis (MRA), parameters, and glaucoma probability score (GPS) from Heidelberg Retinal Tomograph (HRT) 3 (Heidelberg Engineering, Heidelberg, Germany) with MRA and parameters from HRT II in discriminating glaucomatous and healthy eyes in subjects of African and European ancestry.Case-control institutional setting.Seventy-eight glaucoma patients (44 of African ancestry, 34 of European ancestry) and 89 age-matched controls (46 of African ancestry, 33 European ancestry), defined by visual fields and self-reported race were included. Imaging was obtained with HRT II, and data were exported to a computer with the HRT 3 software using the same contour line. Area under the receiver operating characteristic (ROC) curves (AUCs), sensitivity, and specificity were evaluated for the entire group, the African ancestry group, and the European ancestry group separately. Mean disk area was compared between correctly and incorrectly diagnosed eyes by each technique.Disk, cup, and rim areas from HRT 3 were lower than HRT II (P.0001). AUC (sensitivity at 95% specificity) was 0.85 (54%) for vertical cup-to-disk ratio (VCDR) HRT 3, 0.84 (45%) for VCDR HRT II, and 0.81 (44%) for GPS at the temporal sector. MRA HRT 3 showed greater sensitivity but lower specificity than HRT II for the entire group, the African ancestry group, and the European ancestry group. GPS classification had the lowest specificity. Glaucomatous eyes incorrectly classified by GPS had smaller mean disk area (P = .0002); control eyes incorrectly classified had greater mean disk area (P = .015).VCDR from HRT 3 showed higher sensitivity than HRT II and GPS for the entire group and for those of African ancestry and of European ancestry separately. Sensitivity of MRA improved in HRT 3 with some trade-off in specificity compared with MRA of HRT II. GPS yielded erroneous classification associated to optic disk size.

Objective To compare the ability of 24-2 frequency-doubling perimetry (FDP-Matrix) with standard automated perimetry with the Swedish interactive threshold algorithm (SAP-SITA) in detection of visual function abnormalities in patients with glaucomatous-appearing optic discs (GAOD). Methods This observational case-control study included 80 patients with GAOD and 54 control subjects diagnosed by masked assessment of optic disc stereoscopic photographs. Abnormal visual function at SAP-SITA and FDP-Matrix testing required consistent abnormalities in 2 visual field examinations, determined using the glaucoma hemifield test outside 99% normal limits, pattern standard deviation outside 95% normal limits, or 3 contiguous points in the pattern deviation probability plot outside 95% normal limits (at least 1 P Results The FDP-Matrix and SAP-SITA detected abnormal visual function in 51% and 44%, respectively, of GAOD eyes ( P = .26), and both perimetry techniques identified 11% of healthy eyes as abnormal. Agreement between FDP-Matrix and SAP-SITA was moderate (κ = 0.49), as only 35% of GAOD eyes and 2% of healthy eyes had both visual field test results flagged as abnormal. Conclusions The FDP-Matrix detected abnormal visual function in more eyes with GAOD than did SAP-SITA, although this difference was not significant. Each visual field test tended to identify different subsets of eyes with GAOD as abnormal. Combination of these perimetry techniques may improve the detection of visual function abnormalities in patients with glaucoma.

The immunoperoxidase technique after trypsinization was used on paraffin sections of 24 lymph nodes with reactive lymphadenitis and abudant nests of T-associated plasma cells. These cells were negative for all the markers investigated, which were: intracytoplasmic immunoglobulins (CIg), a1-antichymotrypsin(a1 -ACT), a1 -antitrypsin (a1 -AT), lysozyme(Lz) and fibronectin. Other categories of cells were positive or negative depending on their type. The best markers for polymorphs proved to be a1-AT and Lz, and for monocytes and histiocytes a1-ACT and Lz. Sinus histiocytes in particular were much more constantly and strongly positive for a1-ACT than for Lz. Endothelial cells appeared almost always positive for a1-ACT and were also occasionally positive for a1-AT. Fibronectin was consistently positive in mast cells and sometimes positive in other cells, especially those of monihistiocytic origin. Our present findings are against a B-cell or monohistiocytic origin for T-associated plasma cells.

A case of a female infant with karyotype 46,XX,r(21)/45,XX,-21 is reported. From comparison of the phenotypic anomalies with the other similar cases the large variability of the 21q- syndrome is evident.

In order to evaluate the late results of reconstructive surgery for renovascular hypertension, a review was made on a series of 120 consecutive patients who underwent operations over a 11 year period. There were 82 males (68.3%) and 38 females (31.7%) with a mean age of 48.4 years. Renal artery by-pass grafts were used in 90% (120/133), a thromboendarterectomy in 5.2% (7/133), and other surgical procedures were performed in 4.8% (6/133). Associated vascular procedures were performed in 38.3% (46/120) of patients. Operative mortality was 2.5% (3/120) overall; there was no mortality in the isolated renal artery reconstructions. There was a clinical success (after a mean follow-up of 48 months) in 80.4% of patients. The most important factors influencing clinical result after renal revascularization were: a generalized atherosclerosis (p less than 0.05), duration of hypertension (p less than 0.01) and the early post-operative response of the blood pressure (p less than 0.01). The overall five- and ten-year actuarial survival probabilities were 85 and 68%, respectively. The most common causes of death were myocardial infarction, stroke and cancer. Cox regression analysis for variables influencing survival indicated that persistence of severe hypertension was the major determinant of late survival (p less than 0.05). Hypertension in females is better tolerated, while younger patients appear to have better results and late survival after surgical treatment.

In patients with aortoiliac disease and a stenosis of one or two renal artery, renal hypertension is rarely the sole mechanism of the elevated blood pressure. The preservation of nephron mass being the aim of the renal revascularization, we firmly believe that only three tests are required for the operative decision: renal ultrasonography, nephroscintigraphy and global and selective aortography.

The activity of LCAT (the controlling enzyme for cholesterol esterification in plasma) is known to be reduced in alcoholic cirrhosis, while little is known about early stage (liver steatosis) alcoholics. In this study, LCAT activity was assayed by Stokke and Norum's method, before and after a 15-day sobriety period, in liver steatosis and in cirrhosis alcoholics. Before alcohol withdrawal, LCAT activity was depressed in both groups. After the sobriety period, LCAT activity was significantly raised in liver steatosis patients, but was still lower than in controls; in cirrhosis patients, it was increased, but not significantly. According to our results, LCAT activity impairment in alcoholic liver disease is sustained by both the hypothesized mechanisms, alcohol-related metabolic disorders and lowered LCAT-enzyme production, but to different degrees, depending on the stage of the disease. In liver steatosis, metabolic disorders play a major role, as a liver-impairment-induced decrease in LCAT production seems rather unlikely, and increased LCAT activity is more likely to be sustained by metabolic normalisation than by any recovery of the damaged liver. However, the lack of improvement in about 20% of patients, and the fairly wide scattering of individual data, suggest a minor LCAT production impairment in liver steatosis too. In cirrhosis, the major role seems to be played by a permanent decrease in LCAT production, as no significant rise in LCAT activity was observed after alcohol withdrawal. However the restored LCAT activity observed in some patients could be related to improvement in the metabolic disorder, thus confirming the effectiveness of this mechnism in cirrhosis too.(ABSTRACT TRUNCATED AT 250 WORDS)

Optimal strategy (staged or combined) for the treatment of patients with concurrent severe carotid and cardiac disease is still controversial. Moreover, carotid artery stenting (CAS), has become a valid alternative to carotid endarterectomy (CEA) and has been proposed for the treatment of cardiac patients. The authors report the preliminary results of a new therapeutic strategy consisting in combined CAS and cardiac surgery.An initial series of 22 patients underwent combined CAS and cardiac surgery in the same operating room and under general anesthesia. All filter-protected CAS procedures were performed under only heparin and aspirin. A cervical approach (3-cm cervicotomy) was used in patients with documented vessel tortuosity or severe aorto-iliac occlusive arteriopathy. In all the other cases a femoral access was used. A double antiplatelet regimen was initiated in the early postoperative period, once major bleedings were excluded.Among the 22 patients who underwent this combined procedure, no deaths, no myocardial infarctions and one controlateral stroke (overall complication rate: 4.5%) were observed. This stroke was observed after transcervical CAS, coronary artery bypass and mitral valve replacement. No major postoperative bleedings nor stent thrombosis were observed.Combined carotid stenting and cardiac surgery, performed in the same operating room under only heparin and aspirin, seems a safe and effective strategy for the treatment of patients with concomitant carotid and cardiac disease.