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In 1876, Bennett George Johns, a minister and chaplain at the school for the blind in St George's Field, published Blind People: Their Works and Ways; with Sketches of the Lives of Some Famous Blind Men. The book provided a window into the lives of the blind in Victorian England, with an emphasis on their education-or lack thereof. Johns was an observer of the blind and sympathetic to their plight. His depictions of schools were dispassionate, yet gently argued for improvement. Rather than rely on pity, he emphasized the benefits of institutionalized life and recounted the extraordinary achievements of four blind men. The creation of heroic historical figures had traditionally been employed to venerate political, military, or religious personages. Its use in shaping public perception of blindness was novel. This paper explores Johns's book as an early example of the innocent, myth-building of the blind and considers whether the process is always harmless., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The aim of this study was to describe how an early 20th-century American celebrity attempted to influence public perception of ophthalmic neonatorum., Methods: This study reviews the editorial written by Helen Keller in the 1909 Ladies' Home Journal and related historical documents about the prevention of blindness from neonatal conjunctivitis., Results: Although blind, deaf, and nulliparous, Helen Keller at the age of 29 sensed that the newborn children of many American women were being denied preventative treatment for ophthalmia neonatorum. In her editorial in the Ladies' Home Journal discussing the complications of venereal disease she urged women to become proactive in matters of personal and family health care., Conclusions: Helen Keller viewed blindness from ophthalmia neonatorum as a failure of the American health care system. Her solution was to impart women with enough knowledge to seek care from educated medical professionals. The observation that many women and their children were receiving substandard care reflected a fundamental problem with disparities in the delivery of perinatal health care. Her insights are as relevant today as they were in 1909., Competing Interests: The authors have no financial disclosures or conflicts of interest with the material presented in this manuscript., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Conjunctivitis, or inflammation of the mucosal covering the anterior third of sclera and inner eyelid, is a common clinical condition of varied causation. Most cases are self-limited due to infection or allergy and rarely necessitate biopsy. Inflammation of the conjunctiva, however, is one of the most common principal histopathologic diagnoses rendered when the tissue is biopsied. In the context of conjunctivitis, biopsy is usually performed when inflammation is chronic and recalcitrant to therapy, has clinically atypical features, or requires an etiologic diagnosis when one cannot be reached through other laboratory methods. The exclusion of ocular surface neoplasia in a chronically inflamed conjunctiva is a common justification for biopsy. When inflammation is the principal histopathology finding, it is desirable-whenever feasible-to establish the cause. This brief review provides a guide in how histologic findings of an inflamed conjunctiva can direct the clinical evaluation towards an etiologic diagnosis., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The 17th and 18th centuries witnessed an intellectual movement known as the Enlightenment that made possible future revolutions such as the scientific. No person better characterizes the Enlightenment than Voltaire (1696-1976) who, in his book Philosophical Letters published in 1734, venerated the liberalism of English institutions while criticizing the ancien régime of France. He was convinced that the personal freedom the English enjoyed was responsible for their country's success, pointing to inoculation for smallpox and advances in science as evidence. His choice of smallpox inoculation and science as exemplars of empiricism, which maintained that knowledge is obtained through sensory experience, is revealing as it pinpoints political flashpoints that persist to this day. This paper explores how inoculation and science were employed by Voltaire to advance his political idea of liberty.

Background: Few measures exist to assess the quality of care received by home care clients, especially at the end of life. Objective: This project examined the rates across a set of quality indicators (QIs) for seriously ill home care clients. Design: This was a cross-sectional descriptive analysis of secondary data collected using a standardized assessment tool, the Resident Assessment Instrument for Home Care (RAI-HC). Setting/Subjects: The sample included RAI-HC data for 66,787 unique clients collected between January 2006 and March 2018 in six provinces. Individuals were defined as being seriously ill if they experienced a high level of health instability, had a prognosis of less than six months, and/or had palliative care as a goal of care. Measurements: We compared individuals with cancer ( n  = 21,119) with those without cancer ( n  = 47,668) on demographic characteristics, health-related outcomes, and on 11 QIs. Results: Regardless of diagnosis, home care clients experienced high rates (i.e., poor performance) on several QIs, namely the prevalence of falls (cancer = 42.4%; noncancer = 55%), daily pain (cancer = 48.3%; noncancer = 43.2%), and hospital admissions (cancer = 48%; noncancer = 46.6%). The QI rates were significantly lower (i.e., better performance) for the cancer group for three out of the 11 QIs: falls (absolute standardized difference [SD] = 0.25), caregiver distress (SD = 0.28), and delirium (SD = 0.23). Conclusions: On several potential QIs, seriously ill home care clients experience high rates, pointing to potential areas for quality improvement across Canada.

After arriving at the University of Königsberg in 1849, Hermann von Helmholtz started investigating the trichromatic hypothesis of color perception proposed by Thomas Young. Four years later in 1853, he was invited to lecture to the German Society and used the opportunity to criticize harshly Johann Goethe's Theory of Color published in 1810. Offending a revered member of the German society was an odd method of introducing the study of color to a learned audience, but the content and tone of the lecture suggested Helmholtz was more concerned about dispelling misconceptions of experimental science than in imparting knowledge on the nature of color. By 1860, Helmholtz's color-mixing experiments provided further evidence for the trichromatic hypothesis. Goethe's ideas about color resonated intuitively with generations of artists, but the imperviousness of his theory to experimental testing set it apart from the arena of science., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Currently, there are no formalized measures for the quality of home based palliative care in Ontario. This study developed a set of potential quality indicators for seriously ill home care clients using a standardized assessment., Methods: Secondary analysis of Resident Assessment Instrument for Home Care data for Ontario completed between 2006 and 2013 was used to develop quality indicators (QIs) thought to be relevant to the needs of older (65+) seriously ill clients. QIs were developed through a review of the literature and consultation with subject matter experts in palliative care. Serious illness was defined as a prognosis of less than 6 months to live or the presence of severe health instability. The rates of the QIs were stratified across Ontario's geographic regions, and across four common life-limiting illnesses to observe variation., Results: Within the sample, 14,312 clients were considered to be seriously ill and were more likely to experience negative health outcomes such as cognitive performance (OR = 2.77; 95% CI: 2.66-2.89) and pain (OR = 1.59; 95% CI: 1.53-1.64). Twenty subject matter experts were consulted and a list of seven QIs was developed. Indicators with the highest overall rates were prevalence of falls (50%) prevalence of daily pain (47%), and prevalence of caregiver distress (42%). The range in QI rates was largest across regions for prevalence of caregiver distress (21.5%), the prevalence of falls (16.6%), and the prevalence of social isolation (13.7%). Those with some form of dementia were most likely to have a caregiver that was distressed (52.6%) or to experience a fall (53.3%)., Conclusion: Home care clients in Ontario who are seriously ill are experiencing high rates of negative health outcomes, many of which are amenable to change. The RAI-HC can be a useful tool in identifying these clients in order to better understand their needs and abilities. These results contribute significantly to the process of creating and validating a standardized set of QIs that can be generated by organizations using the RAI-HC as part of normal clinical practice.

In the early 1820s, a Yorkshire boarding school was devastated by an outbreak of blinding ophthalmia. The cause of the epidemic was-in all likelihood-trachoma, then known as Egyptian ophthalmia. The headmaster of the Yorkshire school, William Shaw, was sued for gross negligence by 2 families whose sons went blind during the outbreak. The epidemic and trial would play a role in creating one of the literature's most notorious fictional characters. Eighteen years after the trial, Charles Dickens modeled the vile schoolmaster Wackford Squeers in Nicholas Nickleby after Shaw, whose reputation and career would later be ruined by his thinly disguised portrayal in the novel. The original boarding school epidemic took place while London's first eye hospital was moving to Lower Moorfields, an institution that 17 years earlier was established primarily to cope with Egyptian ophthalmia. We explore trachoma's wide-ranging impact on pre-Victorian England, from inspiring an enduring literary villain to the creation of a renowned eye hospital., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Medical historians identify the mid-20th century as the time when the scientific and medical communities acknowledged the existence of autoimmune disease. Several conditions including sympathetic ophthalmia and endophthalmitis phacoanaphylactica, however, were proposed as autoimmune disorders much earlier. During the first half of the century, autoimmune disease was viewed as biologically implausible. Paul Ehrlich coined the term horror autotoxicus to emphasize that autoimmunity would contradict nature's aversion to self-injury. The discoveries of allergy and anaphylaxis were the first clues that the immune system was capable of self-harm. A major obstacle to comprehending the pathogenesis of autoimmunity was how the immune system distinguishes foreign from self, a process eventually understood in the context of immune tolerance. Investigators of sympathetic ophthalmia and endophthalmitis phacoanaphylactica were positioned to invalidate horror autotoxicus but lacked sufficiently convincing experimental and clinical evidence to accomplish the task. Seminal studies of chronic thyroiditis and a series of clinical laboratory breakthroughs led to the general acceptance of autoimmune disease in the 1950s. The travails encountered by ophthalmic investigators offer insights into the how medical ideas take shape. We review the contributions of ocular immunology to the conceptual development of autoimmune disease and explore the reasons why the concept caught on slowly., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Herpes simplex virus 1 (HSV-1) establishes life-long latent infection within sensory neurons, during which viral lytic gene expression is silenced. The only highly expressed viral gene product during latent infection is the latency-associated transcript (LAT), a non-protein coding RNA that has been strongly implicated in the epigenetic regulation of HSV-1 gene expression. We have investigated LAT-mediated control of latent gene expression using chromatin immunoprecipitation analyses and LAT-negative viruses engineered to express firefly luciferase or β-galactosidase from a heterologous lytic promoter. Whilst we were unable to determine a significant effect of LAT expression upon heterochromatin enrichment on latent HSV-1 genomes, we show that reporter gene expression from latent HSV-1 genomes occurs at a greater frequency in the absence of LAT. Furthermore, using luciferase reporter viruses we have observed that HSV-1 gene expression decreases during long-term latent infection, with a most marked effect during LAT-negative virus infection. Finally, using a fluorescent mouse model of infection to isolate and culture single latently infected neurons, we also show that reactivation occurs at a greater frequency from cultures harbouring LAT-negative HSV-1. Together, our data suggest that the HSV-1 LAT RNA represses HSV-1 gene expression in small populations of neurons within the mouse TG, a phenomenon that directly impacts upon the frequency of reactivation and the maintenance of the transcriptionally active latent reservoir.

Background: Systemic cancer therapies cause a variety of ophthalmic complications. Mitigating harmful adverse events involves screening patients at risk for ocular injury and vision loss., Methods: A review of the relevant literature on the ophthalmic complications of cancer therapy was used to formulate an approach to screening patients for serious complications presenting at a nonophthalmic specialty center., Results: Rarely, ocular complications of cancer therapy can occur. Establishing a causal association for any given agent is complicated because many treatment-related adverse events result in symptoms and ocular findings indistinguishable from primary eye disorders., Conclusions: Recognizing potentially serious ocular complications of cancer therapy before they result in irreversible injury starts with taking a relevant clinical history and performing a basic eye examination, including assessments of visual acuity and fields. Given the wide range of treatment-related adverse events and the challenges of diagnosis, the screening process plays an important role in expediting referral to an ophthalmologic specialist.

In the seven decades since Schrödinger's book was published, it has gone through stages of differing appraisal, starting with guarded approbation in the 1940s. When several luminaries in molecular biology described the work as influencing their careers, the book's renown increased. In What Is Life?, Schrödinger examined genetics from the perspective of a theoretical physicist, and conjured up ideas that dilettantes admired and experts slighted. Schrödinger sowed his most important ideas in terms of metaphors, allowing readers considerable latitude for interpretation. Some found nothing worthwhile in the book, only chemical naivete and ignorance of work that had already been done. Others found deep inspiration and a desire to understand biological reproduction, even if it required new paradigms of physical science. What Is Life?--like the ancient parable of the blind men and an elephant--is an example of the ineffable nature of truth, pitting subjective experience against the totality of the reality. The legacy of What Is Life? may ultimately be respect for different opinions.

Factors influencing T-cell responses are important for vaccine development but are incompletely understood. Here, vaccinia virus (VACV) protein N1 is shown to impair the development of both effector and memory CD8(+) T cells and this correlates with its inhibition of nuclear factor-κB (NF-κB) activation. Infection with VACVs that either have the N1L gene deleted (vΔN1) or contain a I6E mutation (vN1.I6E) that abrogates its inhibition of NF-κB resulted in increased central and memory CD8(+) T-cell populations, increased CD8(+) T-cell cytotoxicity and lower virus titres after challenge. Furthermore, CD8(+) memory T-cell function was increased following infection with vN1.I6E, with more interferon-γ production and greater protection against VACV infection following passive transfer to naive mice, compared with CD8(+) T cells from mice infected with wild-type virus (vN1.WT). This demonstrates the importance of NF-κB activation within infected cells for long-term CD8(+) T-cell memory and vaccine efficacy. Further, it provides a rationale for deleting N1 from VACV vectors to enhance CD8(+) T-cell immunogenicity, while simultaneously reducing virulence to improve vaccine safety., (© 2014 The Authors. Immunology Published by John Wiley & Sons Ltd.)

Purpose: To critique Rudolf Virchow's medical school dissertation on rheumatism and the cornea and to determine whether it might have anticipated his remarkable career in medicine., Methods: Review of the English translation of Rudolf Virchow's de Rheumate Praesertim Corneae written in 1843., Results: The dissertation was more than 7000 words long. Virchow considered rheumatism as an irritant disorder not induced by acid as traditionally thought but by albumin. He concluded that inflammation was secondary to a primary irritant and that the "seat" of rheumatism was "gelatinous" (connective) tissues, which included the cornea. He divided kerato-rheumatism into different varieties. The prognosis of keratitis was variable, and would eventually lapse into "scrofulosis, syphilis, or arthritis of the cornea.", Conclusions: Virchow's dissertation characterizes rheumatism in terms of chemical and tissue interactions that make little sense in the context of today's knowledge of rheumatic disease and keratitis. Ironically, many of these concepts were made obsolete by the cellular model of disease that Virchow championed. Virchow decided to pursue the study of rheumatism through the cornea because he thought that the cornea was an ideal tissue to study disease. This discernment was passed on to his students whose seminal contributions to general pathology were based on research with the cornea. It is debatable whether Virchow's insight into the importance of the cornea in biomedical research at such an early stage of his career could have predicted his monumental contributions to medicine.

Uveitis, or inflammation of the uveal tract (i.e., iris, ciliary body, and choroid), results from a heterogeneous collection of disorders of varying etiologies and pathogenic mechanisms. Uveitis is caused by a systemic disease in 30% to 45% of patients. Primary care physicians may be asked to evaluate patients with uveitis when an underlying systemic diagnosis is suspected but not apparent from eye examination or history. If the history, physical examination, and basic laboratory studies do not suggest an underlying cause, serologic tests for syphilis and chest radiography for sarcoidosis and tuberculosis are recommended. Typing for human leukocyte antigen-B27 is appropriate for patients with recurrent anterior uveitis. Because the prevalence of many rheumatologic and infectious diseases is low among persons with uveitis, Lyme serology, antinuclear antibody tests, serum angiotensin-converting enzyme tests, serum lysozyme tests, and tuberculin skin tests can result in false-positive results and are not routinely recommended. Drug-induced uveitis is rare and can occur from days to months after the time of initial exposure. Primary ocular lymphoma should be considered in persons older than 50 years with persistent intermediate or posterior uveitis that does not respond to anti-inflammatory therapy.

An outbreak of cataracts in 1935 caused by dinitrophenol (DNP), the active ingredient of popular diet pills, highlighted the inability of the U.S. Food and Drug Administration (FDA) to prevent harmful drugs from entering the marketplace. Just two years earlier, the FDA used horrific images of ocular surface injury caused by cosmetics at the World's Fair in Chicago to garner public support for legislative reform. The FDA had to walk a fine line between a public awareness campaign and lobbying Congress while lawmakers debated the need for consumer protection. The cataract outbreak of 1935 was conspicuous in the medical literature during the height of New Deal legislation, but questions persist as to how much it affected passage of the proposed Food, Drug, and Cosmetic Act (of 1938). The legislation languished in committee for years. The cataract outbreak probably had little impact on the eventual outcome, but medical opinion concerning the safety of DNP may have contributed to the voluntary withdrawal of the diet drug from the market. We review the DNP cataract outbreak and examine it in context of the challenges facing regulatory reform at that time., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The diagnosis of feigned vision loss in adults taxes the doctor-patient relationship because the relationship should be based on trust, honesty, and the mutual desire to improve the medical condition. Even under ideal circumstances, physicians rarely have a complete understanding of the factors that lead patients to simulate disease they do not have. We describe the historical figure of John Howard Griffin (1920-1980) who likely perpetuated feigned vision loss for a decade. His writings provide a unique perspective on motivation (or inspiration) behind factitious disease.

Several months after anonymously publishing an essay in 1749 with the title "Letter on the Blind for the Use of Those Who Can See," the chief editor of the French Encyclopédie was arrested and taken to the prison fortress of Vincennes just east of Paris, France. The correctly assumed author, Denis Diderot, was 35 years old and had not yet left his imprint on the Age of Enlightenment. His letter, which recounted the life of Nicolas Saunderson, a blind mathematician, was intended to advance secular empiricism and disparage the religiously tinged rationalism put forward by Rene Descartes. The letter's discussion of sensory perception in men born blind dismissed the supposed primacy of visual imagery in abstract thinking. The essay did little to resolve any philosophical controversy, but it marked a turning point in Western attitudes toward visual disability.

Background: Pseudoexfoliation is a systemic disorder characterized by the deposition of extracellular matrix material. The microfibrillar material that gives rise to the condition is visible clinically in the anterior segment of the eye, and is also found in other tissues, including blood vessels, skin, gallbladder, kidneys, lungs, and heart., Aims: The present study aims to determine whether ocular pseudoexfoliation is associated with selected cardiovascular diseases., Materials and Methods: A cross-section comparison study was conducted with the help of the Veterans Health Administration databases, using the International Classification of Diseases, Ninth revision, Clinical Modification for pseudoexfoliation of lens capsule and pseudoexfoliation glaucoma. Selected cardiovascular diseases and risk factors for cardiovascular disease were identified using the appropriate medical codes. Patients with primary open-angle glaucoma, chronic sinusitis, and benign prostatic hyperplasia served as the comparison groups. A logistic regression model was used to control for age, gender, race, and major cardiovascular risk factors., Results: There were 6,046 case patients with pseudoexfoliation; approximately half were diagnosed with pseudoexfoliation glaucoma. Various stages of ischemic heart disease, cardiomyopathy, and aortic aneurysm were significantly associated with ocular pseudoexfoliation, after controlling for age, gender, race, and major cardiovascular risk factors. Associations, in general, were less demonstrable relative to the primary open-angle glaucoma comparison group., Conclusion: Associations of ocular pseudoexfoliation with cardiovascular diseases were generally fewer and less pronounced when compared to patients with primary open-angle glaucoma. These results add to the results of earlier studies, which suggest that open-angle glaucoma itself might be a risk factor for certain cardiovascular disorders.

Samuel Johnson, the acclaimed author of the Dictionary of the English Language, survived childhood scrofula with impaired sight and hearing. The cause of his scrofula has been attributed to bovine tuberculosis, but mycobacterial infection does not satisfactorily account for the peculiar features of Johnson's eye disorder or his hearing loss. The subject of numerous biographies, Johnson may have the most scrutinized medical history of all time. Medical detectives, hampered by the vagueness of 18(th)-century diagnosis, suspect that phlyctenular eye disease related to tuberculosis was the reason for his visual impairment. Pediatric brucellosis can also explain childhood scrofula associated with visual and auditory disabilities, but it may be difficult to reconcile any single diagnosis given the uncertainties surrounding Johnson's medical and ocular histories., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To test the hypothesis that cocaine use (abuse and/or dependency) is associated with open-angle glaucoma., Methods: A case-control study. Potential case patients were identified from the Veterans Health Administration national clinical database using International Classification of Disease, Version 9, Clinical Modification for open-angle glaucoma for fiscal year 2009. Inclusion criteria included consecutive prescriptions for 1 or more topical antiglaucoma medications. Cocaine exposure was identified through International Classification of Disease, Version 9, Clinical Modification codes. The odds of cocaine exposure were compared with the overall outpatient population of national Veterans Health Administration beneficiaries and adjusted for age and other illicit drug use. A nested case-control study was conducted to examine the confounding influence of race., Results: Age-adjusted odds ratios of cocaine exposure among patients with glaucoma were statistically significant for both men [3.52 (95% confidence interval, CI: 3.21-3.86)] and women [1.87 (95% CI: 1.79-1.96)], and did not change significantly when analyzed according to drug-dependency status. Subset analysis adjusted for age, other illicit drugs, and race remained significant for men [1.45 (95% CI: 1.27-1.66)], but not women. Persons with substance use disorder and glaucoma were nearly 18 years younger than glaucoma patients without a drug exposure history., Conclusions: This pilot study suggests the use of cocaine and possibly other illicit drugs are predictive of glaucoma. Should the association of substance use disorder (cocaine or cocaine/poly-drug abuse) and open-angle glaucoma be verified, it represents a potentially modifiable risk factor for vision loss.

Generations of disabled persons were inspired by the miraculous recovery Charles Fletcher Lummis made following a series of devastating strokes that began at the age of 28. The famed author, editor, and social activist was struck by misfortune again at 51 when he went bilaterally blind. At the height of his career, Lummis never let the loss of vision interfere with his many professional responsibilities or his personal life. The cause of Lummis's stroke and blindness has been the subject of speculation for nearly a century and involves one of the most sensitive and perplexing diagnoses in medicine.

Symptomatic PVD is a common age-related problem that in some patients is associated with retinal tear and retinal detachment. Thorough ocular examination of patients with unilateral floaters and photopsias is needed to identify those at greatest risk for vision loss. Patients without retinal pathologic findings on initial examination need to be given careful instructions on what to expect and do should symptoms of retinal tear or detachment occur.

The reliability of clinical methods is often taken for granted. There is considerable evidence, however, that variability of clinical measurements, interpretations, and judgements are greater than commonly thought. Inconsistency of clinical methods has profound and widespread implications in clinical practice. The inferential capacity of measurements depends on accuracy and reproducibility. Appropriate medical decisions cannot be reached without accurate and reliable data. This review will examine the conceptual relationship of reliability, accuracy, and validity. The role of observer reliability in ophthalmic test measurements and interpretations will be addressed in the context of three case reports.

Objectives: To compare the inflammatory reaction associated with the insertion of silicone and polypropylene endplates and endplates made of a new biocompatible polymer, Vivathane, in the rabbit subconjunctival space., Methods: Similar-sized endplates made of 3 different biomaterials were sutured to the sclera in the superotemporal quadrant of the rabbit eye. Thirty eyes of 15 albino New Zealand rabbits were randomly assigned to the 3 groups. Conjunctival vascular hyperemia was graded in a masked fashion among groups. At the end of 3 weeks, the enucleated eyes were examined histologically and using scanning electron microscopy., Results: Polypropylene and Vivathane were associated with significantly more inflammation in clinical observations and based on histological grading. Silicone was associated with the least amount of inflammation. Three polypropylene and 1 Vivathane plate were extruded between the second and third week., Conclusions: Silicone is the most inert of the 3 materials tested. Inflammation associated with biomaterials may contribute to the failure of the glaucoma drainage devices., Clinical Relevance: Bleb inflammation may be related to the biomaterial being used as the endplate. Endplates should be handled carefully during surgery to avoid creating rough spots.

Purpose: To describe four patients who developed cystoid macular edema shortly after onset of treatment with latanoprost., Method: Retrospective review of medical records of patients with open-angle glaucoma who developed cystoid macular edema shortly after starting latanoprost., Results: The use of topical latanoprost was temporally related to the development of cystoid macular edema in four patients (six eyes; two aphakic eyes and four pseudophakic eyes). Cystoid macular edema resolved in all patients after latanoprost was discontinued., Conclusions: Cystoid macular edema is a potential complication of latanoprost therapy. Further observations are needed to determine if the risk of cystoid macular edema is limited to or greatest in patients who are pseudophakic or aphakic.

Clinical manifestations of Wegener's granulomatosis are nonspecific and indistinguishable from a variety of neoplastic, infectious, and inflammatory diseases. Ophthalmic disease is the presenting feature in nearly one sixth of patients with Wegener's granulomatosis and will ultimately develop in a majority. The discovery of antineutrophil cytoplasmic antibodies, particularly antiproteinase-3, has changed the clinical approach to evaluating patients suspected of having Wegener's granulomatosis. These antibodies are distinguished from other related autoantibodies because they produce a coarse granular pattern of cytoplasmic staining on indirect immunofluorescence with ethanol-fixed neutrophils. Treatment of Wegener's granulomatosis with oral cyclophosphamide and corticosteroids has decreased morbidity and improved survival, but side effects from long-term immunosuppressive therapy are common and sometimes serious. The effectiveness of trimethoprim-sulfamethoxazole in decreasing the number and severity of recurrences of Wegener's granulomatosis is being investigated. It remains to be determined if wide use of trimethoprim-sulfamethoxazole in limited Wegener's granulomatosis could further improve the quality of life for some patients.

A patient with acute carbon monoxide poisoning due to leakage of gas from the exhaust system in his automobile noted edema and blister formation over large areas of the skin of one half of his body. Rhabdomyolysis, acute but transient renal insufficiency, and hemolytic anemia developed subsequently.

The diagnosis of sarcoidosis is best established when there is evidence of granulomatous involvement in two or more organs. Three patients with unusual cutaneous manifestations of sarcoidosis, including palmar and follicular lesions, nonscarring alopecia, and widespread plaque or erythrodermic sarcoidosis, are reported. In all three patients the skin biopsy was important in establishing the diagnosis.

Microfilariae of O. volvulus were recovered from the urine of 11% of the residents of a village in the Republic of Chad where onchocerciasis was holoendemic. A follow-up study of the same population 3 years after the original investigation revealed that microfilaruria was still present and that living microfilariae of O. volvulus could be recovered from small urine samples obtained by high catherization of the ureters. Radiological changes consistent with chronic pyelitis were found in 4 out of 14 persons with microfilaruria who were examined by retrograde pyelography. The recovery of microfilariae in the urine was associated with the intensity of the infection, as determined by counts of microfilariae in skin snips and the number of onchocercomata. A systematic comparison for differences between onchocerciasis patients with and without microfilaruria revealed that the microfilaruria patients had a low weight: height ratio, deficient antibody responses in indirect haemagglutination tests with O. volvulus antigen, elevated serum aminotransferase levels, and reduced systolic blood pressure.