Amantadine and Modafinil as Neurostimulants Following Acute Stroke: A Retrospective Study of Intensive Care Unit Patients.

BACKGROUND/OBJECTIVE: Neurostimulants may improve or accelerate cognitive and functional recovery after intracerebral hemorrhage (ICH), ischemic stroke (IS), or subarachnoid hemorrhage (SAH), but few studies have described their safety and effectiveness in the intensive care unit (ICU). The objective of this study was to describe amantadine and modafinil administration practices during acute stroke care starting in the ICU and to evaluate safety and effectiveness. METHODS: Consecutive adult ICU patients treated with amantadine and/or modafinil following acute non-traumatic IS, ICH, or SAH were evaluated. Neurostimulant administration data were extracted from the electronic medication administration record, including medication (amantadine, modafinil, or both), starting dose, time from stroke to initiation, and whether the neurostimulant was continued at hospital discharge. Patients were considered responders if they met two of three criteria within 9 days of neurostimulant initiation: increase in Glasgow coma scale (GCS) score ≥ 3 points from pre-treatment baseline, improved wakefulness or participation documented in caregiver notes, or clinical improvement documented in physical or occupational therapy notes. Potential confounders of the effectiveness assessment and adverse drug effects were also recorded. RESULTS: A total of 87 patients were evaluable during the 3.7-year study period, including 41 (47%) with ICH, 29 (33%) with IS, and 17 (20%) with SAH. The initial neurostimulant administered was amantadine in 71 (82%) patients, modafinil in 13 (15%), or both in 3 (3%) patients. Neurostimulants were initiated a median of 7 (4.25, 12.75) days post-stroke (range 1-27 days) for somnolence (77%), not following commands (32%), lack of eye opening (28%), or low GCS (17%). The most common starting dose was 100 mg twice daily for both amantadine (86%) and modafinil (54%). Of the 79 patients included in the effectiveness evaluation, 42 (53%) were considered responders, including 34/62 (55%) receiving amantadine monotherapy and 8/24 (33%) receiving both amantadine and modafinil at the time they met the definition of a responder. No patient receiving modafinil monotherapy was considered a responder. The median time from initiation to response was 3 (2, 5) days. Responders were more frequently discharged home or to acute rehabilitation compared to non-responders (90% vs 62%, p = 0.006). Among survivors, 63/72 (88%) were prescribed a neurostimulant at hospital discharge. The most common potential adverse drug effect was sleep disruption (16%). CONCLUSIONS: Neurostimulant administration during acute stroke care may improve wakefulness. Future controlled studies with a neurostimulant administration protocol, prospective evaluation, and discretely defined response and safety criteria are needed to confirm these encouraging findings.

Incorporating Carbohydrates into Laboratory Curricula.

As an important but underappreciated field, carbohydrate chemistry is a critical topic for undergraduate students to learn. With applications to nutrition, food science, and diabetes, carbohydrates provide real-world relevance to students. This review summarizes the literature of undergraduate laboratory experiments which use carbohydrates since the year 2000. Experiments explore important chemical concepts such as synthesis, kinetics, analysis, and computational chemistry. Experiments designed for general chemistry, organic chemistry, biochemistry, and analytical chemistry at a variety of skill levels are presented.

Wernicke encephalopathy associated with hyperemesis gravidarum.

Emergency physicians frequently treat hyperemesis gravidarum and should be aware of possible complications. Wernicke encephalopathy secondary to thiamine deficiency should be considered in the differential diagnosis of acute encephalopathy in pregnant women. A seventeen-week pregnant 27-year-old woman presented to the Emergency Department with nausea, emesis, and right upper quadrant abdominal pain. Ultrasound diagnosed gallbladder sludge. Surgical consultant offered cholecystectomy versus expectant management. She improved with IV hydration, ondansetron, and was discharged on hospital day 3 with a diagnosis of hyperemesis gravidarum and gallbladder sludge. Three days later she presented with continued emesis and altered mental status. She and family members denied alcohol or illicit drug use. Vital signs were pulse 99/min, blood pressure 115/70, temperature 36.4 °C, respiratory rate 18, and oxygen saturation 99%. Neurological examination was delirium, variable mentation, and inability to follow commands. She had internuclear opthalmoplegia with bilateral nystagmus. CT scan of brain was negative. MRI found abnormal T2-weighted signal in the central pons and medial thalami. Radiographic differential included central pontine myelinolysis, dysmyelinating conditions from malnutrition, toxic encephalopathy, and Wernicke encephalopathy. Thiamine level was below the limits of detection. Alcohol and urine drug screen were negative. Diagnosis was thiamine deficiency secondary to hyperemesis gravidarum with Wernicke encephalopathy. Emergency physicians frequently treat hyperemesis gravidarum. Nutritional status should be evaluated in patients who are unable to take neonatal vitamins. Awareness should exist of possible complications, including Wernicke encephalopathy secondary to thiamine deficiency.

Amantadine and Modafinil as Neurostimulants During Post-stroke Care: A Systematic Review.

Amantadine and modafinil are neurostimulants that may improve cognitive and functional recovery post-stroke, but the existing study results vary, and no comprehensive review has been published. This systematic review describes amantadine and modafinil administration practices post-stroke, evaluates timing and impact on clinical effectiveness measures, and identifies the incidence of potential adverse drug effects. A librarian-assisted search of the MEDLINE (PubMed) and EMBASE databases identified all English-language publications with "amantadine" or "modafinil" in the title or abstract from inception through February 1, 2020. Publications meeting predefined Patient, Intervention, Comparator, Outcome (PICO) criteria were included: Patients (≥ 18 years of age post-stroke); Intervention (amantadine or modafinil administration); Comparison (pretreatment baseline or control group); Outcomes (cognitive or functional outcome). Amantadine and modafinil administration practices, cognitive and functional outcomes, and incidence of potential adverse drug effects were collected following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidance. Quantitative analyses were not performed due to heterogeneity in the clinical effectiveness measures; descriptive data are presented as number (percent) or median (interquartile range). Of 12,620 publications initially identified, 10 amantadine publications (n = 121 patients) and 12 modafinil publications (n = 120 patients) were included. Amantadine was initiated 39 (16, 385) days post-stroke, with most common initial doses of 100 mg once or twice daily (range 100-200 mg/day), and final daily dose of 200 (188, 200) mg/day. Modafinil was initiated 170 (17, 496) days post-stroke, with initial and final daily doses of 100 (100, 350) mg/day and 200 (100, 350) mg/day, respectively. The most common indication was consciousness disorders for amantadine (n = 3/10 publications; 30%) and fatigue for modafinil (n = 5/12; 42%). Forty unique clinical effectiveness measures (1.8 per study) with 141 domains (6.4 per study) were described across all studies. A positive response in at least one clinical effectiveness measure was reported in 70% of amantadine publications and 83% of modafinil publications. Only one publication each for amantadine (10%; n = 5 patients) and modafinil (8%; n = 21 patients) studied acutely hospitalized or ICU patients; both were randomized studies showing improvements in neurocognitive function for amantadine and fatigue for modafinil. Potential adverse drug effects were reported in approximately 50% of publications, most commonly visual hallucinations with amantadine (2% of patients) and dizziness (5% of patients) and dry eyes or mouth (5% of patients). Amantadine and modafinil may improve cognitive and functional recovery post-stroke, but higher-quality data are needed to confirm this conclusion, especially in the acute care setting.

Retrospective chart review of substance abuse in patients with psychiatric emergencies in an emerging urban county.

Objectives: Substance abuse is common in patients with psychiatric emergencies. To further understand the connection between substance abuse and psychiatric disorders, a retrospective chart review was done that included positive drug screens among patients with psychiatric emergencies and to determine whether there was an association between substances used and the psychiatric diagnosis. Methods: A retrospective chart review of patients seen in an emergency department with psychiatric emergencies was conducted. The review comprised 1000 charts with diagnoses of anxiety, depression, schizophrenia, attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, alcohol abuse, or schizoaffective disorder. Data collected included patient demographics, tobacco abuse, chief complaint, arrival mode, voluntary versus involuntary status, suicide attempt on presentation, psychiatric diagnoses, urine drug screen, and ethanol results. Chi-square statistical analysis was conducted to examine the relationship between substances of abuse and psychiatric diagnoses. Results: Approximately 58% of patients with a history of psychiatric illness had a positive urine drug screen. Of 245 patients with schizoaffective disorder, 69 (28%) were positive for tetrahydrocannabinol (THC) and 48 (20%) were positive for cocaine. Of 225 patients with depression, 59 (29%) were positive for THC and 33 (15%) were positive for cocaine. Cannabis was the most commonly reported substance used among patients with depression, schizophrenia, anxiety, schizoaffective disorder, and bipolar disorder, and ethanol was most common in patients with ADHD. No significant correlations were found between psychiatric diagnosis and positive drug screens. A statistically significant secondary end point was found that White people using cannabinoids were more likely to attempt suicide than were African American people (P = 0.02). Conclusions: Positive drug screens were common among patients presenting to an ED with psychiatric emergencies. Cannabis was the most commonly reported substance used among patients independent of diagnosis. Ethanol was the most common in patients with ADHD. Urine drug screens are unlikely to provide insights into relationships between specific substance use and psychiatric emergencies.

Trending of a falsely elevated serum creatinine after a pediatric nitromethane ingestion: A case report.

Introduction: Nitromethane is a primary nitroalkane used as a solvent and a fuel that may be toxic by ingestion, inhalation, or contact. Its presence can be detected in serum of exposed persons, but levels are not readily available to guide patient care. Nitromethane has been shown to falsely elevate serum creatinine when clinical laboratories use Jaffe assays to measure creatinine; enzymatic assays are not affected. Ex vivo experiments have demonstrated a linear relationship between serum nitromethane and the elevation in Jaffe assay creatinine. This case report demonstrates an elevation of creatinine measured by Jaffe assay with normal creatinine measurement by enzymatic assay after exposure to nitromethane. Case report: A 21-month-old girl ingested an unmeasured quantity of a hobby fuel, a fuel containing methanol, nitromethane (20%), and lubricants used in miniature internal combustion engines, such as remote-controlled cars. She was initially evaluated at a community hospital, treated empirically for methanol toxicity with fomepizole and folic acid, and transferred to a university hospital for further management. By 19 hours after ingestion, methanol was below detection, but a serum creatinine of 2.63 mg/dl raised concern for kidney injury. Toxicology consultation recognized that the creatinine had been measured using a Jaffe assay and recommended a repeat creatinine using an enzymatic assay, which was within normal limits. The patient remained an inpatient for further evaluation, which permitted trending of her Jaffe assay creatinine over a 3-day period. The Jaffe assay creatinine demonstrated a gradual decline; repeat enzymatic assay creatinine remained within normal limits. Discussion: The decline in this pediatric patient's Jaffe assay creatinine is consistent with first-order clearance of nitromethane, which has been previously described in adult exposures. This case demonstrates how Jaffe assay-derived serum creatinine may be useful in the pediatric population to establish, quantify, and trend nitromethane exposure with essential concurrent use of an enzymatic assay to determine actual creatinine.

Failure of Computed Tomography (CT) in Detecting an Aspirin Pharmacobezoar: A Case Report.

BACKGROUND Prior studies suggest CT can identify bezoars under certain circumstances. Endoscopy provides diagnostic and therapeutic benefit in the setting of suspected aspirin bezoar. Does the absence of findings on CT scan exclude the presence of an aspirin bezoar? CASE REPORT A 64-year-old woman called the police and stated she ingested a bottle of aspirin to harm herself. Upon arrival to the Emergency Department, she was tachypneic with a GCS of 15. Initial laboratory results were: salicylate level of 1143 mcg/mL, respiratory alkalosis, bicarbonate of 9 meq/L, anion gap of 23, and normal renal function. Initial therapeutic intervention included infusions of glucose and bicarbonate, multiple doses of activated charcoal, intubation, and emergent hemodialysis. After hemodialysis, the salicylate level rebounded, and a Gastroenterology (GI) consultation was requested to rule out bezoar. On day 2, GI requested an abdominal CT scan with Gastrografin in place of endoscopy due to hemodynamic instability. A CT scan was negative for bezoar. After multiple hemodialysis sessions and whole-bowel irrigation with rebounding salicylate levels, GI was consulted again for reevaluation for endoscopy. On day 5, an endoscopy discovered a concretion containing pill fragments. Another endoscopy performed on day 7 removed further fragments. Salicylate levels began to consistently decline. Unfortunately, the patient's neurologic status did not improve, and on day 11 she was switched to palliative care and died. CONCLUSIONS Endoscopy with direct visualization is diagnostic and therapeutic in the setting of a possible bezoar. The absence of pharmacobezoar on imaging should not delay endoscopy in a clinical setting suggesting bezoar.

First Aid and Pre-Hospital Management of Venomous Snakebites.

BACKGROUND: Antivenom is the definitive treatment for venomous snakebites, but is expensive and not available in many rural and poorly developed regions. Timely transportation to facilities that stock and administer antivenom may not be available in rural areas with poorly developed emergency medical services. These factors have led to consideration of measures to delay onset of toxicity or alternatives to antivenom therapy. METHODS: PubMed searches were conducted for articles on snakebite treatment, or that contained first aid, emergency medical services, tourniquets, pressure immobilization bandages, suction devices, and lymphatic flow inhibitors. RESULTS: The reviewed articles describe how venoms spread after a venomous snakebite on an extremity, list the proposed first aid measures for delaying the spread of venoms, and evaluate the scientific studies that support or refute methods of snakebite first aid. The recommendations for field treatment of venomous snakebites will be discussed. CONCLUSIONS: The evidence suggests that pressure immobilization bandages and related strategies are the best interventions to delay onset of systemic toxicity from venomous snakebites but may increase local toxicity for venoms that destroy tissue at the site of the bite, so their use should be individualized to the circumstances and nature of the venom.

Enzyme-linked immunosorbent assays for coproantigen detection of Ancylostoma caninum and Toxocara canis in dogs and Toxocara cati in cats.

We report the development and field validation of 2 ELISAs for the detection of Ancylostoma caninum or Toxocara canis coproantigens in the feces of dogs with experimental and natural infections, and evidence of cross-reactivity with respective feline counterparts. A. caninum-specific coproantigens were detected in feces of experimentally infected dogs starting at 9 d post-infection (dpi), whereas eggs were not seen until 23 dpi. T. canis-specific coproantigens were detected in 3 of 5 experimentally infected dogs by 31 dpi, and 4 of the 5 animals by 38 dpi. T. canis eggs were seen in feces of 4 of the 5 animals by 38 dpi. One dog had delayed coproantigen detection and low egg output. Additionally, 817 canine and 183 feline fecal samples from naturally infected animals tested by flotation were subjected to coproantigen ELISA testing. Of these 1,000 canine and feline samples, 13 and 23 samples, respectively, were positive for "hookworm" or "roundworm" eggs; 19 and 26 samples were ELISA positive, respectively. The T. canis ELISA detected T. cati coproantigen in cat fecal samples. Discrepant ELISA and flotation results were obtained for 16 hookworm- and 13 roundworm-positive samples. Re-examination of the egg-positive, ELISA-negative samples indicated several instances of possible misidentification or coprophagy, whereas detection of antigen in samples without egg observations is likely a reflection of true infection status with egg shedding below detection levels. There is good indication, based on accumulated field data, that these antigen tests also detect other hookworm and ascarid species.

The toxicity of picaridin containing insect repellent reported to the National Poison Data System.

CONTEXT: While low toxicity is reported, there are sparse data on the safety of acute picaridin (icaridin) exposures in humans. OBJECTIVE: The purpose of this study was to review National Poison Data System (NPDS) data regarding ingestion of insect repellents containing picaridin and compare those to insect repellents containing DEET and other insect repellents not containing DEET. METHODS: NPDS was queried for single agent human insect repellent ingestions reported between 1 January 2000 and 31 May 2015 using the American Association of Poison Control Center generic categories 201048 (Insect Repellents with DEET) and 201049 (Insect Repellents without DEET). Picaridin-containing product exposures were assessed using Poisindex(®) product ID 6744589. Insect repellents of unknown type were not included. RESULTS: 68,429 exposures occurred; 24% were non-DEET-containing products, of which 2% were picaridin-containing products. Among picaridin exposures, 92.9% were managed outside of a health-care facility; there were no reported cases of major effect or death, and only one case of moderate effect. Primary symptoms across all insect repellent exposures included ocular irritation/pain, vomiting, red eye/conjunctivitis, and oral irritation. Treatment primarily included dilution/irrigation/wash. CONCLUSION: Unintentional ingestion of picaridin-containing and other insect repellents was associated only with minor toxicity and was generally managed outside of a health-care facility.

The US twin study of age-related macular degeneration: relative roles of genetic and environmental influences.

CONTEXT: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among older individuals in many parts of the world. The relative importance of genes and environment in the etiology of this major public health problem is not well understood. OBJECTIVE: To investigate the impact of genetic and environmental factors. PARTICIPANTS: Living twins in the National Academy of Sciences-National Research Council World War II Veteran Twin Registry born between 1917 and 1927. METHODS: Twins were surveyed for the known presence of macular degeneration. Enrolled twins underwent a standardized examination and fundus photography. Age-related macular degeneration evaluation was completed for 840 elderly male twins, 210 monozygotic and 181 dizygotic complete twin pairs, both concordant and discordant for presence or absence of AMD, and 58 singletons. A bivariate twin model incorporating initial screening ascertainment and age effects was employed to partition variation in liability to AMD and signs of maculopathy into additive genetic, common environment, and unique environment components. MAIN OUTCOME MEASURE: Heritability of AMD grade and signs of maculopathy based on clinical examination and fundus photographs. RESULTS: Of the 840 twins, 331 had no signs of maculopathy and 241 had early signs, while 162 had intermediate AMD and 106 had advanced AMD. Heritability (additive genetic) estimates were significant for overall AMD grade (0.46) and for intermediate (0.67) and advanced (0.71) AMD. Significant unique environmental proportions of variance were also observed for these AMD variables (0.37, 0.19, and 0.24, respectively). Shared or common environmental contributions were not significant (0.05-0.17). For specific macular drusen and retinal pigment epithelial characteristics, significant genetic (0.26-0.71) and unique environmental (0.28-0.64) proportions of variance were detected. CONCLUSIONS: Genetic factors play a substantial role in the etiology of AMD and associated macular characteristics, explaining 46% to 71% of the variation in the overall severity of the disease. Environmental factors unique to each twin also contribute to the occurrence of this disease. This quantification of relative genetic and environmental contributions to the development of AMD should guide future research on this important cause of blindness.

Efficacy of Trypsin in Treating Coral Snake Envenomation in the Porcine Model.

Antivenom is the definitive treatment for venomous snakebites. Alternative treatments warrant investigation because antivenom is sometimes unavailable, expensive, and can have deleterious side effects. This study assesses the efficacy of trypsin to treat coral snake envenomation in an in vivo porcine model. A randomized, blinded study was conducted. Subjects were 13 pigs injected subcutaneously with 1 mL of eastern coral snake venom (10 mg/mL) in the right distal hind limb. After 1 min, subjects were randomized to have the envenomation site injected with either 1 mL of saline or 1 mL of trypsin (100 mg/mL) by a blinded investigator. Clinical endpoint was survival for 72 h or respiratory depression defined as respiratory rate <15 breaths per minute, falling pulse oximetry, or agonal respirations. Fisher's exact t test was used for between group comparisons. Average time to toxicity for the saline control was 263 min (191-305 min). The development of respiratory depression occurred more frequently in control pigs than treated pigs (p = 0.009). Four of the six pigs that received trypsin survived to the end of the 3-day study. No control pigs survived. Two of the trypsin treatment pigs died with times to toxicity of 718 and 971 min. Survival to 12 and 24 h was significantly greater in the trypsin treatment group (p = 0.002, p = 0.009, respectively). Local injection of trypsin, a proteolytic enzyme, at the site of envenomation decreased the toxicity of eastern coral snake venom and increased survival significantly. Further investigation is required before these results can be extended to human snakebites.

Progression of age-related macular degeneration: association with dietary fat, transunsaturated fat, nuts, and fish intake.

BACKGROUND: Individuals with early or intermediate stages of age-related macular degeneration (AMD) make up a large, growing segment of the elderly population. Evidence is sparse regarding modifiable factors that may decrease the risk of progression to the advanced forms of AMD. OBJECTIVE: To advise patients with a high risk for advanced forms of AMD about preventive measures through our evaluation of the relationship between dietary fat intake and the progression of early or intermediate AMD to the advanced stages of the disease associated with visual loss. DESIGN: A prospective cohort study with an average follow-up time of 4.6 years. SETTING: A hospital-based clinical retinal practice specializing in macular degeneration. Patients The 261 participants were aged 60 years and older and had some sign of nonexudative AMD and visual acuity of 20/200 or better in at least 1 eye. Main Outcome Measure Progression to advanced AMD, which was defined as having geographic atrophy or neovascular disease. RESULTS: Higher total fat intake increased the risk of progression to the advanced forms of AMD, with a relative risk (RR) of 2.90 (95% confidence interval, 1.15-7.32) for the highest fat-intake quartile relative to the lowest fat-intake quartile, after controlling for other factors (P trend =.01). Animal fat intake was associated with a 2-fold increased risk of progression (RR, 2.29 for the highest quartile compared with the lowest quartile; 95% confidence interval, 0.91-5.72), although the trend for increasing risk with higher animal fat intake was not significant (P=.09). Higher vegetable fat intake had a stronger relationship with increased risk of AMD progression with an RR of 3.82 (95% confidence interval, 1.58-9.28) for the highest quartile compared with the lowest quartile (P trend =.003). Saturated, monounsaturated, polyunsaturated, and transunsaturated fats increased the likelihood of progression (RR, 2.09 and P trend =.08; RR, 2.21 and P trend =.04; RR, 2.28 and P trend =.04; RR, 2.39 and P trend =.008, respectively). Higher fish intake was associated with a lower risk of AMD progression among subjects with lower linoleic acid intake. Processed baked goods, which are higher in some of these fats, increased the rate of AMD progression approximately 2-fold, and nuts were protective. CONCLUSIONS: Among individuals with the early or intermediate stages of AMD, total and specific types of fat intake, as well as some fat-containing food groups, modified the risk of progression to advanced AMD. Fish intake and nuts reduced risk. Since advanced AMD is associated with visual loss and reduced quality of life, these preventive measures deserve additional research and greater emphasis.

Progression of age-related macular degeneration: association with body mass index, waist circumference, and waist-hip ratio.

BACKGROUND: Individuals with early or intermediate stages of age-related macular degeneration (AMD) make up a large and growing segment of our elderly population. To advise these high-risk patients regarding preventive measures, we evaluated anthropomorphic, behavioral, and medical factors associated with progression to the advanced stages of AMD associated with visual loss. METHODS: The design was a prospective cohort study in a hospital-based retinal practice. The 261 participants were 60 years or older, with some sign of nonadvanced AMD and visual acuity of 20/200 or better in at least 1 eye. The average follow-up time was 4.6 years, and the total person-years of follow-up was 1198. Factors associated with rates of progression to advanced AMD were assessed by the Cox proportional hazards model. OUTCOME MEASURES: Progression to geographic atrophy and neovascular disease. RESULTS: Higher body mass index (calculated as weight in kilograms divided by the square of height in meters) increased the risk for progression to the advanced forms of AMD. Relative risk (RR) was 2.35 (95% confidence interval [CI], 1.27-4.34) for a body mass index of at least 30, and 2.32 (95% CI, 1.32-4.07) for a body mass index of 25 to 29, relative to the lowest category (<25) after controlling for other factors (P =.007 for trend). Higher waist circumference was associated with a 2-fold increased risk for progression (RR for the highest tertile compared with the lowest, 2.04; 95% CI, 1.12-3.72), with a significant trend for increasing risk with a greater waist circumference (P =.02). Higher waist-hip ratio also increased the risk for progression (RR, 1.84; 95% CI, 1.07-3.15) for the highest tertile compared with lowest (P =.02 for trend). More physical activity tended to be associated with a reduced rate of progression (25% reduction for 3 times per week vigorous activity vs none, P =.05 to P =.07). Relative risks for smoking ranged from 1.48 to 1.99, but were not statistically significant. CONCLUSIONS: Results provide new information regarding modifiable factors for individuals with the early or intermediate stages of this disease. Overall and abdominal obesity increased the risk for progression to advanced AMD, and more physical activity tended to decrease risk. These preventive measures deserve additional research and greater emphasis.

Association between reproductive and hormonal factors and age-related maculopathy in postmenopausal women.

PURPOSE: The relationships between reproductive risk factors, including use of hormone replacement therapy and oral contraceptives and severity of age-related maculopathy (ARM) among postmenopausal women were evaluated. We hypothesized that exposure to endogenous or exogenous estrogens would be associated with a reduced risk of advanced ARM. DESIGN: Cross-sectional study. METHODS: The 394 subjects were postmenopausal women with ARM. Logistic regression analysis was used to compare the effects of several reproductive factors across two groups: 193 subjects with nonadvanced ARM and 201 subjects with advanced ARM. RESULTS: Women with ARM who had used postmenopausal estrogen therapy in the past had significantly lower odds of advanced ARM than nonusers, after controlling for other known and potential risk factors (odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.30 to 0.98). Older age at menarche was associated with increased odds of advanced ARM (OR = 1.16, 95% CI = 1.00 to 1.35). CONCLUSIONS: These findings suggest that exposure to exogenous estrogens may have a beneficial effect of reducing the risk of advanced types of ARM in postmenopausal women with ARM. Few therapeutic or preventive measures currently exist for ARM; therefore, these results deserve further evaluation.

A genomewide scan for age-related macular degeneration provides evidence for linkage to several chromosomal regions.

We report the results of a genomewide scan for age-related macular degeneration (AMD) in 158 multiplex families. AMD classification was based on fundus photography and was assigned a grade ranging from 1 (no disease) to 5 (exudative disease). Genotyping was performed by the National Heart, Lung, and Blood Institute Mammalian Genotyping Service at Marshfield (404 short tandem repeat markers). The sample included 158 families with two or more siblings with AMD, 490 affected individuals, 101 unaffected individuals, and 38 whose affection status was unknown. Relative pairs included 511 affected sibling, 28 avuncular, 53 cousin, 7 grandparent-grandchild, and 9 grand-avuncular pairs. Two-point parametric and multipoint parametric and nonparametric analyses were performed. Maximum two-point LOD scores of 1.0-2.0 were found for markers on chromosomes 1, 2, 8, 10, 14, 15, and 22. Multipoint analyses were consistent with the two-point results for chromosomes 1, 2, 8, 10, and 22 and provided evidence for additional linkage regions on chromosomes 3, 6, 8, 12, 16, and X. Our signals on chromosomes 1q, 6p, and 10q are consistent with some other previously published results. Significant linkage to AMD was found for one marker on chromosome 2, two adjacent markers on chromosome 3, two adjacent markers on chromosome 6, and seven contiguous markers on chromosome 8, with empirical P values of .00001. The consistency of many of the other signals across both two-point and multipoint, as well as parametric and nonparametric, analyses indicate several other regions worthy of follow-up.