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G J Myers

Publications and source records attributed to G J Myers.

At least 19 recordsLinked to original sources

Use of autologous blood as part of the perfusate for cardiopulmonary bypass: a priming technique.

In an attempt to replace the oncotic and protein coating capabilities of serum albumin in the perfusate, we established a priming protocol that used autologous blood as part of the perfusate solution. Prior to March 1, 1999, our standard priming protocol was 1650 ml of crystalloid with 250 ml of 5% serum albumin and 5,000 units of heparin. After removing albumin from our prime, our standard protocol was altered to include 40 ml of the patient's autologous blood in 1,800 ml of crystalloid and 10,000 units of heparin. To determine the intraoperative effects of using albumin/crystalloid primes (Group A), autologous blood/crystalloid primes (Group B) and crystalloid primes (Group C), a total of 178 patients were sequentially evaluated. Intraoperative parameters evaluated were total protein (TP), colloid osmotic pressure (COP), platelets (Plts) and fluid requirements during cardiopulmonary bypass (CPB). During an overlapping 12-month period of time, 1,092 consecutive cardiac surgical cases using CPB (584 albumin prime; 508 autologous blood prime) were evaluated for clinical outcomes in terms of mortality and length of hospitalization. In addition, over a period of 15 months, 1,458 patients in both the autologous blood/crystalloid group and the crystalloid only group were evaluated for the incidence of high-pressure excursions (HPE) after going on bypass. Comparative reviews of TP, COP and Plts demonstrated no significant difference 10 min after the start of bypass between Groups A and B. However, in Group C, there was a statistically significant increase in the intraoperative fluid requirements during CPB, compared to both of the other groups. There was no significant difference in the incidence of HPE, with an occurrence of 1.04% in the crystalloid only group and 1.11% in the autologous blood/crystalloid group. Autologous blood perfusates were identical to albumin perfusates in their platelet protection and reduction of fluid shifts during the intraoperative period.

Aged↗

Twenty-seven years studying the human neurotoxicity of methylmercury exposure.

Research at the University of Rochester (U of R) has been focused on mercury for nearly half a century. Initially studies focused on dosimetry, especially the accuracy of measuring exposure, and experimental work with animal models. Clinical studies in human populations started when the U of R mercury group was asked to assist with dosimetry in the Iraq epidemic of 1971-1972. Initial clinical studies described the effects of methylmercury (MeHg) poisoning on adults and children. A dose-response curve for prenatal exposure was determined and it suggested that relatively low exposures might be harmful to the fetus. Since most human exposure to MeHg is dietary from fish consumption, these theoretical dangers had far-reaching implications. After Iraq, the Rochester team pursued exposure from fish consumption in both adults and children. Populations with high fish consumption were identified in Samoa and Peru for studying adults and in Peru and the Seychelles islands for studying children. The possible health threat to the fetus from maternal fish consumption quickly became the focus of research efforts. This paper reviews the Rochester experience in studying human exposure to MeHg from fish consumption.

Adult↗

Association between methylmercury exposure from fish consumption and child development at five and a half years of age in the Seychelles Child Development Study: an evaluation of nonlinear relationships.

Studies to date of the developmental effects of pre- and postnatal methylmercury exposure from fish consumption in the Seychelles Islands, using linear regression models for analysis, have not shown adverse effects on neurodevelopmental test scores. In this study we evaluated whether nonlinear effects of methylmercury exposure were present, using scores on six tests administered to cohort children in the Seychelles Child Development Study at 66 months of age. Prenatal exposure was determined by measuring mercury in a segment of maternal scalp hair representing growth during pregnancy. Postnatal exposure was measured in a segment of the child's hair taken at 66-months of age. Generalized additive models (GAMs), which make no assumptions about the functional form of the relationship between exposure and test score, were used in the analysis. GAMs similar to the original linear regression models were used to reanalyze the six primary developmental endpoints from the 66-month test battery. Small nonlinearities were identified in the relationships between prenatal exposure and the Preschool Language Scale (PLS) Total score and Child Behavior Check List (CBCL) and between postnatal exposure and the McCarthy General Cognitive Index (GCI) test scores. The effects are best described graphically but can be summarized by computing the change in the predicted test score from 0 to either 10 or 15 ppm and then above this point. For the PLS the trend involved a decline of 0.8 points between 0 and 10 ppm followed by an increase (representing improvement) of 1.3 points above 10 ppm. For the CBCL there was an increase of 1 point from 0 to 15 ppm, and then a decline (improvement) of 4 points above 15 ppm. The GCI increased by 1.8 points through 10 ppm and then declined 3.2 points (representing worse performance) above 10 ppm. These results are not entirely consistent. Two of the trends involve what appear to be beneficial effects of prenatal exposure. The one possibly adverse trend involves postnatal exposure. In every case the trend changes direction, so that an effect in one direction is followed by an effect in the opposite direction. Because of the descriptive nature of GAMs it is difficult to provide a precise level of statistical significance for the estimated trends. Certainly above 10 ppm there is less data and trends above this level are estimated less precisely. Overall there was no clear evidence for consistent (across the entire range of exposure levels) adverse effects of exposure on the six developmental outcomes. Further nonlinear modeling of these data may be appropriate, but there is also the risk of fitting complex models without a clear biological rationale.

Animals↗

Neurodevelopmental outcomes of Seychellois children from the pilot cohort at 108 months following prenatal exposure to methylmercury from a maternal fish diet.

The Seychelles Child Development Study has been unable to confirm any relationship between maternal exposure to MeHg during pregnancy and adverse developmental outcomes. In this report, 87 children from a pilot cohort were evaluated at 9 years of age. Each child was given a battery testing specific cognitive, visual motor, and motor skills using standardized psychometric and neuro-psychological tests. The results indicated no adverse association between maternal MeHg exposure and any developmental outcome measure. For three endpoints (Boston Naming Test and two tests of visual motor coordination), enhanced performance in males was associated with increasing prenatal MeHg exposure. A secondary analysis including both prenatal MeHg and postnatal MeHg exposure was done even though we lacked postnatal hair for about 35% of the cohort. The results of the secondary analysis mirrored the outcomes of the primary analysis regarding prenatal exposure but were less robust. The results of this study are consistent with earlier findings from the 66-month evaluations of the SCDS Main cohort. Since MeHg is neurotoxic, this effect is likely due to other factors associated with consumption of fish.

Adult↗

Secondary analysis from the Seychelles Child Development Study: the child behavior checklist.

Human exposure to methylmercury (MeHg), a known neurotoxin, is primarily from fish consumption. As part of a large study examining the association between MeHg exposure and child development in a population with high fish consumption we examined school-age behavior using the Achenbach Child Behavior Checklist (CBCL). The CBCL Total T score was a primary endpoint and was reported earlier to show no adverse association with prenatal or postnatal MeHg exposure. In this study we analyzed the T scores of the CBCL subscales to determine if more discrete aspects of measured behavior were associated with exposure. The Seychelles Child Development Study (SCDS) is a prospective, double blind, longitudinal evaluation of over 700 children. The index of prenatal exposure was maternal hair total mercury (T-Hg) in a segment growing during gestation. Postnatal exposure was T-Hg in the child's hair taken at 66 months of age. The child's primary caregiver completed the CBCL during the 66-month evaluation. No association between prenatal or postnatal MeHg exposure and the CBCL subscales was found. In Seychellois children exposed to MeHg from consumption of ocean fish we found no association between either prenatal or postnatal MeHg exposure and behavior as measured by the CBCL subscales.

Adult↗

Association between prenatal exposure to methylmercury and cognitive functioning in Seychellois children: a reanalysis of the McCarthy Scales of Children's Ability from the main cohort study.

Methylmercury (MeHg) is a neurotoxicant whose high-dose effects first became known following a number of poisoning outbreaks that occurred worldwide. The primary human exposure is low dosage from fish consumption. Studies of fish-eating populations have not found a consistent pattern of association between exposures and outcomes. Therefore, examining specific areas of cognitive functioning has been suggested as an important approach to determine whether more subtle effects of MeHg exposure are present. In the Seychelles longitudinal study of prenatal and postnatal MeHg exposure from fish consumption and development, the McCarthy Scales of Children's Abilities (MSCA) were administered to children at age 66 months. No association between MeHg exposure and performance on the MSCA General Cognitive Index was identified. We analyzed these data further to determine whether associations were present on specific subscales of the MSCA. The standard MSCA subscales were analyzed. Then, more specific subscales of the MSCA were defined and analyzed utilizing a neuropsychological approach. The subscales were recombined to approximate the domains of cognitive functioning evaluated in the Faroes and New Zealand studies. Analyses of both the standard and the recombined MSCA subscales showed no adverse associations with MeHg exposure and neuropsychological endpoints. A positive association between postnatal MeHg exposure and performance on the MSCA Memory subscale was found. These findings are consistent with previous reports from the Seychelles study in that no adverse effects of MeHg exposure from fish consumption can be detected in this cohort.

Animals↗

Simple modified ultrafiltration.

After reviewing all available methods of modified ultrafiltration (MUF), an attempt was made to develop a more simplified approach to this beneficial method of post-bypass fluid removal by withdrawing blood from the right atrium and reinfusing into the aortic cannula (venoarterial). The simplicity of operation, ease of setup and analysis of hemoglobin, hematocrit, total proteins and colloid osmotic pressure, and fluid removed were examined in 12 consecutive neonatal and pediatric patients undergoing cardiac surgery. Results indicate that this simplified modified ultrafiltration (SMUF) is comparable to all other methods of MUF by achieving dramatic improvements in all parameters measured. In addition, SMUF provides the perfusionist with the ability to run conventional ultrafiltration throughout the bypass procedure, using this one circuit design. As well as finding the learning curve for SMUF to be very short, this method was found to be superior in its simplicity of operation, ease of setup, reduced risk of complications and acceptance by the surgeon and anesthetist.

Aorta↗

Benchmark concentrations for methylmercury obtained from the Seychelles Child Development Study.

Methylmercury is a neurotoxin at high exposures, and the developing fetus is particularly susceptible. Because exposure to methylmercury is primarily through fish, concern has been expressed that the consumption of fish by pregnant women could adversely affect their fetuses. The reference dose for methylmercury established by the U.S. Environmental Protection Agency was based on a benchmark analysis of data from a poisoning episode in Iraq in which mothers consumed seed grain treated with methylmercury during pregnancy. However, exposures in this study were short term and at much higher levels than those that result from fish consumption. In contrast, the Agency for Toxic Substances and Disease Registry (ATSDR) based its proposed minimal risk level on a no-observed-adverse-effect level (NOAEL) derived from neurologic testing of children in the Seychelles Islands, where fish is an important dietary staple. Because no adverse effects from mercury were seen in the Seychelles study, the ATSDR considered the mean exposure in the study to be a NOAEL. However, a mean exposure may not be a good indicator of a no-effect exposure level. To provide an alternative basis for deriving an appropriate human exposure level from the Seychelles study, we conducted a benchmark analysis on these data. Our analysis included responses from batteries of neurologic tests applied to children at 6, 19, 29, and 66 months of age. We also analyzed developmental milestones (age first walked and first talked). We explored a number of dose-response models, sets of covariates to include in the models, and definitions of background response. Our analysis also involved modeling responses expressed as both continuous and quantal data. The most reliable analyses were considered to be represented by 144 calculated lower statistical bounds on the benchmark dose (BMDLs; the lower statistical bound on maternal mercury hair level corresponding to an increase of 0.1 in the probability of an adverse response) derived from the modeling of continuous responses. The average value of the BMDL in these 144 analyses was 25 ppm mercury in maternal hair, with a range of 19 to 30 ppm.

Animals↗

Does methylmercury have a role in causing developmental disabilities in children?

Methylmercury (MeHg) is a potent neurotoxin that in high exposures can cause mental retardation, cerebral palsy, and seizures. The developing brain appears particularly sensitive to MeHg. Exposure levels in pregnant experimental animals that do not result in detectable signs or symptoms in the mother can adversely affect the offspring's development. Studies of human poisonings suggest this may also occur in humans. Human exposure to MeHg is primarily dietary through the consumption of fish: MeHg is present in all fresh and saltwater fish. Populations that depend on fish as a major source of dietary protein may achieve MeHg exposure levels hypothesized to adversely affect brain development. Increasing mercury levels in the environment have heightened concerns about dietary exposure and a possible role for MeHg in developmental disabilities. Follow-up studies of an outbreak of MeHg poisoning in Iraq revealed a dose-response relationship for prenatal MeHg exposure. That relationship suggested that prenatal exposure as low as 10 ppm (measured in maternal hair growing during pregnancy) could adversely affect fetal brain development. However, using the same end points as were used in the Iraq study, no associations have been reported in fish-eating populations. Using a more extensive range of developmental end points, some studies of populations consuming seafood have reported associations with prenatal MeHg exposure, whereas others have found none. This paper reviews the data presently available associating MeHg exposure with development and poses some of the unanswered questions in this field.

Animals↗

Evaluation of techniques for assessing neurobehavioral development in children.

A battery of tests has been designed to explore functional disabilities in children 10-12 years of age arising from adverse conditions during early development. At these ages, it becomes possible to use more complex and challenging tests than those typically used at earlier ages. Although the battery was prompted originally by questions arising from methylmercury exposure, it was also designed for applicability to neurotoxicant exposures arising from pesticides, solvents, persistent organic pollutants such as PCBs and dioxins, other metals, and nutrient excesses and deficiencies as well. The test battery includes the following categories: (1) neuropsychological tests with established psychometric properties not widely exploited in studies of developmental neurotoxicity; (2) electrophysiological and behavioral tests of sensory functioning spanning a broader range of indices than those used generally in studies of neuropsychological development; and (3) adaptations of performance tasks used previously only in animals. The battery was developed in Rochester, New York, and then field-tested on a group of 61 children in the Republic of the Seychelles, where the Ministry of Health had established the Child Development Center. Our findings suggest a number of tests and procedures with the potential for inclusion in test batteries aimed at the exploration of adverse neurodevelopmental effects.

Adolescent↗

Double valve replacement in a patient with anticardiolipin antibody syndrome.

Cardiopulmonary bypass (CPB) was used during the replacement of the aortic and mitral valves in a 43-year-old female patient. The case was complicated by the presence of a rare hypercoagulable condition called anticardiolipin (antiphospholipid) antibody syndrome. The course of bypass was uneventful and the patient was released from the intensive care unit on the first postoperative day. CPB in the presence of anticardiolipin antibodies is an unusual situation that requires diligent hematological monitoring. Since 1989 there have been only 14 reported cases of these antibodies and cardiopulmonary bypass. Eight of these have involved valve replacements.

Adult↗

Avoiding hyperoxemia at the start of cardiopulmonary bypass while optimizing gas flow and temperature.

There seems to be a wide range of practice in relation to the optimum oxygen setting before, and at the start of, cardiopulmonary bypass. Even manufacturers of blood oxygenators vary in their suggestions for this phase of extracorporeal circulation. Most of these suggestions are based on peak performance, Association for the Advancement of Medical Instrumentation (AAMI) standards, experience, and legal considerations. Therefore, suggested gas:blood flow ratios will vary from no gas flow at the start of bypass, to a ratio setting of 1:1. On the other hand, suggested inspired oxygen concentrations will generally vary between 0.80 to 1.0 at the start of cardiopulmonary bypass. In regard to perfusate temperatures before going on bypass, there are no clearly defined standards other than those of clinical preference. The manufacturer of the oxygenator used in this study clearly states in the operating instructions that gas flow should be proportional to blood flow at the start of bypass, and gas flow should be turned off when there is no fluid flow through the oxygenator. The presence of hyperoxic perfusates and wide patient/perfusate temperature gradients at the start of bypass has been suspected in the appearance of gaseous microemboli during this critical period. Hyperoxemia during the bypass period is also implicated in the introduction of oxygen free radicals and nitric oxide into the hypoxic myocardium during cardioplegia delivery. Presented here are the results of a randomized clinical study involving 39 adult patients undergoing cardiopulmonary bypass for the surgical treatment of coronary artery disease. All patients were randomly selected into five groupings. The first group had 1 L of gas flow through the perfusate before bypass, and bypass was then started with an FIO2 of 0.80. The second two groups had no gas flow through the perfusate prior to bypass and a starting FIO2 of 0.21. Groups 4 and 5 had 1 L of gas flowing through the perfusate and a starting FIO2 of 0.21. Results indicate that gas flow through Normosol R/Albumin perfusates will prevent the acidosis that is found in this solution when the system is previously flushed with carbon dioxide. Also, suggested high FIO2 settings will produce hyperoxic perfusates at the start of cardiopulmonary bypass. However, the use of an FIO2 of 0.21 at the start of bypass will produce normoxemic conditions that are both safe and reliable for the conduct of initiating cardiopulmonary bypass.

Adult↗

Effects of prenatal and postnatal methylmercury exposure from fish consumption on neurodevelopment: outcomes at 66 months of age in the Seychelles Child Development Study.

CONTEXT: Human neurodevelopmental consequences of exposure to methyl-mercury (MeHg) from eating fish remain a question of public health concern. OBJECTIVE: To study the association between MeHg exposure and the developmental outcomes of children in the Republic of Seychelles at 66 months of age. DESIGN: A prospective longitudinal cohort study. PARTICIPANTS: A total of 711 of 779 cohort mother-child pairs initially enrolled in the Seychelles Child Development Study in 1989. SETTING: The Republic of Seychelles, an archipelago in the Indian Ocean where 85% of the population consumes ocean fish daily. MAIN OUTCOME MEASURES: Prenatal and postnatal MeHg exposure and 6 age-appropriate neurodevelopmental tests: the McCarthy Scales of Children's Abilities, the Preschool Language Scale, the Woodcock-Johnson Applied Problems and Letter and Word Recognition Tests of Achievement, the Bender Gestalt test, and the Child Behavior Checklist. RESULTS: The mean maternal hair total mercury level was 6.8 ppm and the mean child hair total mercury level at age 66 months was 6.5 ppm. No adverse outcomes at 66 months were associated with either prenatal or postnatal MeHg exposure. CONCLUSION: In the population studied, consumption of a diet high in ocean fish appears to pose no threat to developmental outcomes through 66 months of age.

Central Nervous System Diseases↗

Mercury in fish.

Explore the source record for details and available documents.

Animals↗

X-linked female band heterotopia-male lissencephaly syndrome.

We report a family with band heterotopia in a mother and daughter and lissencephaly in a son (X-linked inheritance pattern). Postmortem examination of the boy revealed classical lissencephaly and, among other findings, simplified and discontinuous inferior olives without inferior olivary heterotopia. The absence of inferior olivary heterotopia may distinguish X-linked lissencephaly from other conditions with classic lissencephaly such as Miller-Dieker syndrome.

Adult↗

Semiparametric modeling of age at achieving developmental milestones after prenatal exposure to methylmercury in the Seychelles child development study.

Controversy exists concerning the fetal risk associated with exposure to low-dose methylmercury from maternal fish consumption. Previous studies of the effects of acute prenatal mercury exposure identified delays in achieving developmental milestones among exposed children. This led to public health concern that prenatal low-dose exposure from fish consumption could adversely affect the fetus. We evaluated the effects of prenatal methylmercury exposure (through maternal fish consumption) on the age that children walked and first said words in the main study cohort of the Seychelles Child Development Study. We used semiparametric generalized additive models to identify nonlinearities in the relationships between prenatal exposure and developmental outcomes, after adjusting for covariates, and to evaluate their importance. Very slight delays (<1 day) in walking were seen as mercury levels increased from 0 to 7 ppm, but this effect did not persist at the higher exposure levels represented by the cohort, making it difficult to conclude that a cause and effect relationship existed at the exposure levels seen in this cohort. There was no evidence for any association between prenatal exposure and age at talking.

Child Development↗