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Background: Patients with chronic kidney disease (CKD) have poor outcomes following myocardial infarction (MI). We performed an untargeted examination of 175 biomarkers to identify those with the strongest association with CKD and to examine the association of those biomarkers with long-term outcomes.Methods: A total of 175 different biomarkers from MI patients enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry were analysed either by a multiple reaction monitoring mass spectrometry assay or by a multiplex assay (proximity extension assay). Random forests statistical models were used to assess the predictor importance of biomarkers, CKD and outcomes.Results: A total of 1098 MI patients with a median estimated glomerular filtration rate of 85 mL min-1 /1.73 m2 were followed for a median of 3.2 years. The random forests analyses, without and with adjustment for differences in demography, comorbidities and severity of disease, identified six biomarkers (adrenomedullin, TNF receptor-1, adipocyte fatty acid-binding protein-4, TNF-related apoptosis-inducing ligand receptor 2, growth differentiation factor-15 and TNF receptor-2) to be strongly associated with CKD. All six biomarkers were also amongst the 15 strongest predictors for death, and four of them were amongst the strongest predictors of subsequent MI and heart failure hospitalization.Conclusion: In patients with MI, a proteomic approach could identify six biomarkers that best predicted CKD. These biomarkers were also amongst the most important predictors of long-term outcomes. Thus, these biomarkers indicate underlying mechanisms that may contribute to the poor prognosis seen in patients with MI and CKD. [ABSTRACT FROM AUTHOR]

Background and purpose Mutations in the glucocerebrosidase ( GBA) gene are known to be a risk factor for Parkinson's disease ( PD). Data on clinicopathological correlation are limited. The purpose of this study was to determine the clinicopathological findings that might distinguish PD cases with and without mutations in the GBA gene. Methods Data from the Arizona Study of Aging and Neurodegenerative Disorders were used to identify autopsied PD cases that did or did not have a GBA gene mutation. Clinical and neuropathological data were compared. Results Twelve PD cases had a GBA mutation and 102 did not. The GBA mutation cases died younger (76 vs. 81 years of age) but there was no difference in disease duration or clinical examination findings. No neuropathological differences were found in total or regional semi-quantitative scores for Lewy-type synucleinopathy, senile plaques, neurofibrillary tangles, white matter rarefaction or cerebral amyloid angiopathy scores. Conclusions In longitudinally assessed, autopsied PD cases, those with GBA mutations had a younger age at death but there was no evidence for clinical or neuropathological differences compared to cases without GBA mutations. Due to the small GBA group size, small differences cannot be excluded. [ABSTRACT FROM AUTHOR]

Background and purpose Susceptibility to multiple sclerosis ( MS) is determined by environmental and genetic factors, but the cause remains unknown. Changes to the proteome prior to first symptom onset may reflect the underlying pathophysiology of the disease. Methods This preliminary study utilized pre-symptomatic and post-symptomatic serum from a sample of 100 incident population-based US military veterans with MS along with 100 matched healthy controls. All samples were obtained from the Department of Defense Serum Repository. Multidimensional protein identification technology tandem mass spectrometry analysis was performed on tryptic peptides of lectin-captured glycosylated serum proteins following albumin/immunoglobulin G depletion. Identified proteins were analyzed with the Ingenuity Pathway Analysis program. Results The mean intervals between first symptom onset and the collection of pre-symptomatic and post-symptomatic sera were −6.0 and +1.1 years, respectively. Pre-symptomatic proteins from the MS group were differentially regulated compared with both control groups indicating that proteomic changes are detected prior to symptom onset. Pathway analysis showed that proteins involved in the complement and coagulation pathways and lipid transport are significantly altered in the serum of subjects with MS compared with healthy donors. Conclusions Compared with healthy controls, differential proteomic changes were noted in the serum of patients with MS that preceded the onset of symptomatic disease. Further work is in progress to confirm or refute these findings. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease ( CKD) display a high prevalence of cardiovascular events and acute infections. Potential effector cells are the CD16+ monocytes, known to be increased in the peripheral circulation in CKD. The aim of this study was to assess the expression of CD16 and CX3 CR1 on peripheral and in vivo extravasated monocytes in patients with CKD ( GFR < 20 ml/min × 1.73 m²) using flow cytometry. In vivo extravasated monocytes were collected from a local inflammatory site, induced by a skin blistering technique. Soluble markers were assessed by Luminex. The number of CD16+ monocytes was significantly higher in patients with CKD compared with healthy subjects, both in the peripheral circulation ( P < 0.05) and at the site of induced inflammation ( P < 0.001). Patients with CKD displayed significantly higher concentration of soluble CX3 CL1 both in the peripheral circulation ( P < 0.01) and in the interstitial fluid ( P < 0.001). In addition, patients with CKD had a significantly higher concentration of TNF-α in the peripheral circulation ( P < 0.001). On the contrary, at the inflammatory site, concentrations of both TNF-α and IL-10 were significantly lower in patients with CKD compared with healthy controls ( P < 0.05 for both). In conclusion, patients with CKD have an increased percentage of CD16+ monocytes in both circulation and at the inflammatory site, and this finding is in concurrence with simultaneous changes in CX3 CR1. Together with distorted TNF-α and IL-10 levels, this may have potential impact on the altered inflammatory response in CKD. [ABSTRACT FROM AUTHOR]

Severe blinding retinal degenerative diseases have been without treatments that could improve vision until recently. Gene therapy has been in clinical trials for certain inherited retinopathies in which photoreceptors are retained despite severe visual loss. Optogenetics is being discussed for retinal diseases in which there is severe visual loss and nearly complete photoreceptor cell death. As a retinal therapy, optogenetics would be the genetic targeting of light-sensing molecules to residual cells in a degenerate retina. Parallel with scientific advances in optogenetics should be the development of detailed criteria for patient candidacy. Here, molecularly defined retinal degenerations are used to exemplify how some diseases or stages of disease would satisfy the criteria. Measurements are made of the thickness of ganglion cell and the nerve fiber layers of the retina. Whereas the clinical category of retinitis pigmentosa has been most often mentioned for treatment by optogenetics, an argument is made for expanding the target diseases to some early-onset disorders diagnosed as Leber congenital amaurosis. [ABSTRACT FROM AUTHOR]

The cellular and soluble mediators of a dermal inflammation can be studied by the skin chamber technique. The aim of this study was to address the physiological effect of soluble mediators, released into the skin chamber, with special focus on neutrophil CD11b activation. Mediators released at the inflammatory site were studied by Milliplex and enzyme-linked immunosorbent assay (ELISA) and correlated with transmigration and CD11b activation in vivo and in vitro. Transmigration was studied by the skin chamber technique and by the transwell method, and expression of the CBRM1/5 epitope on activated CD11b was analysed by flow cytometry following in vivo and in vitro incubation with chamber fluid or recombinant interleukin-8 (IL-8). Leucocyte in vivo and in vitro transmigration both correlated with the concentrations of IL-1β, tumour necrosis factor alpha (TNFα) and IL-8 at P < 0.05 ( R > 0.7). Furthermore, CD11b was activated, in terms of exposure of the activation epitope, on neutrophils after 30 min of in vitro incubation with chamber fluid and correlated solely with the concentration of IL-8, P < 0.05 ( R = 0.72). In vitro incubation with recombinant IL-8 confirmed a concentration-dependent expression of the activation epitope; however, induction of CBRM1/5 by recombinant IL-8 required a concentration that was significantly higher compared with that in chamber fluid. In addition, the CBRM1/5 epitope was analysed on in vivo extravasated neutrophils that displayed a significantly higher expression compared with circulating neutrophils, P = 0.04. We conclude that IL-8 is the major factor regulating the expression of CD11b activation epitope in neutrophils. [ABSTRACT FROM AUTHOR]

Szummer K, Lundman P, Jacobson SH, Schön S, Lindbäck J, Stenestrand U, Wallentin L, Jernberg T, for SWEDEHEART. (Karolinska Institute, Karolinska University Hospital, Stockholm; Karolinska Institute, Danderyd Hospital, Danderyd; Ryhov County Hospital, Jönköping; University Hospital, Uppsala and University Hospital, Linköping; Sweden) Relation between renal function, presentation, use of therapies and in-hospital complications in acute coronary syndrome: data from the SWEDEHEART register. J Intern Med 2010; 268:40–49. Objective. To examine clinical characteristics, presenting symptoms, use of therapy and in-hospital complications in relation to renal function in patients with myocardial infarction (MI). Design. Observational study. Setting. Nationwide coronary care unit registry between 2003–2006 in Sweden. Subjects. Consecutive MI patients with available creatinine ( n = 57 477). Results. Glomerular filtration rate was estimated with the Modification of Diet in Renal Disease Study formula. With declining renal function patients were older, had more co-morbidities and more often used cardio-protective medication on admission. Compared to patients with normal renal function, fewer with renal failure presented with chest pain (90% vs. 67%, P < 0.001), Killip I (89% vs. 58%, P < 0.001) and ST-elevation myocardial infarction (STEMI) (41% vs. 22%, P < 0.001). In a logistic regression model lower renal function was independently associated with a less frequent use of anticoagulant and revascularization in non-ST-elevation MI. The likelihood of receiving reperfusion therapy for STEMI was similar in patients with normal-to-moderate renal dysfunction, but decreased in severe renal dysfunction or renal failure. Reperfusion therapy shifted from primary percutaneous coronary intervention in 71% of patients with normal renal function to fibrinolysis in 58% of those with renal failure. Renal function was associated with a higher rate of complications and an exponential increase in in-hospital mortality from 2.5% to 24.2% across the renal function groups. Conclusion. Renal insufficiency influences the presentation and reduces the likelihood of receiving treatment according to current guidelines. Short-term prognosis remains poor. [ABSTRACT FROM AUTHOR]

A human islet transplant can cure patients with type 1 diabetes. A drawback of islet transplantation is the life-long immunosuppressive medication, often associated with severe side effects. Moreover, in spite of the immunosuppressive therapy, islets are lost in the majority of transplanted patients over time. An improved small animal model for studies on human islet allograft rejection mechanisms and the development of new measures for its prevention is clearly warranted. Here, we evaluated the potential of Balb/cRag2−/−γc−/− mice carrying a human-like immune system (so-called humanized mice) as a tool for studies on the rejection of transplanted human islets. Human T cells from Balb/cRag2−/−γc−/− mice, which as neonates had been transplanted with CD34+ human cord blood haematopoietic stem cells (HIS mice), proliferated in response to allogeneic human dendritic cells, but failed to reject a human islet allograft transplanted to the renal subcapsular space as assessed by immunohistochemistry and analysis of human serum C-peptide levels. Histological analysis revealed that few if any T cells had migrated to the grafted tissue. These observations question the usefulness of the HIS mouse model for studies on human islet allograft rejection mechanisms and highlight the need for further improvements. [ABSTRACT FROM AUTHOR]

The phenotypic alterations in monocytes induced by extravasation in vivo are still largely unknown. We addressed the question whether a general phenotype of extravasated monocytes exists and whether this phenotype differs between healthy individuals and statin treated patients with coronary artery disease (CAD). In vivo extravasated monocytes from CAD patients and healthy controls were collected by use of the skin blister method and compared with peripheral circulating monocytes by flow cytometry. The number of CD14+CD16+ monocytes were significantly higher in the skin blister compared with peripheral circulation in both patients ( P < 0.001) and controls ( P = 0.005). In vivo extravasated monocytes had in comparison with peripheral monocytes a lower expression of CX3CR1, a higher expression of HLA-DR, CD86 and CD36 and a higher binding of acetylated low density lipoprotein (acLDL) (significant for all markers). Skin blister fluid from CAD patients, compared with healthy controls, induced a 20% increase in monocyte CD36 expression ( P = 0.008) following 18 h of in vitro incubation. The results indicate that the integrated response to the in vivo extravasation process is similar in statin treated stable CAD patients and healthy controls, with respect to phenotypic alterations. Such differences in CAD patients may, however, occur as a response to the inflammatory milieu. [ABSTRACT FROM AUTHOR]

Structured Abstract Authors – Fang S, McLaughlin J, Fang J, Huang J, Autti-Rämö I, Fagerlund Å, Jacobson SW, Robinson LK, Hoyme HE, Mattson SN, Riley E, Zhou F, Ward R, Moore ES, Foroud T, and the Collaborative Initiative on Fetal Alcohol Spectrum Disorders. Objectives – Use three-dimensional (3D) facial laser scanned images from children with fetal alcohol syndrome (FAS) and controls to develop an automated diagnosis technique that can reliably and accurately identify individuals prenatally exposed to alcohol. Methods – A detailed dysmorphology evaluation, history of prenatal alcohol exposure, and 3D facial laser scans were obtained from 149 individuals (86 FAS; 63 Control) recruited from two study sites (Cape Town, South Africa and Helsinki, Finland). Computer graphics, machine learning, and pattern recognition techniques were used to automatically identify a set of facial features that best discriminated individuals with FAS from controls in each sample. Results – An automated feature detection and analysis technique was developed and applied to the two study populations. A unique set of facial regions and features were identified for each population that accurately discriminated FAS and control faces without any human intervention. Conclusion – Our results demonstrate that computer algorithms can be used to automatically detect facial features that can discriminate FAS and control faces. [ABSTRACT FROM AUTHOR]

In vitro studies have demonstrated that antineutrophil cytoplasmic antibodies (ANCA) have the capacity to activate neutrophils. Whether circulating neutrophils in patients with vasculitis are activated is under debate. Eight consecutive patients with antiproteinase 3 (PR3) positive acute vasculitis were included in this prospective study. Neutrophil expression of adhesion molecules, Fc-receptors and the ANCA-antigen PR3 was analysed and clinical characteristics were documented at inclusion and after 1, 3, 6 and 9 months in the same individuals. As additional markers of inflammation and endothelial activation interleukin-8 and soluble vascular cell adhesion molecule-1 in serum were analysed at the same time points. The expression of adhesion molecules on circulating neutrophils, CD62L and CD11b after in vitro N-formyl-methionyl-leucyl-phenylalanine stimulation was significantly decreased at diagnosis and after 1 month but returned to normal levels after 3–9 months. The neutrophil expression of Fc-receptor IIIb (CD 16) was decreased at diagnosis but normalized after 1–9 months. The main finding was an activated neutrophil adhesion phenotype at diagnosis and after 1 month, with normalized expression of adhesion molecules at 3–9 months. A pathological regulation of adhesion molecules may have implications on the endothelial damage seen in vasculitis. [ABSTRACT FROM AUTHOR]

Severe sepsis and septic shock are associated with high mortality rates. Data on sepsis outcome from Scandinavian countries are sparse. The aim of this study was to examine the length of stay (LOS) in the ICU, ICU mortality and costs of care for adult patients with primary sepsis in a university hospital in northern Sweden. We performed a retrospective data analysis of records of 92 patients admitted over a 3-year period, under the diagnosis of sepsis or urosepsis. Demographic data, admission category, APACHE II score, aetiology and severity of sepsis, ICU LOS, mortality and TISS were analyzed. Eighty-one adult patients were identified by standard definitions as suffering from sepsis. The median ICU length of stay was 4.2 days, 6 days for survivors and 2.1 days for non-survivors. Thirteen out of 20 deaths occurred within the first 3 days after admission. Overall ICU mortality rate was 24.7% while the ICU mortality for patients with septic shock was 57.7%. The mean costs of care for patients with sepsis were 3139 Euros day−1 and the cost of care per patient surviving sepsis was 38 494 Euros. The incidence of primary sepsis in our ICU was low. Previous reports on high mortality in association with severe sepsis and septic shock are valid also at our hospital. The ICU-LOS was shorter than previously reported, while our costs of care were in the same range as stated by others. This retrospective analysis is valid for interpretation of the applicability of currently available sepsis therapies. [ABSTRACT FROM AUTHOR]

Abstract Monocyte in vitro activation by antimyeloperoxidase (anti-MPO)- and antiproteinase-3 (anti-PR3)-positive sera, corresponding immunoglobulin G (IgG) fractions and monoclonal antibodies against MPO and PR3 was evaluated. The expression of adhesion molecules, l-selectin (CD62L) and CR3 (CD11b), involved in leucocyte endothelial adhesion, and metabolic activity, measured as the production of hydrogen peroxide, were analysed. Decreased expression of CD62L was demonstrated in monocytes after incubation with antineutrophil cytoplasmic antibody (ANCA)-positive sera. This finding was not accompanied by changes in CD11b expression. Metabolic activity was increased in monocytes after incubation with ANCA-positive IgG fractions as well as after incubation with monoclonal anti-MPO and anti-PR3. These findings support the concept that the pathophysiological effect of ANCA is partly mediated through the action on crucial events in monocyte activation, such as CD62L downregulation and oxygen radical production. [ABSTRACT FROM AUTHOR]

Assesses visual expectation in 103 black 6.5-month-olds using Haith, Hazan and Goodman's paradigm and related it to performance on standard developmental assessments and tests of information processing skill. Relation to fixation duration on both visual recognition memory (VRM) and cross-modal transfer; Methods; Results; Discussion; Conclusion.

This article focuses on automatic syntax analysis in machine indexing and abstracting. The approach presented here is an analysis of the language in the modern linguistic sense by formalizing the rules of natural language structure, recognizing the elements that are permitted in this structure, and manipulating these elements in a systematic way to achieve a standard form of discourse which will then and only then yield to semantic analysis, and finally if necessary, to statistical analysis. Automatic syntax analysis is used here to describe a method of mechanizing the recognition of the phrase structure of English and some of the relations between clauses in the sentence. The type of analysis done in the automatic syntax analysis program is only the first step in the systematic approach to the problem of mechanizing operations on natural language for indexing and abstracting.

Determines the influence of breast feeding during infancy on the intellectual development of the child after control for socio-environmental factors. Cognitive and motor performance of small-for-gestational-age (SGA) children; Nutritional value of breast milk for SGA infants; Influence of the genetic and socio-environmental input of the mother.

The article presents an abstract of the study "Abnormalities in Plasma Lipoprotein and Red Blood Cell Phospholipids in Retinitis Pigmentosa (RP) Due to a Rod Photoreceptor Specific Gene Defect," which will be presented at the 30th Annual Meeting of the American Society for Neurochemistry to be held from March 14-17, 1999 in New Orleans, Louisiana. The study concludes that systemically detectable lipid abnormalities can occur in RP caused by a photoreceptor gene mutation.

Human T-cell leukemia virus type 1 (HTLV-1) is associated with adult T-cell leukemia-lymphoma (ATLL) in about 5% of infected individuals. Coinfection by Strongyloides stercoralis has been suggested to be a cofactor for development of ATLL. We describe a patient who presented with HTLV-1-associated chronic ATLL and Strongyloides infection. Studies of this patient's viral RNA levels demonstrated stimulation of HTLV-1 replication by Strongyloides, which resolved with anti-helminthic therapy. This case provides support for the hypothesis that Strongyloides is a cofactor for ATLL via T-cell stimulation.

Background: Although many studies have examined the development of children of male alcoholics, few studies have considered substance use by the female caregiver. This study evaluated the relationship between substance use by female caregivers and factors that affect the child-rearing environment., Methods: A total of 480 inner-city African-American women were recruited during pregnancy for a longitudinal study of the effects of prenatal alcohol use and substance use by caregivers on the development of their children. All women were screened for alcohol consumption at their first prenatal visit to a large urban maternity hospital. Those who averaged seven or more drinks per week (0.5 oz absolute alcohol per day) at the time of conception were invited to participate in the study, as was a 5% random sample of lighter drinkers and abstainers. At the 7.5-year follow-up assessment, the quantity and frequency of alcohol consumption and drug use, as well as several measures of the child-rearing environment, were assessed for 231 of the caregivers., Results: Current alcohol use was uncorrelated with standard demographic factors, such as socioeconomic status, but was related to poorer family functioning, lower quality of parental intellectual stimulation, and higher levels of domestic violence. There were independent effects of illicit drug use on family environment, domestic violence, and caregiver depression. History of drinking during pregnancy, however, was not related to the current child-rearing environment. Poorer parental functioning generally was found only among the caregivers who currently drank both heavily (six or more drinks/occasion) and frequently (three or more days/week). After controlling for lifetime alcohol problems, current drinking still predicted a less cohesive and organized family environment and higher levels of domestic violence., Conclusions: Current heavy, frequent drinking in this relatively homogenous, economically disadvantaged sample was unrelated to demographics and seemed to have an important negative impact on the quality of the child-rearing environment, whereas drinking during pregnancy was unrelated to the current child-rearing environment.

A current issue in alcohol research is whether a "neurobehavioral profile" can be identified for prenatal alcohol exposure, even when dysmorphic features are not present, or whether comparable neurobehavioral deficits are detected when damage is incurred by numerous neurotoxicants to which the fetus is exposed during a common developmental period. Failure to detect such differences may, in part, be an artifact of the global developmental tests used to assess outcome. Cognitive effects of prenatal exposure to three different teratogens [polychlorinated biphenyls (PCBs), alcohol, and cocaine] are examined to determine whether exposure to each substance results in a common or different pattern of impairment on the same set of newer, more narrow band infant tests. Comparison of findings from three independent cohorts indicate that PCB exposure was related to poorer recognition memory on the Fagan Test of Infant Intelligence (FTII) in Michigan infants exposed prenatally to PCB-contaminated fish, whereas prenatal alcohol exposure was unrelated to recognition memory but to slower processing speed on a new FTII measure and slower reaction time on Haith's Visual Expectancy Paradigm (VExP) in our Detroit alcohol-exposed infants. Preliminary findings from a new study of infants recently born to Taiwanese women accidentally contaminated with sizable amounts of PCBs indicate recognition memory deficits, confirming our Michigan findings, but no processing speed effects on the FTII. Recent findings from our Detroit cohort suggest that heavy prenatal cocaine exposure is related to poorer recognition memory on the FTII, but faster reaction times on the VExP, a pattern different from that seen for either PCBs or alcohol.

Prospective studies of the effects of prenatal alcohol exposure on development have focused primarily on the detection of subtle deficits. This study was designed to extend those findings by evaluating dose-response, functional significance, and pattern of drinking in greater detail. 480 African-American infants, recruited to overrepresent prenatal exposure at moderate-to-heavy levels, were assessed. For the five outcomes tested, nonparametric and hockey stick regression analyses both indicated essentially no relation between pregnancy drinking and developmental outcome below a median threshold of 0.5 oz absolute alcohol/day, with the impact of the exposure increasing gradually above threshold. Functional deficit was defined in terms of performance in the bottom 10th percentile of the distribution. For four of the five outcomes tested, there was no increased incidence of functionally significant deficit in infants born to moderate-to-heavy drinking mothers <30 years old, whereas those born to older drinking mothers were 2 to 5 times more likely to be functionally impaired. Among the infants exposed above threshold, functionally significant deficits were seen primarily in those whose mothers averaged at least 5 drinks/occasion on an average of at least once/week. By contrast, a history of alcohol abuse was not related to functional deficit. These data suggest that efforts to reduce the incidence of alcohol-related functional impairment should specifically target the older mother who engages in intermittent heavy drinking during pregnancy.

The risk of fetal alcohol syndrome (FAS) is known to increase with increased maternal age and parity. This study investigated the hypothesis that the deficits in growth and intellectual function seen in non-FAS infants exposed to alcohol at moderate-to-heavy levels are also found disproportionately in the offspring of older mothers. Mothers of 480 African-American, inner-city infants were interviewed at each prenatal clinic visit regarding their use of alcohol during pregnancy. Infants were assessed for physical growth and cognitive development repeatedly through age 13 months. In analyses run separately for the infants of younger and older mothers, alcohol-related deficits were seen most strongly in the offspring of women over 30 years of age. This pattern was not caused by lower levels of drinking by the younger mothers. Age-related increases in maternal body fat-to-water ratio and a faster rate of alcohol metabolism in chronic drinking women may account for the greater vulnerability of the offspring of the older mothers. These data suggest that physiological changes associated with aging and/or chronic drinking may play an important role in the alcohol-related birth defects seen in infants exposed at moderate-to-heavy levels.

The relationship between hemodialysis (HD) symptoms and dialyzer membrane composition and area, blood-flow, treatment duration, urea removal, ultrafiltration volume, leukocyte activation, and complement generation (C3a) was studied in 20 patients undergoing 234 HD treatments by 12 different modes in random order using Cuprophan, hemophane, or polyamide membranes with small or large membrane areas with high Qb (400 ml/min) and short duration (2 h) or low Qb (200 ml/min) and long duration (4 h). Fewer symptoms occurred during the 2-h HD at high Qb than during the 4-h HD with low Qb (19% vs. 32%, p = 0.0351). No differences were observed between different dialyzer membranes or areas. More intradialytic symptoms occurred when urea elimination was high than it was low (p = 0.0044). Leukocyte activation (leukocyte drop) after 15 min of dialysis and complement generation did not influence symptom incidence. Blood pressure changes were mainly influenced by ultrafiltration volume (p < 0.001). Symptoms between dialyses were determined by urea removal and ultrafiltration. Membrane, area, or Qb were of no importance. Thus, duration of dialysis, urea removal, and demand for ultrafiltration, but not membrane composition, area, or biocompatability, are important for the development of HD-related symptoms.

Fetal alcohol exposure is associated with slower reaction times (RTs) in children, suggesting an alcohol-related deficit in "speed of central processing." This study examined effects of prenatal alcohol exposure on a new paradigm which, for the first time, directly assesses RT in infancy. RT was assessed in 103 Black, inner-city, 6.5-month-olds born to women recruited prenatally based on alcohol consumption during pregnancy. Maternal drinking was related to longer RTs and to fewer fast responses, after controlling for potential confounders. The incidence of fast performance was reduced in infants whose mothers averaged at least 0.5 oz absolute alcohol/day, indicating an impact at lower levels than those associated with fetal alcohol syndrome. The RT deficits were dose-dependent and not attributable to maternal depression, intellectual stimulation, prenatal drug exposure, or postpartum maternal drinking. This study provides the first evidence of an alcohol-related RT deficit in infancy.

The efficacy of alcohol screening questionnaires, the TWEAK, T-ACE, NET, MAST, and CAGE, in detecting periconceptional risk-drinking, > or = 1 oz absolute alcohol/day, was investigated in 4743 African-American women attending an inner-city prenatal clinic who had reported ever drinking. Sensitivity, specificity, positive predictive value, efficiency, follow-up rates, and receiver operating characteristics of the questionnaires were examined to compare the overall effectiveness of the questionnaires and their performance at cut-points defining positive scores ranging from 1 to 3. Relatively little difference between TWEAK, T-ACE, and MAST was seen in the receiver operating characteristic accuracy indices; NET and CAGE lagged behind. Sensitivity/specificity scores for the two questionnaires most sensitive at cut-point 1 were TWEAK (87/72) and T-ACE (83/75). At cut-point 2, sensitivity was optimized with respect to specificity; TWEAK (79/83) was significantly more sensitive than T-ACE (70/85; p = 0.002). At cut-point 3, the two most sensitive tests were MAST (61/92) and TWEAK (59/94). In general, measures of merit were not greatly affected by the time between conception and the administration of the screens. Screening was most sensitive for women interviewed during the first 15 weeks of pregnancy; risk-drinkers tended to delay entry into prenatal care, increasing positive predictive values associated with screening later in pregnancy. This study confirms the utility, when screening for risk-drinking during pregnancy, of brief questionnaires that assess alcohol intake indirectly by asking women about their tolerance to alcohol's effects, psychological consequences of drinking, and significant others' concern about their drinking. It validates T-ACE and provides preliminary data indicating that TWEAK may outperform T-ACE.

The association of fetal growth retardation with prenatal exposure to alcohol, smoking, opiates, and cocaine is well documented, but relatively little is known about the effects of these exposures on postpartum growth. This study assessed physical growth from birth through 6.5 and 13 months in 412 black, inner-city infants recruited on the basis of their mothers' use of alcohol and/or cocaine during pregnancy. Prenatal alcohol exposure was associated with a slower rate of growth during the first 6.5 postpartum months. This postnatal growth retardation was associated with maternal drinking during a critical period--the latter part of gestation--and was not related to drinking at the time of conception or to postnatal exposure to alcohol from breast-feeding. By contrast, smoking and cocaine use during pregnancy were associated with faster postnatal weight gain. Although maternal smoking was correlated with shorter stature at 6.5 and 13 months, this effect was attributable to maternal drinking during pregnancy, suggesting that the association of maternal smoking with shorter childhood stature reported elsewhere may be due to prenatal alcohol exposure, which was not controlled in prior studies.