Platelet factor 4/heparin antibodies in blood bank donors

Platelet factor 4 (PF4)/heparin antibody, typically associated with heparin therapy, is reported in some heparin-naive people. Seroprevalence in the general population, however, remains unclear. We prospectively evaluated PF4/heparin antibody in approximately 4,000 blood bank donors using a commercial enzyme-linked immunosorbent assay for initial and then repeated (confirmatory) testing. Antibody was detected initially in 249 (6.6%; 95% confidence interval [CI], 5.8%-7.4%) of 3,795 donors and repeatedly in 163 (4.3%; 95% CI, 3.7%-5.0%) of 3,789 evaluable donors. "Unconfirmed" positives were mostly (93%) low positives (optical density [OD] = 0.40-0.59). Of 163 repeatedly positive samples, 116 (71.2%) were low positives, and 124 (76.1%) exhibited heparin-dependent binding. Predominant isotypes of intermediate to high seropositive samples (OD >0.6) were IgG (20/39 [51%]), IgM (9/39 [23%]), and indeterminate (10/39 [26%]). The marked background seroprevalence of PF4/heparin antibody (4.3%-6.6%) with the preponderance of low (and frequently nonreproducible) positives in blood donors suggests the need for further assay calibration, categorization of antibody level, and studies evaluating clinical relevance of "naturally occurring" PF4/heparin antibodies.     

Transcranial direct current stimulation and constraint-induced therapy in cerebral palsy: A randomized,blinded, sham-controlled clinical trial

We investigated the safety, feasibility, and efficacy of transcranial direct current stimulation (tDCS) combined with constraint-induced movement therapy (CIMT) in children and young adults with unilateral cerebral palsy. Twenty participants were randomized to receive active or sham tDCS. The intervention consisted of 10 consecutive weekday sessions of tDCS applied to the non-lesioned hemisphere (20 min) concurrently with CIMT (120 min). Participants, caregivers, and interventionists were blinded to group assignment. The primary safety outcome investigated adverse events. The primary behavioral outcome was the Assisting Hand Assessment. All 20 participants (mean age = 12.7 yrs, range = 7.4–21.6 years) were evaluated for the primary outcomes. No serious adverse events occurred, and the most commonly reported minor adverse events were headache and itchiness. Both groups demonstrated a significant improvement in hand function after the intervention, although no significant effect of tDCS was observed (between-group difference = ?2.18, 95% CI = [?6.48, 2.12], p = 0.30). Although hand function improved overall, no significant differences between intervention groups were found. Children with preserved corticospinal tract circuitry from the lesioned hemisphere, compared to those without, showed greater improvement in hand function (mean difference = 3.04, 95% CI = [?0.64, 6.72], p = 0.099). Our study demonstrates the safety and feasibility of serial sessions of tDCS, and presents preliminary evidence for the effect of CST circuitry on outcomes following tDCS/CIMT. Future work in children with unilateral cerebral palsy should focus on the optimal dosing and consider individual brain circuitry when describing response to combined interventions.

Fundamental Causes of Colorectal Cancer Mortality in the United States: Understanding the Importance of Socioeconomic Status in Creating Inequality in Mortality

Objectives. We used the fundamental cause hypothesis as a framework for understanding the creation of health disparities in colorectal cancer mortality in the United States from 1968 to 2005.Methods. We used negative binomial regression to analyze trends in county-level gender-, race-, and age-adjusted colorectal cancer mortality rates among individuals aged 35 years or older.Results. Prior to 1980, there was a stable gradient in colorectal cancer mortality, with people living in counties of higher socioeconomic status (SES) being at greater risk than people living in lower SES counties. Beginning in 1980, this gradient began to narrow and then reversed as people living in higher SES counties experienced greater reductions in colorectal cancer mortality than those in lower SES counties.Conclusions. Our findings support the fundamental cause hypothesis: once knowledge about prevention and treatment of colorectal cancer became available, social and economic resources became increasingly important in influencing mortality rates.Colorectal cancer is the third leading cause of cancer-related deaths among men and women in the United States.1 In 2010 an estimated 142 570 people in the United States were diagnosed with colorectal cancer, and 50 370 people died as a result of the disease in the same year.2 Over the past 30 years, there have been significant advances in the prevention of colorectal cancer, with reductions in mortality rates due predominantly to improvements in screening and early cancer detection.One of the primary goals of colorectal cancer screening is to reduce mortality by promoting early detection of the disease. Methods used to detect colorectal cancer also aid physicians in the identification and removal of adenomas, which can give rise to colorectal cancer.3 However, because of the unequal distribution of social and economic resources in our society, knowledge about prevention and access to treatments for colorectal cancer is not universal but, rather, is unevenly distributed along the typical social cleavages of race, class, and gender. Thus, social inequalities in colorectal cancer outcomes remain remarkably evident even in an era of successful prevention and treatment strategies.4To gain a more thorough understanding of how existing social inequalities have slowed the decline in mortality attributable to colorectal cancer, we used the “fundamental cause” hypothesis to analyze almost 40 years of US death certificate data. This theoretical construct, first put forth by Link and Phelan,5 stems from the observation that adverse social conditions are repeatedly associated with higher levels of mortality in distinctly different eras and settings.5–9 According to the hypothesis, the association between socioeconomic status (SES) and mortality endures because access to resources such as knowledge, money, power, prestige, and beneficial social connections influences the extent to which people are able to avoid disease and death as well as harness protective factors that can be used to reduce morbidity and mortality.The fundamental cause hypothesis further predicts that as individuals learn how to better prevent or treat diseases, benefits stemming from these newfound abilities will not be distributed uniformly throughout a population. Instead, they will be realized to a greater extent by those who are less likely to face discrimination and stigma and are more likely to have access to socioeconomic resources such as education, money, and information,7 thus resulting in health disparities along common social divisions such as SES and race. According to the hypothesis, more advantaged individuals, relative to their less advantaged counterparts, are poised to disproportionately gain from new health-enhancing capabilities, which may translate to earlier and more rapid reductions in mortality rates.We examined SES inequalities in colorectal cancer mortality in light of major advances in preventing or delaying death, advances predominantly due to improvements in screening and associated policy recommendations. Although colorectal cancer has been surgically treated for more than a century, an emphasis on the prevention of colorectal cancer through widespread screening has become routine only in the past 30 years. In July 1980, the American Cancer Society (ACS) first published recommendations for colorectal cancer screening.10 In 1997, the US Multi-Society Task Force (MSTF), assembled by the US Agency for Health Care Policy Research in conjunction with the American Gastroenterological Association, published its first guidelines for screening for colorectal cancer.11The MSTF guidelines recommended that everyone with risk factors such as age (≥ 50 years), family or personal history of colorectal cancer, history of inflammatory bowel disease, chronic ulcerative colitis, adenomatous polyposis, juvenile polyposis, and hereditary nonpolyposis colorectal cancer be screened. Furthermore, following a positive screen, physicians should conduct a diagnostic evaluation of the colon and rectum, use recommended treatments (including the removal of adenomatous polyps), and consider follow-up surveillance after treatment. In 1997, influenced by MSTF’s recommendations, ACS revised its 1980 guidelines to include recommendations stratified by level of risk of developing colorectal cancer.11 Since then, both ACS and MSTF have issued updates on a regular basis.12The 1997 ACS guidelines recommended that all individuals at an average level of risk begin colorectal cancer screening at the age of 50 years. Individuals at moderate risk, based on a personal or family diagnosis of gastrointestinal adenomatous polyps or colorectal cancer, were recommended to initiate screening at the time of onset, the age of 40 years, or 10 years before the youngest case in the family, whichever was earlier. High-risk individuals with hereditary predispositions to colorectal cancer or a personal diagnosis of inflammatory bowel disease were recommended to initiate screening at puberty, at the age of 21 years, or 8 to 15 years after the onset of inflammatory bowel disease, depending on their individual risk factors.11According to the fundamental cause hypothesis, developments in colorectal cancer screening, such as clearly stated, evidence-based guidelines and their widespread dissemination, will benefit people of high SES more than their low-SES counterparts, thereby creating new health disparities or exacerbating existing disparities over time. Specifically, we expected individuals living in high-SES locales to benefit from recent developments in colorectal cancer screening, beginning with the release of the first colorectal cancer screening recommendations by ACS. Furthermore, given that socioeconomic inequalities are reproduced and often accentuated over time, we expected the association between SES and colorectal cancer mortality to increase over time.     

Comparison of the abilities of synthetic and platelet-derived membranes to enhance thrombin formation

The relative abilities of platelet-derived membranes and synthetic phospholipid vesicles to enhance the prothrombinase-catalyzed conversion of prothrombin to thrombin have been determined. For each type of membrane, the maximum amount of thrombin formed as a function of amount of available lipid was measured using a chromogenic substrate assay. The lipid concentration at which the amount of thrombin formed began to exceed that formed in the absence of lipid (critical phospholipid concentration) was used to compare the surfaces′ abilities to support thrombin formation. For platelet derived membranes and for equimolar, charged-lipid/phosphatidylcholine (PC) vesicles, the critical concentrations increased in the following order: platelet-derived membranes phosphatidylserine (PS) phosphatidic acid (PA) « monomethyl PA and monoethyl PA « phosphatidylinositol and phosphatidylglycerol. For mixed anionic/ neutral lipid vesicles above their phase transitions, measured critical concentrations were relatively insensitive to changes in lipid acyl chains, the neutral lipid component, and membrane curvature but were sensitive to changes in the anionic lipid content of the mixtures. Comparison of these data suggested that equimolar PS/PC and PA/PC vesicles can emulate reasonably well the thrombin-generating ability of platelet-derived membranes.     

Memory and depression in Parkinson's disease

Disorders of learning and memory are a frequent finding in nondemented Parkinson disease (PD) patients. It is not clear to what extent depression, present in at least half the cases of PD, contributes to these disorders. This paper investigates the possible influence of depression on tests of episodic memory in patients with Parkinson's disease (PD). We studied three groups of 11 subjects each (controls, non-depressed PD, mildly to moderately depressed PD). Neuropsychological tests included tests of short and long-term memory in verbal and non-verbal modalities. The two groups of PD patients performed significantly worse than controls on the memory tests, but there were no differences between the depressed and non-depressed PD patients. This lack of influence of depression on neuropsychological performance is compatible with Starkstein's view that cognitive imnpairment is only found beyond a given threshold of depression severity.     

EEG mapping of left hemisphere dysfunction during motor performance in schizophrenia

With a newly developed system of brain electrical activity mapping we studied 10 right-handed, neuroleptic-treated schizophrenics (five of the disorganized, five of the paranoid type, corresponding to 295.1 and .3 in DSM-III), compared with 10 normal controls. Increasingly complex motor tasks were used for cortical activation, all functional states being referenced to resting states recorded after a special relaxation program. We found higher delta and theta amplitudes during rest, as noted in previous studies, and lower beta power values. As a major result, however, we found a widespread left hemisphere dysfunction in schizophrenics, predominantly in the left primary sensory and motor areas. Additionally, we found signs of a "compensatory" overactivation in patients in motor tasks, when this hemisphere is not "used" by normal persons. The results support our findings obtained with this method during multisensory motor coordination in schizophrenia. The results in these patients suggest that these are not merely vigilance, attention, or motivation dysfunctions, but rather specific cortical correlates of impaired motor performance.