Cognitive functioning in patients with suspected chronic toxic encephalopathy: evidence for neuropsychological disturbances after controlling for insufficient effort.

OBJECTIVES: Chronic toxic encephalopathy (CTE) caused by long term occupational exposure to organic solvents is still a controversial disorder. Neuropsychological testing is the cornerstone for diagnosing the syndrome, but can be negatively influenced by motivational problems. In this nationwide study, we investigated the neuropsychological functioning and psychological symptoms of a large group of patients with suspected CTE, and ruled out alternative explanations for their complaints, including suboptimal performance due to insufficient effort. METHODS: We studied participants with suspected CTE (n = 386) who were referred for further diagnosis to the Netherlands Centre of Occupational Diseases in the period 1998-2003 and who had completed the entire diagnostic protocol. Patients were excluded if there was the slightest suspicion that test performance had been negatively influenced by insufficient effort (n = 221), or if comprehensive assessment identified an alternative diagnosis (n = 80). Insufficient effort was defined by a combination of three indices. The neuropsychological test scores of the patient group (n = 85) were compared with those of a control group of building trade workers matched for sex, age, and educational level (n = 35). RESULTS: The patient group had significantly more psychological complaints and performed significantly worse than the control group on tests of speed of information processing and memory and learning. However, only a small percentage of the patients had clearly abnormal scores for cognitive speed (9%) or memory (8%). Attention, verbal abilities, and constructional functions were not disturbed. Exposure duration and cognitive complaints were significantly correlated, whereas the correlation between exposure duration and neuropsychological domain scores was not significant. CONCLUSIONS: Insufficient effort was present in a substantial part of the patient group. After minimising the likelihood that insufficient effort negatively influenced neuropsychological scores, we still found neuropsychological deficits in speed of cognitive processing and memory; however, these scores were clearly abnormal only in a minority of patients with suspected CTE. Screening instruments should focus on these domains.

Specific removal of anti-A and anti-B antibodies by using modified dialysis filters.

Removal of anti-A and anti-B blood group antibodies from human blood has been shown to facilitate cross-matched kidney transplantation by preventing hyperacute rejection. Patients in these studies had anti-A and anti-B antibodies removed by using plasmapheresis, followed by immunoadsorption onto packed bead columns. We conducted a study to assess the feasibility of selectively removing anti-A and anti-B antibodies directly from blood by using modified dialysis filters. An anti-A and anti-B specific antigen was covalently attached to the lumenal surfaces of hollow fibers within selected commercial dialysis modules. The filters were able to reduce the anti-A and anti-B titers of 300 ml of blood to 2 or below. A low molecular weight fraction of our antigen system was found to have no antibody binding capacity. The standard antigen was purified by removal of the low molecular weight fraction and a dialysis filter was modified by using the purified antigen. This filter displayed a six-fold higher capacity than a dialysis filter modified with the same mass of standard antigen. We conclude that selective blood group antibody removal by antigen modified dialysis filters is feasible and may be a simpler system than plasmapheresis followed by immunoadsorption.

Validation of a model for flow-dependent carbon dioxide exchange in artificial lungs.

The exchange rate of CO2 in artificial lungs depends on the sweep gas flow rate. Control of the amount of CO2 removed by an artificial lung requires quantitative knowledge of the flow dependence. A simple model of the dependence of CO2 exchange on sweep gas flow rate in artificial lungs has been previously presented (1). For a given partial pressure of CO2 in the blood phase, sweep gas flow rate, and CO2 exchange rate, the model indicates how close the CO2 exchange rate is to the maximum level attainable by the artificial lung. The focus of this study was to validate the model experimentally by testing 2 commercial artificial lungs in an in vitro test loop. The CO2 exchange rate for each artificial lung was measured over a range of sweep gas flow rates. Linear regression was used to fit the data to the model and estimate the maximum possible CO2 exchange rate and the average water-side PCO2 (PCO2w). The difference between the measured and regressed values of PCO2w was used as an indicator of the ability of the model to quantitatively predict the dependence of CO2 exchange on gas flow rate. This difference was less than 5% for each experiment, indicating that the model can be used to guide control of CO2 exchange rates in artificial lungs.

Development of a low flow resistance intravenous oxygenator.

A potentially attractive support device for patients with acute respiratory failure is an intravenous membrane oxygenator. One problem, however, is that the membrane surface area required for sufficient gas exchange can unduly increase vena caval pressure drop and impede venous return. The purpose of this study was to design and develop an intravenous oxygenator that would offer minimal venous flow resistance in situ. The device uses a constrained fiber bundle of smaller cross sectional size than the vena cava so as to effect an intentional shunt flow of venous blood around the fiber bundle and reduce the venous pressure drop caused by the device. A pulsating balloon within the fiber bundle redirects part of this shunt flow into reciprocating flow in and out of the fiber bundle. This offers dual advantages: 1) Blood flow through the fiber bundle is mainly perpendicular to the fibers; and 2) the requisite energy for driving flow comes largely from the pneumatic system pulsating the balloon, not from a venous pressure drop. In this mode a full length device with a 2 cm fiber bundle in a 2.5 cm blood vessel would offer a pressure drop of only a few millimeters of mercury. The use of constrained fiber bundles requires good uniformity of fiber spacing for effective gas exchange. Several prototypes have been fabricated, and CO2 and O2 exchange rates of up to 402 and 347 ml/min/m2 have been achieved during acute animal implantation.

Recent progress in engineering the Pittsburgh intravenous membrane oxygenator.

The University of Pittsburgh intravenous membrane oxygenator (IMO) is undergoing additional engineering development and characterization. The focus of these efforts is an IMO device that can supply as much as one-half basal O2 consumption and CO2 elimination rates while residing within the inferior and superior vena cavae after peripheral venous insertion. The current IMO design consists of a bundle of hollow fiber membranes potted to manifolds at each end, with an intra-aortic type balloon integrally situated within the fiber bundle. Pulsation of the balloon using helium gas and a balloon pump console promotes fluid and fiber motion and enhances gas exchange. During the past year, more than 15 IMO prototypes have been fabricated and extensively bench tested to characterize O2 gas exchange capacity, balloon inflation/deflation over relevant frequency ranges, and the pneumatics of the sweep gas pathway through the device. The testing has led to several engineering changes, including redesign of the helium and sweep gas pathways within the IMO device. As a result, the maximum rate of balloon pulsation has increased substantially above the previous 70 bpm to 160 bpm, and the vacuum pressure required for sufficient sweep gas flow has been reduced. The recent IMO prototypes have demonstrated an O2 exchange capacity of as much as 90 ml/min/m2 in water, which appears within 70% of our design goal when extrapolated to scaled up devices in blood.

A Dutch family with benign hereditary chorea of early onset: differentiation from Huntington's disease.

A large Dutch family of 88 members, running through five generations, is described with benign hereditary chorea of early onset. The clinical presentation was heterogeneous. The chorea manifested in late infancy or childhood, interfered with writing, was non-disabling, stable or even improved in adulthood in most cases, but was slowly progressive with gait impairment in some. There was mild dysarthria and normal intelligence. EEG brain CT-scanning and MRI were normal. Huntington's disease was excluded by analysis of the I T 15 gene, which showed a normal number of the CAG trinucleotide repeats in two patients. It is concluded that benign hereditary chorea of early onset is an entity different from Huntington's disease and that in cases of early onset chorea the diagnostic accuracy is markedly improved by DNA testing.