John D. Arnold

Retinal and Cerebral Microembolization During Coronary Artery Bypass Surgery A Randomized, Controlled Trial

Background— We sought to compare the effects on ophthalmic function of coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) and off-pump (OPCAB) grafting and to investigate whether retinal microvascular damage is associated with markers of cerebral injury. Methods and Results— Retinal microvascular damage was assessed by fluorescein angiography and color fundus photography. Ophthalmic function was tested by the logarithm of the minimum angle of resolution visual acuity (VA), and cerebral injury, by transcranial Doppler ultrasound–detected emboli and S100 protein values. Twenty patients were randomized. Fluorescein angiography and postoperative VA could not be obtained for 1 CABG-CPB patient. Retinal microvascular damage was detected in 5 of 9 CABG-CPB but in none of 10 OPCAB patients (risk difference, 55%; 95% confidence interval [CI], 23% to 88%; P=0.01). Color fundus photography detected microvascular damage in 1 CABG-CPB patient but in no OPCAB patients; this lesion was associated with a field defect, which remained after 3 months of follow-up. There was no difference in postoperative VA. Doppler high-intensity transient signals (HITS) were 20.3 times more frequent in the CABG-CPB than in the OPCAB group (95% CI, 9.1 to 45; P<0.0001). Protein S100 levels were higher in the CABG-CPB than in the OPCAB group 1 hour after surgery (P<0.001). HITS were 14.7 times more frequent (95% CI, 3.5 to 62; P=0.001) and S100 level 2.1 times higher (95% CI, 1.3 to 3.5; P=0.005) when retinal microvascular damage was present. Conclusions— The relative frequency of retinal microvascular damage between groups shows the extent to which the risk of cerebral injury is reduced with OPCAB. Imaging of part of the cerebral circulation provides evidence to validate markers of cerebral injury.

Retinal and cerebral microembolisation during coronary artery bypass surgery: a randomised controlled trial

Background— We sought to compare the effects on ophthalmic function of coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) and off-pump (OPCAB) grafting and to investigate whether retinal microvascular damage is associated with markers of cerebral injury. Methods and Results— Retinal microvascular damage was assessed by fluorescein angiography and color fundus photography. Ophthalmic function was tested by the logarithm of the minimum angle of resolution visual acuity (VA), and cerebral injury, by transcranial Doppler ultrasound–detected emboli and S100 protein values. Twenty patients were randomized. Fluorescein angiography and postoperative VA could not be obtained for 1 CABG-CPB patient. Retinal microvascular damage was detected in 5 of 9 CABG-CPB but in none of 10 OPCAB patients (risk difference, 55%; 95% confidence interval [CI], 23% to 88%; P=0.01). Color fundus photography detected microvascular damage in 1 CABG-CPB patient but in no OPCAB patients; this lesion was associated with a field defect, which remained after 3 months of follow-up. There was no difference in postoperative VA. Doppler high-intensity transient signals (HITS) were 20.3 times more frequent in the CABG-CPB than in the OPCAB group (95% CI, 9.1 to 45; P<0.0001). Protein S100 levels were higher in the CABG-CPB than in the OPCAB group 1 hour after surgery (P<0.001). HITS were 14.7 times more frequent (95% CI, 3.5 to 62; P=0.001) and S100 level 2.1 times higher (95% CI, 1.3 to 3.5; P=0.005) when retinal microvascular damage was present. Conclusions— The relative frequency of retinal microvascular damage between groups shows the extent to which the risk of cerebral injury is reduced with OPCAB. Imaging of part of the cerebral circulation provides evidence to validate markers of cerebral injury.

Induced primaquine resistance in vivax malaria

Abstract 1. 1) After 36 sequential subinoculations with suboptimal treatment of a single strain of vivax malaria, it has been possible to show a significant increase in trophozoite resistance to primaquine. In fact this resistance reached the point where maximum tolerated doses of primaquine had no action on parasitaemia and fever. This constitutes the maximum resistance that can be achieved in human volunteers. 2. 2) During this programme gametocytes were observed to form and were transmitted through mosquitoes to the stage of mature and apparently viable sporozoites. These failed to infect man. 3. 3) This induced resistance to primaquine should be one additional reason for always using primaquine in conjunction with a good blood schizontocide.

Etodolac, aspirin, and gastrointestinal microbleeding

The effects of etodolac, a new nonsteroidal anti‐inflammatory drug, on gastrointestinal (GI) microbleeding were quantitatively assessed in two studies in healthy adult men. The first was a two‐group, open‐label, parallel comparison of etodolac, 600 mg/day, aspirin, 2600 mglday, and placebo in 20 subjects; the second was a four‐group, double‐blind, parallel comparison of etodolac, 600, 800, and 1200 mglday, aspirin, 2600 mg/day, and placebo in 41 subjects. Subjects in both studies received a single‐blind placebo on days 1 through 7, either etodolac or aspirin on days 8 through 14, and a single‐blind placebo on days 15 through 19. GI blood loss (milliliters per day) was estimated by the radiolabeled (51Cr) erythrocyte method and was based on daily radioactivity counts of stool specimens and regression‐estimated daily blood radioactivity. Etodolac, 600 mglday, induced no significant GI blood loss at any time during the experiments, nor was there significant blood loss after 800 and 1200 mg/day in experiment 2. Blood loss was noted after aspirin in both.

Protein-protein interaction at the air-water interface☆

Abstract A method of measuring the interaction between a protein monofilm and a soluble protein in the subsolution is described. This is measured in terms of monofilm expansion at constant pressure. Soluble proteins will collect at an interface with the formation of a monolayer. At certain higher concentrations, these soluble proteins will invade and expand their own monofilm. This spontaneous protein film expansion occurring in a monofilm on a subsolution of the same protein has been compared with the film expansion observed between dissimilar proteins in the monolayer and in the subsolution. We believe that this comparison of monofilm expansion rates demonstrates the existence of a specific protein-protein interaction and is related to differences in molecular structure. Protein interaction was shown to occur between pork insulin monofilm and alpha globulin reactant at compression pressures between 4.5 dyne-cm. to 16 dyne-cm. (collapse pressure of insulin). The specific expansion observed followed a first-order law. Further, the specific interaction between insulin monofilm and porcine albumin occurred at pH 7.4 and pH 5.1, but not at pH 2.2. Confirmation for this pH dependence was obtained from the pressure-area isotherm studies of equiweight binary mixtures of albumin and insulin.

GLOMERULAR EXTRINSIC MEMBRANOUS DEPOSIT WITH THE NEPHROTIC SYNDROME

The increasing use of serial renal biopsies in clinical medicine presents an unusual opportunity to study the ground substance of the glomerulus and to correlate morphologic and clinical changes. The presence of proteinuria and, frequently, of the nephrotic syndrome provides a means of selecting patients with potential lesions of the ground substance. The most striking lesion of the ground substance seen in this study of the glomerulus is the extrinsic membranous deposit (EMD). This lesion consists of basement membrane changes with diiiuse accumulations of protein material that distort the epithelial cell. A membranous lesion of this type described by Jones,lV2 who used light microscopy, was classified as a form of chronic glomerulonephritis. Churg and Grishman3 interpreted the lesion as the result of the proteinuria and not specifically pathognomonic of a disease entity? FarquharP and Movat and McGregor6 added electron-microscopy findings, but classified their cases as an adult form of l ip id nephrosis. In our series of 187 biopsies with successful electron microscopy in 74 per cent, 6 cases of EMD were diagnosed. We believe that the EMD and its associated clinical findings are a special subgroup of the nephrotic syndrome and that it is probably closely related to, or a variant of, systemic lupus.

Human Subjects in Clinical Research — A Report of Three Studies

THE search for new drugs and technics of medical care requires that man be the final experimental animal. The safeguards for volunteers have thus far assumed two forms. The first has been formal re...

A simple apparatus for measurement of protein monofilm expansion at air-water interface in response to soluble reactants in the subsolution

Abstract A new apparatus and technique for the study of the reaction of macromolecules at the air-water interface with soluble substances in the subsolution is described. A system of piston oils and plastic float with mercury seals is employed to monitor the monofilm area changes at constant pressure. The reaction trays are milled from Teflon, which permits easy instrumentation and cleaning. The test monofilm is compressed to a predetermined pressure by a “piston oil” and is allowed to expand against the oil area on injection of a suitable reactant. The film expansion is isobaric owing to the unique characteristic of the piston oil. A plastic float with mercury seals divides the piston oil area from the test monofilm, and responds to small pressure changes in the latter by an appropriate displacement.

Clinical Use of the Percutaneous Renal Biopsy

The renal biopsy is undoubtedly a justifiable diagnostic tool though it has not yet reached full maturity in clinical practice. Risks. For most patients the risks do not appear to be excessive. An added caution must be exercised in malignant hypertension but even here after careful appraisal of this added risk the biopsy may still be justified. The experience of the operator would appear to modify some of the risk. Returns. The biopsy has often added to the confusion surrounding a given case because it may be uninterpretable or because it provides an unfamiliar complex of findings. Thisresult is becoming less common with increasing experience. Even when the histology of the kidney is not diagnostic, it may suggest something of clinical value about the nature of the disease process, such as the presence of vascular disease, focal nephritis, or tubular disease of unidentified nature. The use of the electron microscope has extended the range of the percutaneous biopsy considerably. It is unfortunate that the cost and complexity of this instrument have confined it to certain centers. It should be remembered also that a number of technical failures will occur, and the sampling error may be large. Despite these real problems, the percutaneous renal biopsy is often the only way of establishing a diagnosis and makes its greatest contribution in the appraisal of the asymptomatic patient with proteinuria and an abnormal urinary sediment.

Chemical agents effective in mediating control of growth and division synchrony of Plasmodium berghei in pinealectomized mice.

Pinealectomy abolishes the growth and division synchrony of Plasmodium berghei which is normally augmented by the photoperiodic rhythm. The augmented synchrony typical of the intact animal may be restored by ubiquinone, members of the vitamin K series, or partly by alpha-tocopherol. This restoration of growth and division synchrony by the 1,4-quinones or the 6-chromanols requires the continued exposure of the pinealectomized animal to the appropriate photoperiodic rhythm. Diets deficient in vitamin K or vitamin E will have the same effect on growth and division synchrony as does pinealectomy. The vascular release of mature schizonts, which is also under the control of the pineal, is only partially restored by the 1,4-quinones, or 6-chromanols. Pinealectomy can be shown to abolish the effects of photoperiodism in augmenting growth and division synchrony of Plasmodium berghei in the mouse (Arnold et al., 1969b). In addition, pinealectomy changes the pattern of mature schizont sequestration of the same infection in mice. The mechanism by which the pineal is activated is not yet known, nor is the mechanism known by which the pineal carries out its part in regulating growth and division synchrony. Similar uncertainties apply to the means by which the pineal regulates vascular capture and release of mature schizonts. It seems likely that the pineal is the junction point for a neural pathway and a chemical pathway. In studying the nature of the pineal as a chemical transducer, we have explored the role of several known chemical agents