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Biomedical subjects

R A Clark

Publications and source records attributed to R A Clark.

At least 343 records · Page 19Linked to original sources

Acute mesenteric ischemia: angiographic spectrum.

Fifty-six patients, selected by clinical criteria, underwent angiography for suspected acute mesenteric ischemia. Twenty-nine patients subsequently did not have mesenteric ischemia and had negative arteriograms. Twenty-seven patients had mesenteric ischemia: arterial thrombosis (three), arterial embolus (seven), venous thrombosis (five), vasculitis with thrombosis (one), and nonocclusive ischemia (11). Of these 27 patients, 12 (44%) received intraarterial vasodilator infusions. Overall, 13 (48%) of the 27 patients survived their hospitalization, including five (45%) of 11 with nonocclusive ischemia. This experience confirms that nonocclusive ischemia is the most common form of the disorder diagnosed by angiography. Most patients with mesenteric ischemia are candidates for intraarterial vasodilator therapy. Early angiography in patients with suspected acute mesenteric ischemia permits early diagnosis and differentiation between occlusive and nonocclusive types. Interventional infusion therapy may improve survival.

Acute Disease↗

A comparison of computed tomography and sonography in choledocholithiasis.

A comparison was made of sonography and computed tomography (CT) for the diagnosis of choledocholithiasis. Sonography correctly diagnosed nine of 49 patients with choledocholithiasis for a sensitivity rate of 18%. The accuracy rate for sonography was 19%; there were five false-positive examinations. CT correctly identified common duct stones in 26 of 30 patients for a sensitivity rate of 87%. The accuracy rate was 84%; there was one false positive. Sonography is limited in its ability to image calculi in the distal common bile duct. CT is effective for imaging common duct stones and is superior to sonography for diagnosing this cause of biliary obstruction.

Diagnosis, Differential↗

Monitoring the iodine dose.

The administration of large amounts of iodinated contrast media can result in acute renal failure. Many diagnostic examinations, including pyelography, computed tomography and digital vascular imaging, require the injection of significant amounts of contrast media. Additionally, these examinations may be performed within 24-48 hours of each other, increasing the likelihood of a dose-induced acute renal failure. To avoid this complication, we have developed and implemented a system to monitor and control the patient's dose of iodine. This system effectively alerts individuals to the iodine dose the patient has received within the last 48 hours. The information is being used to compile a study concerning the relationship between iodine dose and the occurrence of acute renal failure.

Acute Kidney Injury↗

Down-regulation of human natural killer activity against tumors by the neutrophil myeloperoxidase system and hydrogen peroxide.

There is growing evidence that natural killer (NK) cells play an important role in immune surveillance against tumors and certain infections. The coexistence of activated neutrophils with lymphocytes in tumor masses and inflammatory tissues suggests the possibility of interaction between secreted neutrophil products and nearby lymphocytes. We examined the susceptibility of lymphocyte NK activity to oxidative injury by the neutrophil myeloperoxidase (MPO) system and H2O2 with the use of a cellfree model system. Exposure of human mononuclear leukocytes (MNL) to MPO, an H2O2-generating system (glucose + glucose oxidase), and a halide (C1- or I-) resulted in marked suppression of MNL-NK activity, as measured by 51Cr release from K562 tumor targets (p less than 0.001). This suppression was dependent on the presence and activity of each system component and was blocked by azide and catalase, but not by heated catalase. In spite of the marked functional suppression of NK activity, MNL viability was more than 95% and target binding frequency was not affected. NK suppression was reversible after 24 hr in culture. The mechanism of suppression was dependent on the amount and rate of H2O2 delivered, and on MNL number. MPO was essential when H2O2 flux was low or when MNL numbers were high. As H2O2 flux increased or MNL numbers decreased, NK suppression gradually became MPO-independent and was mediated by H2O2 alone. The ability of the MPO system to compromise lymphocyte NK function may explain the in vitro inhibition of NK activity of mixed cell populations by the tumor promoter phorbol esters, because these agents are potent stimulants for neutrophil secretion of MPO and H2O2. This study may also provide a possible mechanism for the reported in situ NK activity suppression by adherent phagocytic cells during carcinogenesis in both humans and animals.

Azides↗

Inherited deficiency of C8 in a patient with recurrent meningococcal infections: further evidence for a dysfunctional C8 molecule and nonlinkage to the HLA system.

An adult male with recurrent meningococcal infections is reported whose serum lacked functional C8 activity but possessed antigenic C8. The addition of 1500 U of purified C8/ml of serum restored hemolytic activity to normal. Four to five times more C8 was required to restore bactericidal activity than to restore hemolytic activity. Bactericidal activity could also be restored by mixing the patient's serum with a second C8-deficient serum that lacked detectable antigenic or functional C8. The patient's serum contained bactericidal antibody for groups A, B, C, and Y meningococci and specific antibody to group Y capsular polysaccharide. There was two to three times more bactericidal antibody activity in the serum than in a pool of normal sera for the infecting strain. Family studies disclosed a sibling who was HLA identical to the patient but whose serum contained normal amounts of total hemolytic and C8 functional activity.

Adolescent↗

CT of liver tumors.

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Adenoma, Bile Duct↗

The cost of initiating appropriate therapy for skin diseases: a comparison of dermatologists and family physicians.

A prospective survey examining how forty-one dermatologists and forty-one family practitioners manage patients with skin diseases was carried out in Atlanta, GA. The results show that dermatologists diagnose more conditions accurately, refer patients less often, charge more in professional fees, prescribe more medicines at higher cost to the patient but order laboratory tests costing less than do family physicians. More appropriate treatment was prescribed for nine of ten diseases by specialists compared to generalists. This limited study provides data which suggests that dermatologists provide more appropriate care than family practitioners in the treatment of skin diseases at no greater cost.

Clinical Laboratory Techniques↗

Subcellular localization of the b-cytochrome component of the human neutrophil microbicidal oxidase: translocation during activation.

We describe a new method for subcellular fractionation of human neutrophils. Neutrophils were disrupted by nitrogen cavitation and the nuclei removed by centrifugation. The postnuclear supernatant was applied on top of a discontinuous Percoll density gradient. Centrifugation for 15 min at 48,000 g resulted in complete separation of plasma membranes, azurophil granules, and specific granules. As determined by ultrastructure and the distribution of biochemical markers of these organelles, approximately 90% of the b-cytochrome in unstimulated cells was recovered from the band containing the specific granules and was shown to be in or tightly associated with the membrane. During stimulation of intact neutrophils with phorbol myristate acetate or the ionophore A23187, we observed translocation of 40-75% of the b-cytochrome to the plasma membrane. The extent of this translocation closely paralleled release of the specific granule marker, vitamin B12-binding protein. These data indicate that the b-cytochrome is in the membrane of the specific granules of unstimulated neutrophils and that stimulus-induced fusion of these granules with the plasma membrane results in a translocation of the cytochrome. Our observations provide a basis for the assembly of the microbicidal oxidase of the human neutrophil.

Calcimycin↗

Human neutrophil elastase does not bind to alpha 1-protease inhibitor that has been exposed to activated human neutrophils.

The effect of leukocyte-derived oxidants on the elastase-inhibitory capacity of alpha 1-protease inhibitor was examined in an in vitro system using cells and purified proteins from human sources. The exposure of alpha 1-protease inhibitor to the myeloperoxidase-hydrogen peroxide-halide system resulted in a nearly complete loss of its ability to bind and inactivate purified human neutrophil elastase. A similar loss of binding to and inactivation of human neutrophil elastase was observed on exposure of alpha 1-protease inhibitor to human neutrophils in the presence of a halide and the neutrophil-activating agent, phorbol myristate acetate. This loss of elastase binding activity was abrogated by the addition of azide or catalase but not superoxide dismutase or heated catalase. The data suggest oxidative inactivation of alpha 1-protease inhibitor by secreted myeloperoxidase and hydrogen peroxide. Thus, the reported effects of leukocyte oxidants, especially the myeloperoxidase system, on alpha 1-protease inhibitor have been confirmed using the most pathophysiologically relevant protease, human neutrophil elastase, as the test enzyme. The role of the neutrophil in the pathogenesis of emphysema may, therefore, include the secretion of both elastase and oxidants that impair antielastase defenses.

Blood Proteins↗

CT differentiation of subphrenic abscess and pleural effusion.

The computed tomographic scans of 38 patients with proven subphrenic abscesses and 28 patients with proven pleural effusions were reviewed without knowledge of the final diagnosis. In 26% of cases the hemidiaphragm could be identified directly as a stripe, while in 71% of cases only the hemidiaphragmatic contour could be seen. In 3% of cases the hemidiaphragm position was indeterminate because insufficient scans of the chest or abdomen were obtained. In the cases where the hemidiaphragm position could be established, the computed tomographic diagnosis was correct in 100% of subphrenic abscesses and in 96% of pleural effusions. Methods of identifying the hemidiaphragm on computed tomography and the possible pitfalls are discussed.

Diagnosis, Differential↗