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Biomedical subjects

R A Clark

Publications and source records attributed to R A Clark.

At least 379 records · Page 21Linked to original sources

Pancreatic gas: indication of pancreatic fistula.

Although pancreatic gas may be associated with pancreatic abscess, it was found that pancreatic gas indicates the presence of a fistula rather than abscess alone. Of 10 patients with pancreatic gas on computed tomography, fistulas were present in all. Fistulization results from pancreatic pseudocyst rupture or as a complication of phlegmonous pancreatitis. In most cases the fistula does not adequately decompress the pseudocyst or pancreatic phlegmon. In addition, fistulas may predispose to sepsis and hemorrhage. It is important to identify the presence of a pancreatic fistula since patient management may be altered.

Abscess↗

Chemotactic factor inactivation by stimulated human neutrophils mediated by myeloperoxidase-catalyzed methionine oxidation.

Leukocyte chemoattractants were inactivated when exposed to human neutrophils and either ingestible particles or phorbol esters. Loss of biologic activity was time- and temperature-dependent, required physiologic concentrations of viable neutrophils and a halide, and was inhibited by azide or catalase. Neutrophils from patients with either hereditary myeloperoxidase deficiency or chronic granulomatous disease failed to inactivate the chemoattractants unless purified myeloperoxidase or H2O2, respectively, was added. Susceptibility to inactivation by neutrophils correlated with the presence of methionine in the attractant. Loss of chemotactic activity was blocked by low concentrations of methionine and by higher concentrations of other reducing agents, but was unaffected by oxidized methionine. Paper chromatography demonstrated that exposure of a formyl-methionyl peptide chemotactic factor to either the cellfree myeloperoxidase system or stimulated neutrophils resulted in its conversion to a molecular species whose location in the chromatographs was identical to that of the peptide containing oxidized methionine. Thus, stimulated human neutrophils inactivate peptide chemoattractants by secretion of myeloperoxidase and H2O2, which combine with halides to form oxidants that react with a critical methionine residue. We suggest that myeloperoxidase-catalyzed oxidation of thioethers may constitute an inflammatory control mechanism as well as a general means of modifying the functional properties of biologic mediators.

Aminopeptidases↗

Immunofluorescent staining with antibodies to factor VIII, fibronectin, and collagenous basement membrane protein in normal human skin and port wine stains.

Specific antibodies directed against three important components of the vessel wall (collagenous basement membrane protein-type IV collagen, fibronectin, and factor VIII) were used to study and compare the distribution of these proteins in normal skin and port wine stains. Collagenous basement membrane protein was localized to the basement membrane and basal lamina zones of blood vessels, appendages, arrector pili muscles, endoneurium and perineurium, and the dermoepidermal junction of both port wine stains and normal skin. Vessels of the port wine stain as well as those of normal skin showed a similar narrow uniform homogeneous line of fluorescence. Granular endothelial staining was seen in the blood vessels of both normal skin and port wine stains. The distribution of fibronectin was that of a low-intensity punctate pattern situated in the subendothelial region of both port wine stain and normal vessels and in the basement membrane zones of hair follicles, endoneurium and perineurium, and the dermoepidermal junction.

Adolescent↗

0.1% triamcinolone acetonide ointment and patch test responses.

The effect of topical steroids on patch test responsiveness was investigated in 15 subjects. A 0.1% triamcinolone acetonide ointment and a control preparation were applied three times daily to opposing sites on the upper part of the inner arms prior to patch testing. From a total of 18 pairs of patch tests applied to the 15 patients, substantial differences in the paired reactions were seen in only three patients after 96 hours. Of these, two had the more intense reaction on the control side, and the third had a greater reaction on the triamcinolone-pretreated side. Previously applied, intermediate-strength topical steroids are unlikely to prevent the detection of contact allergy by patch testing.

Dermatitis, Contact↗

Left subclavian arteriography via the translumbar approach.

Selective left subclavian arteriography and thoracic aortography were performed via the translumbar approach. The resultant studies were technically and diagnostically satisfactory. This approach can be used when the femoral and axillary arteries are not available for vascular access.

Aorta, Thoracic↗

Fibronectin fragment(s) are chemotactic for human peripheral blood monocytes.

Both plasma-derived and cell-derived fibronectin are deposited at sites of inflammation and wound healing and are associated with migrating cell populations including monocytes/macrophages. We found that fibronectin fragments generated by endogenous protease(s) are potent chemoattractants for human peripheral blood monocytes, whereas intact fibronectin has no activity. Fibronectin preparations produced by gelatin affinity chromatography in the absence of protease inhibitors contained 90 to 220 kd fragments and had potent chemotactic and chemokinetic activity for monocytes but no activity for human neutrophils or lymphocytes. The addition of phenylmethylsulfonyl fluoride to plasma reduced but did not eliminate the recovery of fibronectin fragments and likewise reduced the chemotactic activity. When the preparations were further purified by DEAE ion exchange and Sepharose 4B molecular sieve chromatography, however, intact fibronectin was recovered that lacked both chemotactic and chemokinetic activity. When fragment-poor fibronectin was allowed to sit at 25 degrees C in NaN3 but without protease inhibitors, increased fragmentation and increased chemotactic activity were noted. In addition, chemotactically active small m.w. fragments arose from high m.w. fragments or from intact fibronectin as demonstrated by rechromatography experiments over Sephadex G-150. These findings suggest that proteolytic cleavage of fibronectin during inflammatory processes produces fragments that selectively augment the recruitment of monocytes into tissue sites of inflammation.

Cells, Cultured↗

Chemotactic factors trigger their own oxidative inactivation by human neutrophils.

Human neutrophils exposed to phagocytosable particles or soluble activating agents are able to inactivate chemotactic factors. The present experiments demonstrate that the peptide chemoattractant, f-met-leu-phe, serves as a sufficient secretory stimulus to trigger its own functional inactivation by neutrophils. This phenomenon is dependent on the concentration of the chemoattractant and the duration of its exposure to neutrophils. It requires low numbers of viable neutrophils and physiologic concentrations of chloride and is blocked by addition of azide, cyanide, catalase, or methionine, but not methionine sulfoxide, superoxide dismutase, or heated catalase. Neutrophils from patients with myeloperoxidase deficiency of chronic granulomatous disease are not able to inactivate the chemotactic factor unless purified myeloperoxidase or hydrogen peroxide, respectively, is added. Thus, chemotactic peptides can trigger neutrophils to secrete myeloperoxidase and hydrogen peroxide, which together with a halide destroy the biologic activity of the peptide, probably by oxidizing a methionine residue. These observations support the pathophysiologic significance of oxidative inactivation of humoral mediators as a negative feedback inflammatory control mechanism.

Chemotactic Factors↗

Effects of the myeloperoxidase system on fluorescent probes of granulocyte membrane potential.

Activation of normal or myeloperoxidase-deficient human granulocytes by phorbol myristate acetate resulted in an initial membrane depolarization as indicated by an increase in fluorescence of the lipophilic cation probe of membrane potential, 3,3'-dipropylthiodicarbocyanine. A subsequent apparent hyperpolarization (decrease in fluorescence) was observed in normal but not myeloperoxidase-deficient cells. Addition of purified myeloperoxidase restored a normal pattern of fluorescence changes to the enzyme-deficient granulocytes. The secondary decrease in fluorescence in normal cells was markedly blunted by addition of azide, cyanide, or catalase. In a cell-free system, the fluorescence of 3,3'-dipropylthiodicarbocyanine, but not that of 3,3'-dipentyloxadicarbocyanine, was rapidly eliminated by myeloperoxidase in the presence of hydrogen peroxide and a halide; this loss of fluorescence was inhibited by azide, cyanide, or catalase. These findings indicate that secretion of myeloperoxidase and hydrogen peroxide by activated granulocytes results in decreased fluorescence of 3,3'-dipropylthiodicarbocyanine, probably by thioether oxidation. While the determination of initial rates of depolarization using this probe is unaffected by the myeloperoxidase system, measurement of extent of depolarization and any subsequent membrane potential changes requires the addition of inhibitors. In the absence of inhibitors, the secondary decrease in fluorescence can be used as an indicator of secretion of myeloperoxidase and hydrogen peroxide.

Benzothiazoles↗

Myeloperoxidase-catalyzed inactivation of alpha 1-protease inhibitor by human neutrophils.

We have examined the effect of the myeloperoxidase-hydrogen peroxide-halide system and of activated human neutrophils on the ability of serum alpha 1-protease inhibitor (alpha 1-PI) to bind and inhibit porcine pancreatic elastase. Exposure to the isolated myeloperoxidase system resulted in nearly complete inactivation of alpha 1-PI. Inactivation was rapid (10 to 20 s); required active myeloperoxidase, micromolar concentrations of H2O2 (or glucose oxidase as a peroxide generator), and a halide cofactor (Cl- or I-); and was blocked by azide, cyanide, and catalase. Intact neutrophils similarly inactivated alpha 1-PI over the course of 5 to 10 min. Inactivation required the neutrophils, a halide (Cl-), and a phorbol ester to activate secretory and metabolic activity. It was inhibited by azide, cyanide, and catalase, but not by superoxide dismutase. Neutrophils with absent myeloperoxidase or impaired oxidative metabolism (chronic granulomatous disease) failed to inactivate alpha 1-PI, and these defects were specifically corrected by the addition of myeloperoxidase or H2O2, respectively. Thus, stimulated neutrophils secrete myeloperoxidase and H2O2 which combine with a halide to inactivate alpha 1-PI. We suggest that leukocyte-derived oxidants, especially the myeloperoxidase system, may contribute to proteolytic tissue injury, for example in elastase-induced pulmonary emphysema, by oxidative inactivation of protective antiproteases.

Alpha-Globulins↗

Transcatheter embolization of hepatic arteriovenous fistulas for control of hemobilia.

Two cases of traumatic hemobilia are presented in which hemorrhage was controlled by transcatheter vascular occlusion with stainless steel coils. Embolic therapy was safely performed without liver necrosis, despite the presence of portal hypertension in 1 patient. The technique is a useful alternative to surgery, which did not control hemorrhage in 1 case.

Adult↗

The bronchitic patient: a study of his employment problems.

Ninety-three male chronic bronchitics aged 40-64 years, 41 employed and 52 unemployed, were studied by structural interviews to evaluate factors leading to unemployment. Age was not important. Those employed were a little less disabled, and more were skilled, married, had working wives, had given up smoking, had tolerant employers and had suitable jobs, and fewer had travel problems. Of those unemployed most were not actively seeking work and, in half, income had not fallen with unemployment. Those interviewed felt that the Disablement Resettlement Officer, Industrial Rehabilitation Unit and their trade union did little to help with their problems. Ways to improve employment prospects for bronchitics are discussed.

Adult↗

Acute arterial gastrointestinal hemorrhage: efficacy of transcatheter control.

Sixty-five sites of arterial gastrointestinal hemorrhage in 63 patients were managed with transcatheter therapy. Arterial vasopressin infusion was attempted primarily for all but three sites; embolization was used in these cases and in those for whom vasopressin infusion failed to control bleeding. The results obtained suggest that this regimen, that is, primary vasopressin infusion with embolization reserved for infusion failures or contraindications, is more effective for control of arterial gastrointestinal hemorrhage than the use of either method alone. The role of primary embolization for control of this type of bleeding may need reassessment.

Angiography↗

CT of malignant pleural mesothelioma.

Malignant pleural mesothelioma is a rare tumor. Although the chest film findings of pleural mesothelioma are well described, there are few descriptions of the findings of computed tomography (CT). This report describes the CT findings in five cases of pleural mesothelioma. In each case the CT showed an extensive, irregular, pleural-based mass surrounding the lung, spreading into the fissures, and extending into the mediastinum. In two cases there was also extension into the contralateral chest, and in one case each there was extension into the abdomen and chest wall. In each case the chest radiographs underestimated the extent of disease, when compared to CT. When an irregular, pleural-based mass involving most of the hemithorax is identified on CT, the diagnosis of mesothelioma can be suggested and at the same time the extent of the tumor may be evaluated. This is important because the diagnosis of mesothelioma is difficult and because treatment and prognosis may depend on the extent of the disease.

Aged↗