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Biomedical subjects

J L Seltzer

Publications and source records attributed to J L Seltzer.

At least 55 records · Page 3Linked to original sources

Anaesthetic technique for transvenous pulmonary embolectomy.

Transvenous pulmonary catheter embolectomy is being used as a method of treatment for patients suffering from massive pulmonary embolism. The anaesthetic management of these patients can be complex. Presented is a case of transvenous pulmonary embolectomy in a patient who also had an intravascular volume deficit secondary to haemorrhage and possible reperfusion oedema. A discussion of appropriate monitoring during procedure follows.

Aged↗

Purification of gelatin-specific neutral protease from human skin by conventional and high-performance liquid chromatography.

Human skin, maintained in serum-free organ culture, secretes a neutral metalloendopeptidase which is remarkably specific for gelatin. Because the product peptides from the action of collagenase on collagen become denatured into random coil polypeptides of 25000 and 75000 daltons at physiological temperature, it is thought that this "gelatinase" is the second, and possibly the only other enzyme in the pathway of extracellular collagen degradation. New types of high-performance liquid chromatography (HPLC) columns have enabled us to improve the yields of active gelatinase from skin culture medium. Raw medium, which has been dialyzed and lyophilized, is fractionated with ammonium sulfate, and applied to Pharmacia Blue Sepharose in a batch step. The 0.4 M sodium chloride eluate is then subjected to gel filtration on Sephacryl S-200, followed by gradient elution from Amicon Green Sepharose. The fractions with gelatinolytic activity are applied to a Bio-Rad TSK-Phenyl-5PW HPLC column for mild hydrophobic chromatography with a gradient of decreasing ammonium sulfate concentration. In the final step, the enzyme is applied to a Pharmacia Mono-Q FPLC column and eluted with a gradient of sodium chloride. At this point, the enzyme appears as two bands, corresponding to enzymatic activity zymograms on sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Chromatography, Gel↗

Nitroglycerin-controlled circulation in orthognathic surgery.

Significant blood loss is a potential complication of maxillary osteotomies and maxillary and mandibular osteotomies. Controlling circulation by lowering blood pressure is a technique that has been used successfully to avoid this problem. Of the various agents available, nitroglycerin was chosen because of its known beneficial cardiovascular effects and its lack of toxicity as compared with sodium nitroprusside. Nine patients undergoing either maxillary or maxillary/mandibular osteotomies were anesthetized with halothane, N2O, O2, and supplemental doses of a muscle relaxant and narcotic. Nitroglycerin was used to lower mean arterial pressure during periods of potential increased blood loss. Estimated blood loss was 439 +/- 1.19 ml. The hemoglobin and hematocrit fell slightly from 13.8 +/- 1.74 g/dl and 41.2 +/- 5.11% to 12.04 +/- 1.8 g/dl and 35.6 +/- 4.9%. Attenuation of the pulmonary hypoxic vasoconstriction reflex was also seen, as was evidenced by a decrease in PaO2 after nitroglycerin administration. It was concluded that nitroglycerin is a safe and efficacious agent for controlled circulation during maxillary osteotomy surgery.

Adolescent↗

Isolated regional perfusion; anaesthetic technique, monitoring and blood replacement.

Isolated regional perfusion for the treatment of malignant melanoma is an accepted method of treatment. No standard of anaesthetic practice has been established for those individuals. Perioperative records of patients undergoing isolated limb perfusion were studied to determine adequate blood replacement. Records were examined and compared for (1) age, (2) ASA physical status, (3) presence of associated disease, (4) anaesthetic technique, (5) the amount of blood and fluid replacement, (6) preoperative haemoglobin (hgb) and haematocrit (hct) and postoperative serial complete blood counts. Fifteen patients were studied (mean age 53 +/- 16 yrs). Mean blood and fluid replacement was: packed red blood cells; 2.28 +/- 0.82 units, 722 +/- 17 ml of 5 per cent albumin, 1747 +/- 21 ml crystalloid. There were twelve Physical Status Class I or II and three Class III patients. All patients received general anaesthesia. There was a statistically significant difference in the preoperative and postoperative values for haemoglobin and haematocrit (p less than 0.01) with no difference between the postoperative and discharge values. Adequate blood replacement was determined by the equation: (Formula: see text) Extensive invasive monitoring is not routinely required for adequate blood replacement or the detection of leaks between the systemic and isolated circulation.

Adult↗

Generalized dominant epidermolysis bullosa simplex: decreased activity of a gelatinolytic protease in cultured fibroblasts as a phenotypic marker.

To characterize biochemical traits associated with various forms of epidermolysis bullosa (EB), we used skin fibroblast cultures to measure a gelatin-specific neutral metalloprotease. Compared to normal cultures, levels of this gelatinase were 7-fold decreased in cell cultures from 3 patients from 3 kindreds with generalized dominant EB simplex of the Koebner type (DEBS-K) (p less than 0.001). The specificity of this trait was shown in several ways. The growth kinetics and total protein synthesis of the cells were unaltered. The activity of lactic dehydrogenase, a cytoplasmic enzyme, was also unaltered, indicating the integrity of the cells was not compromised. The decrease in gelatinase activity is specific for generalized DEBS-K, since cultures from recessive dystrophic EB, recessive junctional EB, dominant dystrophic EB, and a second genetic type of DEBS all fail to show this defect. However, since it has been suggested that DEBS-K and the localized form of DEBS, the Weber-Cockayne type (DEBS-WC), may represent allelic mutations of varying severity, we measured gelatinase activity in cell cultures of 13 patients of this type. The levels displayed a biphasic segregation in which 7 of 13 values were equal to, or greater than, the mean activity of control cells. Cultures from the remaining 6 patients were greater than 1 SD below the mean control value and approximated those seen in the generalized DEBS-K patients. These studies suggest that the decrease in gelatinolytic activity is a marker for DEBS-K and that DEBS-K and DEBS-WC may be closely related genetic disorders in which the defect in gelatinolytic protease represents a pleiotropic effect of the gene for DEBS or is genetically linked to the DEBS gene.

Adolescent↗

Retinoic acid inhibition of collagenase and gelatinase expression in human skin fibroblast cultures. Evidence for a dual mechanism.

Human skin fibroblast cultures have been employed to study the effects of a variety of vitamin A analogues (retinoids) on the expression of two enzymes involved in collagen degradation in the skin, collagenase and a gelatinolytic protease. In normal and recessive dystrophic epidermolysis bullosa fibroblast cultures, retinoic acid compounds were effective inhibitors of the accumulation of both enzymes in the culture medium with half-maximal inhibitions occurring at 0.25-1 microM for collagenase and at 3-6 microM for the gelatinolytic protease. Various retinoids exhibited differing degrees of inhibitory actions, so that at a 1 microM concentration, relative inhibitions were: 13-cis-retinoic acid greater than all-trans-retinoic acid greater than aromatic retinoid (Ro 10-9359) much greater than retinol. The retinoic acid-mediated decrease in collagenase activity was accompanied by a parallel decrease in immunoreactive collagenase protein, suggesting that the retinoic acids were acting to inhibit synthesis of the enzyme. However, an additional effect of these agents was encountered. Although the retinoids themselves had no direct collagenase inhibitory action, medium derived from cultures maintained in these retinoids showed direct inhibitory capacity which was dependent both on the concentration of retinoic acid and on the length of time in culture. The results suggest that the retinoic acids modulate collagenase in vitro by two mechanisms: by decreasing the synthesis of enzyme protein and by modulating the expression of an inhibitory molecule.

Cells, Cultured↗

Regulation of gelatinase in human skin organ cultures by glucocorticoids.

Hydrocortisone and dexamethasone prevent the appearance of gelatinase in serum-free explant cultures of normal human skin. Hydrocortisone inhibits maximally at 10(-6) M and dexamethasone at 10(-8) M in culture medium. Glucocorticoids at these concentrations do not cause a generalized decrease in protein synthesis; thus the effect on gelatinase shows specificity. The reduction in gelatinase activity caused by dexamethasone can be overcome in the presence of dexamethasone 21-mesylate, a glucocorticoid antagonist that binds irreversibly to the cytoplasmic steroid receptor. These data suggest that the enzymes of collagen degradation, collagenase and gelatinase, may be coregulated.

Depression, Chemical↗

Inhibition of collagen degradative enzymes by retinoic acid in vitro.

The effects of a variety of retinoids on collagenase and gelatinase expression have been examined in skin fibroblast cultures derived from normal volunteers and from patients with the hereditary blistering disorder, recessive dystrophic epidermolysis bullosa. Both 13-cis- and all-trans-retinoic acid were effective inhibitors of collagenase production in both cell types. In the case of collagenase, the inhibition of collagenase activity was paralleled by a reduction in immunoreactive enzyme protein, suggesting that these retinoids act by inhibiting synthesis and/or secretion of the enzyme. Retinoic acid also inhibited production of the second enzyme in the collagen degradative pathway, gelatinase. In this case, the decrease in gelatinase activity was equal to or slightly greater than the achieved in collagenase expression. The observation that certain retinoids modulate the two crucial enzymes in the degradation of collagen in the skin suggests that they might be useful therapeutic agents in recessive dystrophic epidermolysis bullosa, a disease in which the pathogenesis of blistering is in part related to connective tissue destruction.

Cells, Cultured↗

Arterial and venous dilation by nitroprusside and nitroglycerin--is there a difference?

Whole-body arterial and venous dilating properties of nitroprusside and nitroglycerin were compared with each other in 20 adult patients during cardiopulmonary bypass for coronary artery bypass or valvular heart surgery and were compared with simultaneous forearm vascular measurements. Nitroprusside was found to be a more effective whole-body arterial vasodilator and nitroglycerin a better whole-body venous vasodilator when each drug was infused at rates of 1.5 and 2.0 microgram/kg/min. No difference in whole-body vasodilation between the two drugs was found at 1.0 microgram/kg/min. Forearm plethysmography did not distinguish between the two drugs at any dose level.

Adult↗

Changing specialties: do anesthesiologists differ from other physicians?

Career choices of physicians frequently change after senior year in medical school. Although previous studies have documented the magnitude of these changes, they contain no information concerning anesthesiologists. Changes in specialties of 1151 physicians, graduates from the same medical school, between the years 1968 and 1976 were studied. Of these physicians, 35 (3%) are presently engaged in the practice of anesthesiology. Of 31 physicians who planned careers in anesthesiology as seniors, 26 (84%) remained in anesthesiology. Nine physicians changed from other specialties to anesthesiology. The ability of anesthesiology to retain physicians who originally planned to specialize in it, or to gain physicians from other fields, was not different from that found in other specialties studied.

Anesthesiology↗

Purification and properties of a gelatin-specific neutral protease from human skin.

A neutral protease with a marked specificity for gelatin as a protein substrate has been purified to homogeneity from medium of human skin in serum-free explant culture. The pH optimum of this gelatinase is between 7.0 and 7.5 with little or no activity displayed below pH 5. Inhibition by EDTA, ethylene glycol bis(beta-amino-ethyl ether)N,N,N',N'-tetraacetic acid (EGTA), and 1,10-phenanthroline suggest that the enzyme is a metalloendopeptidase. Calcium concentration-dependent inhibition of the enzyme by EGTA and EDTA suggest further that there is a requirement for extrinsic calcium. Indeed, removal of calcium and reduces enzyme activity, and subsequent addition of calcium restores full activity. The gelatinase is not inhibited by serine protease inhibitors but is inhibited by cysteine, dithiothreitol, and beta-mercaptoethanol. It is also inhibited by a macromolecular inhibitor of collagenase which has been purified from human skin fibroblasts. The apparent molecular weight of this enzyme, as determined by gel filtration is 120,000-150,000. The enzyme is a glycoprotein, as indicated by staining with periodic acid-Schiff reagent and by its affinity for lectins. Human skin gelatinase shows little or no reactivity toward common protein substrates, such as hemoglobin or casein, and does not cleave helical collagen. Two sites of cleavage in the sequence of gelatin, Gly-Ile and Gly-Leu, have been positively identified using synthetic substrates and tryptic peptides of collagen.

Amino Acid Sequence↗

Autonomic hyperreflexia during upper extremity surgery.

A case is presented of autonomic hyperreflexia in a quadriplegic patient occurring during upper extremity surgery. Tourniquet ischaemia is proposed as the likely causative stimulus. An understanding of the afferent neural pathways involved in this physiological response may be useful in better understanding the subjective phenomena of tourniquet pain in neurologically intact individuals.

Adult↗

Comparison of the cardiovascular effects of bolus v. incremental administration of thiopentone.

Twenty unpremedicated patients (ASA grade I) were assigned randomly to receive thiopentone in 50-mg increments every 15 s until loss of lash reflex (group I) or as a 4-mg kg-1 bolus (group II). Arterial pressure, heart rate, systolic time intervals and end-tidal carbon dioxide were measured in the control state and then every 30 s. The mean dose of thiopentone in group I was 5.58 +/- 1.24 (SD) mg kg-1 which was significantly larger than in group II (P less than 0.001). Both groups exhibited similar decreases in arterial pressure and increases in heart rates. The degree of cardiac depression revealed from measurement of the systolic time intervals, indexed for heart rate, was equal in the two groups.

Anesthesia, Intravenous↗

Unilateral pulmonary oedema: a case report.

We have presented a case of unilateral pulmonary oedema which we feel is secondary to obstruction of the right main bronchus during spontaneous respiration. An anode tracheal tube was introduced through a tracheostomy during operation in a man with pre-existing pulmonary and cardiac disease. At the end of the anaesthetic, acute obstruction to ventilation of the right main bronchus developed with the tube still in place and the patient breathing spontaneously. The obstruction was relieved, by repositioning of the tracheal tube, but not before the patient developed right unilateral pulmonary oedema.

Aged↗