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Biomedical subjects

A Gotlieb

Publications and source records attributed to A Gotlieb.

At least 19 recordsLinked to original sources

Impaired vascular reactivity following angioplasty is mainly due to endothelial injury.

Vasoconstriction occurs frequently following coronary angioplasty and is implicated in the pathogenesis of abrupt closure and restenosis. Control of vasomotor tone is regulated in part directly by smooth muscle cells and indirectly through the endothelium. To study the mechanisms underlying vasoconstriction, the effect of angioplasty and endothelial denudation on endothelium-dependent and -independent relaxation was examined in 15 mongrel dogs. Percutaneous transluminal angioplasty and endothelial denudation of the right femoral artery were performed. Endothelial injury was assessed by adhesion of indium-111-labeled platelets. Endothelium-dependent and -independent relaxation were assessed using acetylcholine and nitroglycerin, respectively. Vessels precontracted with potassium chloride and exposed to acetylcholine showed impaired relaxation in both the angioplasty and denuded groups (angioplasty = 14 +/- 5%, denuded = 0 +/- 0%, normal = 73 +/- 12%; P less than 0.05 for both angioplasty and denuded compared to normal). Precontraction with phenylephrine yielded similar results (angioplasty = 16 +/- 8%, denuded = 4 +/- 2%, normal = 39 +/- 10%; P less than 0.05 only for denuded segment compared to normal). Segments precontracted with phenylephrine and exposed to nitroglycerin did not demonstrate impaired relaxation (angioplasty = 73 +/- 9%, denuded = 68 +/- 9%, normal = 71 +/- 7%, P = ns). Mean indium-111 counts were similar in both the angioplasty and denuded segments (2820 +/- 1481 and 2963 +/- 1228 counts/min/g, respectively) compared to a lower count in the normal segment (1514 +/- 956 counts/min/g). Thus, angioplasty produces significant vascular injury and impairment of vasodilator function, comparable to that caused by endothelial denudation alone. This implies that vasoconstriction seen following coronary angioplasty may be due to endothelial injury and the resultant loss of control of vasomotor tone.

Acetylcholine

Thrombogenicity of total parenteral nutrition solutions: II. Effect on induction of endothelial cell procoagulant activity.

Thrombosis is a common sequela of total parenteral nutrition. We have recently demonstrated in vitro that hypertonic total parenteral nutrition solutions are potent inducers of a tissue factor monocyte procoagulant activity, the initiating cofactor of the extrinsic clotting cascade. We have further studied, in vitro, the effects of the component solutions of total parenteral nutrition on the induction and modulation of endothelial cell procoagulant activity. Cultured porcine aortic endothelial cells were incubated with (a) 200 microliters of dextrose solution (5%, 10%, 20%, 25%, and 50%), (b) 200 microliters of amino acid solution [full strength (N), one-fourth strength, and one-half strength], and (c) 200 microliters of 10% lipid emulsion. Cocultures of lipid emulsion and 20% dextrose, lipid emulsion and full-strength 10% amino acid solution (N-amino acid), and lipid emulsion and bacterial lipopolysaccharide also were studied. Cells were incubated for intervals of 3-108 h, washed and frozen, harvested, and assayed for endothelial cell procoagulant activity. Units of endothelial cell procoagulant activity were derived from a standard thromboplastin curve. Our results show that amino acid and hypertonic dextrose total parenteral nutrition solutions are able to strongly induce endothelial cell procoagulant activity expression in vitro. In contrast, lipid emulsion significantly inhibited the induction of endothelial cell procoagulant activity by 20% dextrose, N-amino acid, and lipopolysaccharide. These results provide further evidence for the role of the cellular pathways of coagulation in total parenteral nutrition-induced thrombosis. Furthermore, the inhibitory properties of lipid emulsion may be of practical advantage in reducing total parenteral nut induced thrombosis.

Animals

Recovery from heart failure: structural and functional analysis in a canine model.

Chronic, rapid ventricular pacing produces congestive heart failure in the dog. Using echocardiography, the features of developing heart failure were analysed and the capacity of this model for recovery was assessed once pacing had been discontinued. Fifteen dogs were studied; nine were paced at 250 beats/min (bpm) to severe heart failure (5.0 +/- 1.8 weeks) and six served as sham controls. In the paced animals at severe heart failure, two-dimensional echocardiography demonstrated a significant increase in diastolic cross-sectional cardiac area (from 11 +/- 3 to 16 +/- 2 cm2, p less than 0.05), associated with a marked fall n area ejection fraction (54 +/- 8 to 21 +/- 8%, p less than 0.05), and significant left ventricular wall thinning (from 6.0 +/- 0.7 to 4.7 +/- 0.9 mm, p less than 0.05). In addition, significant increases in heart rate (77 +/- 7 to 126 +/- 13 bpm, sinus rhythm; p less than 0.05), respiratory rate (41 +/- 13 to 80 +/- 20 cycles/min, p less than 0.05), and body weight (21 +/- 1 to 24 +/- 3 kg, p less than 0.05) were noted. Serum sodium fell (146 +/- 3 to 140 +/- 8 mmol/L, p less than 0.05), while blood urea nitrogen (6 +/- 2 to 10 +/- 2 mmol/L, p less than 0.05) and creatinine (86 +/- 12 to 101 +/- 15 mmol/d, p less than 0.05) increased. Recovery was characterized by rapid improvement such that all measured parameters normalized by 1 week, except for cross-sectional cardiac area which remained dilated up to 4 weeks (14 +/- 3 cm2, p less than 0.05 versus control).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Torsion of the spleen in a five-and-a-half-month-old infant.

In this report, we describe torsion of the spleen in a five-and-a-half-month-old infant, thus far the youngest reported patient in the literature. Celiac angiography and tuftsin determination confirmed the clinical impression that the pathology was confined to the spleen. The infant underwent a splenectomy and made an uneventful recovery.

Celiac Artery

Benign course of juvenile laryngeal papillomata.

A 17 month-old child with laryngeal papillomata is presented. The symptoms were stridor and gradually developing dyspnea. He underwent two surgical procedures within 4 months, using microsurgical techniques, and eventually recovered. The etiological factors of this rare entity are discussed. The relatively benign course in our patient is stressed, in view of the usual protracted course which is reflected in the literature.

Fibroma

Agenesis of the right diaphragm: repaired with marlex.

A case of a female newborn with agenesis of the right hemidiaphragm is presented. The defect was corrected with a double sheet of Marlex, attached to a rim of endothoracic fascia and muscle. At the age of 5 yr, the child is in perfect health.

Diaphragm

Concentric hemorrhagic necrosis of the myocardium. A morphological and clinical study.

Froty-nine cases of concentric hemorrhagic necrosis of the left ventricular myocardium were reviewed in a series of 97 autopsy studies in patients subjected to cardiopulmonary bypass for various types of cardiac surgery. The gross and microscopic findings were analyzed in order to define the morphologic evolution of the lesion. The extent of involvement was graded by gross examination of serial transverse sections of the heart. Microscopically there were five major histologic changes, probably representing the sequential evolution of the lesion, i.e., contraction bands, subendocardial hemorrhages, coagulative necrosis, healing by granulation tissue, and fibrosis. The location of the lesion conincided with the vulnerable region of the microcirculation. Owing to the implementation of new surgical techniques, the cases were subdivided into two groups, one covering the period from 1963 to 1970 and the other , 1971 to 1974. Concentric hemorrhagic necrosis was less frequent in the more recent group, but when it was present it was more pronounced in the individual heart. The lesion in the earlier group was milder but demonstrated a higher incidence of platelet microthrombi in the heart. In the recent cases concentric hemorrhagic necrosis tended to be more diffuse in aortocoronary bypass than in valvular replacement surgery. We discuss one possible explanation for the development of this lesion, i.e., transient hypoxemia occurring at the time of cardiopulmonary bypass, followed by reperfusion and accelerated necrosis with hemorrhage.

Adult

A general method for the introduction of enzymes, by means of immunoglobulin-coated liposomes, into lysosomes of deficient cells.

Phagocytes of the smooth dogfish (Mustelus canis) contain no endogenous peroxidase within their lysosomes and constitute models for cells genetically deficient in lysosomal enzymes such as myeloperoxidase. We have obtained uptake of over 50% of exogenous horseradish peroxidase, provided the enzyme is exhibited to cells after incorporation into liposomes coated with heat-aggregated (62 degrees, 10 min), isologous IgM. Trapping of horseradish peroxidase (EC 1.11.1.7) by liposomes was established by chromatographic resolution (Sephadex G-200; Sepharose 2B and 4B) of free enzyme from that associated with liposomes; liposome-associated horseradish peroxidase, together with trapped markers of the aqueous compartment (glucose, CrO4 equals), were excluded, and free enzyme and markers were retained. Enzyme and marker trapping was not electrostatic, varied with the molar ratio of charged membrane components, and was reversed by detergent lysis (Triton X-100) of liposomes. Uptake at 30 degrees of aggregated IgM-coated liposomes containing trapped horseradish peroxidase exceeded that of free enzyme of 100-fold, and was more efficient than uptake of horseradish peroxidase presented in uncoated liposomes or in liposomes coated with native IgM. After phagocytosis, peroxidase-rich liposomes were localized exclusively in lysosomes of the phagocytes by ultrastructural histochemistry; the enzyme displayed over 50% latency to osmotic lysis. This method may prove to be of general use in the provision of exogenous enzymes to phagocytic cells genetically deficient in lysosomal hydrolases.

Animals