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Biomedical subjects

P H Plotz

Publications and source records attributed to P H Plotz.

At least 127 records · Page 7Linked to original sources
PubMed1975

Systemic lupus erythematosus. Contrasts and comparisons.

Systemic lupus erythematosus, a disease capable of exhibiting virtually any clinical manifestation, is discussed in detail and the findings are compared to those in other, presumably systemic lupus erythematosus-related connective tissue diseases. More emphasis has been placed on the clinical features than on the numerous laboratory manifestations. The conference begins and ends with a brief consideration of current concepts of pathogenesis and suggests some future investigational directions.

Animals↗
PubMed1975

Unconjugated hyperbilirubinemia. Physiologic evaluation and experimental approaches to therapy.

The plasma concentration of unconjugated bilirubin is determined by the rate at which newly synthesized bilirubin enters the plasma (bilirubin turnover) and the rate of irreversible bilirubin removal by the liver (hepatic bilirubin clearance). Measurement of each of these variables by kinetic studies with radiolabeled bilirubin permits a precise classification of cases of unconjugated hyperbilirubinemia into those due to increased bilirubin turnover (for example, hemolysis), those due to decreased bilirubin clearance (for example, Gilbert's syndrome), and those in which both mechanisms operate. The ability to quantitate hepatic bilirubin clearance makes it possible to detect gilbert's syndrome even in the presence of concomitant hemolysis. Of the hereditary disorders of bilirubin metabolism, Gilbert's syndrome is common but innocuous, whereas Crigler-Najjar syndrome is rare but devastating. An unusual case of Crigler-Najjar syndrome is described in which bilirubin encephalopathy developed at age 10. Various modalities used in an attempt to reduce her plasma bilirubin concentration by either increasing bilirubin clearance or reducing bilirubin turnover are described.

Adult↗
PubMed1975

Cyclophosphamide or azathioprine in lupus glomerulonephritis. A controlled trial: results at 28 months.

Thirty-eight patients with diffuse glomerulonephritis of systemic lupus erythematosus were randomly assigned to add cyclophosphamide, azathioprine, or nothing to low-dose corticosteroid treatment and have been followed for a mean of 21/3 years thereafter. Of the 11 patients with unfavorable outcomes (8 deaths and 2 beginning hemodialyses), 2 occurred on cyclophosphamide, 4 on azathioprine, and 5 on prednisone only. Deaths due to infection occurred on the cytotoxics, while deaths ascribed to central nervous system lupus erythematosus occurred exclusively on prednisone only. Gradual deterioration of renal function was observed in all three groups, most frequently on prednisone only. Undesirable events, some due to drugs, were observed. At the time of reporting, the cytotoxic agents seemed to add marginally to the control of the disease; other treatment schedules should be evaluated.

Adolescent↗
PubMed1974

Removing substances from blood by affinity chromatography. I. Removing bilirubin and other albumin-bound substances from plasma and blood with albumin-conjugated agarose beads.

Substances such as bilirubin that bind tightly to plasma proteins cannot readily be removed from blood. We describe here the use of affinity chromatography as a new approach to the removal of proteinbound metabolites and toxins from blood. Agarose beads were coupled via cyanogen bromide to human serum albumin so as to contain 30-50 mg of albumin/g wet wt. Such beads, when exposed to plasma from a patient with congenital nonhemolytic jaundice labeled with [(14)C]-bilirubin, bound more than 150 mug bilirubin/g of beads. The binding was saturable, concentration-dependent, relatively independent of flow rate, and reversible by elution with plasma, albumin, or 50% (vol/vol) ethanol. The beads could be repeatedly reused without loss of efficiency after ethanol elution and long storage in the cold. Salicylate, cortisol, and taurocholate, which bind weakly to albumin, were retarded by the beads but eluted with neutral buffer. Thyroxine, taurolithocholate, chenodeoxycholate, and digitoxin bound tightly but were eluted with 50% ethanol. Digoxin did not bind at all. When whole blood was passed over agarose-albumin beads, bilirubin was removed, calcium and magnesium fell slightly, but red cells, white cells, platelets, clotting factors, and a variety of electrolytes and proteins were substantially unchanged. Agarose-albumin beads may be useful for removing protein-bound substances from the blood of patients with liver failure, intoxication with protein-bound drugs, or specific metabolic deficits. Furthermore, it may be possible to make useful adsorbents by attaching other proteins to agarose or other polymer beads.

Bilirubin↗
PubMed1974

Removing substances from blood by affinity chromatography. II. Removing bilirubin from the blood of jaundiced rats by hemoperfusion over albumin-conjugated agarose beads.

In vitro studies indicate that bilirubin and other albumin-bound substances can be efficiently removed from plasma by filtration over albumin-conjugated agarose beads. The effectiveness of this technique in vivo was investigated in rats by using a closed extracorporeal hemoperfusion system. Five Gunn rats whose endogenous bilirubin pool had been labeled with [(3)H]bilirubin and five Sprague Dawley rats with surgically created biliary obstruction were chosen as models of unconjugated and conjugated hyperbilirubinemia. Indocyanine green was injected into rats and its removal also studied. In the Gunn rats, 98% of the bilirubin was removed from plasma during the initial pass over the column as determined isotopically and chemically. Plasma bilirubin levels fell more than 70% from 8.2+/-1.6 mg/100 ml (mean+/-SD) to 2.6+/-0.5 mg/100 ml during a 1-h hemoperfusion. An average of 1,061 mug of bilirubin was recovered from the columns, representing 22.5+/-4.2% of the total exchangeable bilirubin pool and 96+/-36.4% of the plasma pool. Results were similar in the rats with biliary obstruction and in those given indocyanine green. Normal Sprague Dawley rats experience minimal changes in formed blood elements, electrolytes, and proteins as the result of hemoperfusion. When the total volume of the column did not exceed 51% of the estimated blood volume of the animal, the survival rate was 100% in 20 studies, and the procedure was without observable ill effect. Extrapolation of both in vitro and in vivo data to man suggests that extracorporeal hemoperfusion over albumin-agarose columns may be a practical means of assisting hepatic excretory function.

Animals↗
PubMedDate not supplied

Effect of aspirin on liver tests in patients with RA or SLE and in normal volunteers.

Aspirin was given to 20 patients with RA, 16 patients with SLE, and 3 normal volunteers. Four of the RA patients, 7 of the SLE patients, and 1 normal volunteer developed abnormal liver tests, during the study. The abnormalities (elevated transaminases) were most frequent and of rapid onset in patients with cliniclaly active SLE. Increases in BUN and creatinine related to aspirin were observed in several subjects. In a retrospective survey of 80 patients with SLE, aspirin appeared responsible for two-thirds of episodes of liver test abnormalities in 19 patients.

Aspirin↗
PubMedDate not supplied

Enzyme replacement therapy in the mouse model of Pompe disease.

Deficiency of acid alpha-glucosidase (GAA) results in widespread cellular deposition of lysosomal glycogen manifesting as myopathy and cardiomyopathy. When GAA-/- mice were treated with rhGAA (20 mg/kg/week for up to 5 months), skeletal muscle cells took up little enzyme compared to liver and heart. Glycogen reduction was less than 50%, and some fibers showed little or no glycogen clearance. A dose of 100 mg/kg/week resulted in approximately 75% glycogen clearance in skeletal muscle. The enzyme reduced cardiac glycogen to undetectable levels at either dose. Skeletal muscle fibers with residual glycogen showed immunoreactivity for LAMP-1/LAMP-2, indicating that undigested glycogen remained in proliferating lysosomes. Glycogen clearance was more pronounced in type 1 fibers, and histochemical analysis suggested an increased mannose-6-phosphate receptor immunoreactivity in these fibers. Differential transport of enzyme into lysosomes may explain the strikingly uneven pattern of glycogen removal. Autophagic vacuoles, a feature of both the mouse model and the human disease, persisted despite glycogen clearance. In some groups a modest glycogen reduction was accompanied by improved muscle strength. These studies suggest that enzyme replacement therapy, although at much higher doses than in other lysosomal diseases, has the potential to reverse cardiac pathology and to reduce the glycogen level in skeletal muscle.

Animals↗