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B Kirschbaum

Publications and source records attributed to B Kirschbaum.

At least 37 records · Page 2Linked to original sources
PubMed1998

The acidosis of exogenous phosphate intoxication.

BACKGROUND: Severe hyperphosphatemia resulting from the use of laxatives and enemas with high levels of phosphate has been the subject of many case reports. These have generally focused on the hypernatremia and hypocalcemia that develop and become life-threatening. Less attention has been paid to the metabolic acidosis of phosphate intoxication. METHODS: In-depth analysis of a case of severe hyperphosphatemia and review of the literature for cases with sufficient data to permit correlation between the phosphate concentration, acidosis, and anion gap. RESULTS: Marked metabolic acidosis with a large increase in the anion gap was present in our patient. The correlation between these parameters and the plasma phosphate concentration was highly significant. Despite a paucity of data in most case reports, we did uncover other cases of anion gap-positive metabolic acidosis in patients with hyperphosphatemia. CONCLUSIONS: Among high-risk patients, including the elderly and debilitated, the presence of metabolic acidosis, hypernatremia, an increased anion gap, and low plasma calcium levels or a prolonged QT interval on the electrocardiogram should raise suspicion of phosphate intoxication.

Acidosis↗
PubMed1998

The mammalian homologue of Prp16p is overexpressed in a cell line tolerant to Leflunomide, a new immunoregulatory drug effective against rheumatoid arthritis.

Prp2p, Prp16p, Prp22p, and Prp43p are members of the DEAH-box family of ATP-dependent putative RNA helicases required for pre-mRNA splicing in Saccharomyces cerevisiae. Recently, mammalian homologues of Prp43p and Prp22p have been described, supporting the idea that splicing in yeast and man is phylogenetically conserved. In this study, we show that a murine cell line resistant to the novel immunoregulatory drug Leflunomide (Arava) overexpresses a 135-kDa protein that is a putative DEAH-box RNA helicase. We have cloned the human counterpart of this protein and show that it shares pronounced sequence homology with Prp16p. Apart from its N-terminal domain, which is rich in RS, RD, and RE dipeptides, this human homologue of Prp16p (designated hPrp16p) is 41% identical to Prp16p. Significantly, homology is not only observed within the phylogenetically conserved helicase domain, but also in Prp16p-specific sequences. Immunofluorescence microscopy studies demonstrated that hPrp16p co-localizes with snRNPs in subnuclear structures referred to as speckles. Antibodies specific for hPrp16p inhibited pre-mRNA splicing in vitro prior to the second step. Thus, like its yeast counterpart, hPrp16p also appears to be required for the second catalytic step of splicing. Taken together, our data indicate that the human 135-kDa protein identified here is the structural and functional homologue of the yeast putative RNA helicase, Prp16p.

Adenosine Triphosphatases↗
PubMed1998

Hyperglobulinemia with an increased anion gap.

Plasma proteins, especially albumin, account for much of the normal anion gap. The relationship between globulins and the anion gap has not received much attention except for reports of a narrowing of the gap associated with certain monoclonal immunoglobulin G gammopathies. The author presents a patient with polyclonal gammopathy, the magnitude of which correlated strongly and positively with the anion gap, along with data from 400 patients attending a renal hypertension clinic, which show a significant positive correlation between the anion gap and total globulins. These results indicate that both albumin and globulin concentrations should be taken into account when attempting to explain abnormalities or changes in the magnitude of the gap.

Acid-Base Equilibrium↗
PubMed1997

Increased anion gap after liver transplantation.

Massive fibrinolysis after a liver transplant resulted in oliguric renal failure and necessitated the continuous infusion of large quantities of fresh frozen plasma. With the increase in plasma protein concentration, there was a simultaneous increase in the anion gap. These two parameters, the anion gap and total protein or albumin level in the blood, demonstrated a high degree of correlation. Weaker but significant correlations were found in a retrospective analysis of patients with a variety of renal diseases and a population of long-term peritoneal but not hemodialysis patients. This entity of hyperproteinemic acidosis should be added to the list of high anion gap acidoses.

Acid-Base Equilibrium↗
PubMed1996

Functional expression of a fragment of human dihydroorotate dehydrogenase by means of the baculovirus expression vector system, and kinetic investigation of the purified recombinant enzyme.

Human mitochondrial dihydroorotate dehydrogenase (the fourth enzyme of pyrimidine de novo synthesis) has been overproduced by means of a recombinant baculovirus that contained the human cDNA fragment for this protein. After virus infection and protein expression in Trichoplusia ni cells (BTI-Tn-5B1-4), the subcellular distribution of the recombinant dihydroorotate dehydrogenase was determined by two distinct enzyme-activity assays and by Western blot analysis with anti-(dihydroorotate dehydrogenase) Ig. The targeting of the recombinant protein to the mitochondria of the insect cells was verified. The activity of the recombinant enzyme in the mitochondria of infected cells was about 740-fold above the level of dihydroorotate dehydrogenase in human liver mitochondria. In a three-step procedure, dihydroorotate dehydrogenase was purified to a specific activity of greater than 50 U/mg. Size-exclusion chromatography showed a molecular mass of 42 kDa and confirmed the existence of the fully active enzyme as a monomeric species. Fluorimetric cofactor analysis revealed the presence of FMN in recombinant dihydroorotate dehydrogenase. By kinetics analysis, Km values for dihydroorotate and ubiquinone-50 were found to be 4 microM and 9.9 microM, respectively, while Km values for dihydroorotate and decylubiquinone were 9.4 microM and 13.7 microM, respectively. The applied expression system will allow preparation of large quantities of the enzyme for structure and function studies. Purified recombinant human dihytdroorotate dehydrogenase was tested for its sensitivity to a reported inhibitor A77 1726 (2-hydroxyethyliden-cyanoacetic acid 4-trifluoromethyl anilide), which is the active metabolite of the isoxazole derivative leflunomide [5-methyl-N-(4-trifluoromethyl-phenyl)-4-isoxazole carboximide]. An IC50 value of 1 microM was determined for A77 1726. Detailed kinetics experiments revealed uncompetitive inhibition with respect to dihydroorotate (Kiu = 0.94 microM) and non-competitive inhibition with respect to decylubiquinone (Kic = 1.09 microM, Kiu = 1.05 microM). These results suggest that the immunomodulating agent A77 1726 (currently in clinical phase III studies for the treatment of rheumatoid arthritis) is a very good inhibitor of human dihydroorotate dehydrogenase.

Amino Acid Sequence↗
PubMed1995

Study of vascular access blood flow by angiodynography.

Angiodynography has been recommended as a safe and accurate way to determine the blood flow through hemodialysis vascular grafts. This information might be used prophylactically to avert total graft occlusion. We examined the blood flows obtained by this technique after an interval of 6 months in a group of hemodialysis patients whose grafts did not require surgical or radiologic manipulation in the interim. No changes in the mean blood flows were noted during the period of observation. Although a significant correlation was found between the original and follow-up blood flows, the coefficient of determination was only 0.27. The Bland-Altman plot of these data showed that both large decreases and increases in graft flows were recorded for many patients whose graft function did not appear to worsen. Dialysis itself did not seem to alter the measured blood flow. We conclude that caution must be used in interpreting changes in blood flow measured over time by angiodynography. More study of the factors accounting for the variability in blood flow estimations by this technique are needed.

Analysis of Variance↗
PubMed1994

The decline in serum albumin after conversion to high flux, high efficiency dialysis.

Hypoalbuminemia among chronic hemodialysis patients is recognized as a poor prognostic sign. We observed that many of our chronic patients had a progressive decrease in their plasma albumin concentrations after they were converted to high flux, high efficiency dialysis from conventional dialysis mode. This change occurred in the absence of changes in the KT/V and protein catabolic rate (pcr) normalized to body mass. When nitrogen losses were measured, we found no difference in the dialysate concentrations of urea, alpha amino nitrogen, uric acid, or total nitrogen when high flux polysulfone was compared with high efficiency Cuprophan. While urea was the predominant nitrogen solute in all dialysate samples, there were some with a large gap between total and urea nitrogen. Alpha amino nitrogen losses, expressed as leucine equivalents, were substantial, ranging from 8.4 to 9.8 g/3.5 h dialysis treatment. We believe that the increased losses of nitrogen experienced by patients after their conversion to a more efficient method of dialysis and not compensated for by a spontaneous increased intake of protein led to the observed fall in plasma albumin. Both urea and amino acid nitrogen losses need to be accounted for when achievement of higher KT/V dialysis is pursued.

Blood Urea Nitrogen↗
PubMed1994

Recirculation measures with urea and mannitol during hemodialysis.

A simple, accurate, and reproducible method of measuring recirculation in grafts during hemodialysis is essential for improving the efficiency of dialysis. In our studies, plasma samples for plasma urea nitrogen (PUN) were taken from the arterial line of the dialyzer at blood flows (A) of 200, 300, and 400 ml/min, preceded by a 5-min period of equilibration, and at 15 s and 2 min after turning the flow down to 100 ml/min (S), the latter serving as systemic samples. Recirculation was calculated as (S - A)/(S - V). Total blood flow (Qb) through the grafts was measured by color Doppler ultrasound. We found a significant, inverse relationship between recirculation and total flow through the graft at dialyzer Qb of 400 but not 300 or 200 ml/min. The magnitude and prevalence of recirculation was always greater when the 2 min sample was used as S compared to the 15 s sample and as dialyzer Qb increased. As a qualitative, urea-independent measure of recirculation, we assayed the appearance of mannitol in the arterial line in blood drawn 15 s after initiating a mannitol push into the venous line. Blood obtained just prior to the mannitol push was used as the zero blank. Thirteen of 18 patients had a measurable, but low, level of mannitol, 5 did not, and 2 had inconsistent results in studies done on separate days. We conclude that the majority of patients receiving chronic hemodialysis have a low degree of recirculation and that methods relying on urea must be suspected of exaggerating the true degree of recirculation.

Blood Circulation↗
PubMed1992

Lactic acidosis treated with continuous hemodiafiltration and regional citrate anticoagulation.

OBJECTIVE: To evaluate the effectiveness of continuous arteriovenous hemodiafiltration (CAVHD) using citrate as the anticoagulant for the treatment of lactic acidosis in patients with renal failure. DESIGN: Case series with careful monitoring of the clinical course of patients being treated in a medical or surgical ICU. SETTING: University hospital ICU. PATIENTS: Two patients with lactic acidosis are described, along with our experience using CAVHD and citrate in other clinical settings. INTERVENTIONS: CAVHD was used to manage renal failure, while a continuous infusion of citrate was administered to maintain patency of the extracorporeal circuit. MEASUREMENTS: Total and ionized serum calcium concentrations and citrate concentrations were monitored. MAIN RESULTS: CAVHD with citrate as the anticoagulant proved to be a convenient means of managing vascular volume, serum electrolyte concentrations, acid-base balance, and replacement renal function requirements in the setting of severe lactic acidosis, oliguric renal failure, and hemorrhagic diathesis. CONCLUSIONS: CAVHD with citrate as the anticoagulant can be recommended as effective therapy for selected patients, but careful monitoring is needed to avoid serious complications.

Acidosis, Lactic↗
PubMed1991

Platelet activating factor acetylhydrolase activity in the urine of patients with renal disease.

Platelet activating factor has been demonstrated in blood and urine and has a broad range of effects on kidney function. The kidney possesses the enzymes responsible for PAF synthesis as well as the specific acetylhydrolase which deactivates PAF. We used a radioactive assay to measure PAF-acetylhydrolase activity in urine samples obtained from normal individuals and patients with various nephropathies. Activity was detected in the majority of normal urines with a mean + 2 SD = 0.70 nmol/30 min/ml. Activity exceeding this value was measured in the urines of 11 of 14 patients with diabetes mellitus, 14 of 22 with glomerulonephritis, and 5 of 16 with hypertensive renal disease. Further study is necessary to relate urine hydrolase activity to specific functional and structural abnormalities of the kidney.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1991

Acid-base regulation in hemodialyzed renal failure patients: effect of serum proteins and bicarbonate buffering.

Interpretation of acid-base balance in human physiology relies on the accuracy of the Henderson-Hasselbalch equation governing pH, HCO3- concentration, and dissolved CO2 in blood. The influence of strong ions and plasma proteins is not generally assigned any quantitative importance. We have taken advantage of the electrolyte and acid-base abnormalities of patients with end stage renal failure to explore the interrelationship among these factors as they pertain to pH maintenance. We find a complex association between pH and plasma protein fractions. pH failed to correlate with the strong ion difference, net cationic equivalency of plasma proteins, pCO2, or serum phosphate considered singly or together. The pK1' for the dialysis population differed significantly from 6.10. The largest calculated value was 6.285. This difference was independent of the dialysate buffer anion composition. The loss of CO2 from blood during sample preparation in the clinical laboratory may fully account for the increase in calculated pK1' and may explain why measured venous rather than arterial total CO2 more closely matches the arterial blood gas calculated HCO3-.

Acid-Base Equilibrium↗
PubMed1991

A case of propylene glycol toxic reaction associated with etomidate infusion.

For the treatment of postoperative seizures and prevention of brain edema, an etomidate drip was used in conjunction with phenytoin, diazepam, pentobarbital, and phenobarbital in a 70-year-old woman. During a period of 24 hours, the patient received in excess of 479 g of propylene glycol, which was present at 35% (vol/vol) concentration in the undiluted etomidate. The propylene glycol toxic reaction resolved after the infusion was stopped.

Acidosis, Lactic↗
PubMed1989

The pK'1 of the carbonic acid-bicarbonate buffer system in hemodialyzed patients.

Blood gas analysis is crucial for the proper evaluation of systemic acid-base disorders, but several reports have been critical of the current approach which relies on the Henderson-Hasselbalch equation and other possibly erroneous assumptions about the bicarbonate-carbonic acid buffer system of blood. This report studied renal failure patients receiving dialysis and nondialyzed medical patients with respect to variations of the pK'1 of carbonic acid dissociation and discrepancies between measured and calculated bicarbonate. Among dialyzed patients, the mean pK'1 differed significantly from 6.10, and a significant difference was found between calculated and measured total CO2 even though all assays were performed on the same arterial blood. Significant correlations were observed between pK'1 and calculated-measured total CO2 as well as serum phosphate converted to mEq/l in the dialyzed group. These data suggest that there is a need to reevaluate current acid-base analysis, especially as it is applied to very seriously ill individuals.

Acid-Base Imbalance↗
PubMed1989

Comparison of indirect methods to estimate plasma volume changes during hemodialysis.

Changes in plasma volume and intravascular protein mass were studied in a group of patients receiving routine hemodialysis. The methodology involved measuring pre- and post-dialysis hematocrits, total plasma proteins, colloid osmotic pressure, albumin and IgG concentrations. Correlations were sought among the plasma volume changes provided by equations using the listed, measured variables. The differences between predicted and measured post-dialysis protein concentrations were used to estimate net gain or loss of protein. Overall, no net gain or loss of intravascular proteins was observed, but the results raised the possibility that changes in intravascular proteins might occur in individual cases. These measurements may be useful in evaluating patients with recurrent dialysis-induced hypotension.

Blood Proteins↗