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Biomedical subjects

R J Elin

Publications and source records attributed to R J Elin.

At least 73 records · Page 4Linked to original sources

Blood magnesium parameters do not differ with age.

The relationship between age and blood magnesium (Mg) parameters has not been defined. Mg measurements in plasma, red blood cells (RBCs), and mononuclear blood cells (MBCs) were made in 104 normal volunteers (43 males and 61 females, ages 11-75 years). MBCs were separated from blood using a discontinuous Ficoll-Hypaque gradient. The mean values (+/- SEM) were as follows: plasma Mg 1.63 +/- 0.01 mEq/L, RBC Mg 4.55 +/- 0.06 mEq/L, MBC Mg content 72.8 +/- 1.0 fg/cell, and MBC Mg concentration 19.6 +/- 0.3 mEq/L. We compared these parameters with age (intervals of 10 years) using analysis of variance (ANOVA) and found no significant differences (p greater than 0.05). Thus, plasma, RBC, and MBC Mg parameters do not vary significantly between the ages of 11 and 75 years.

Adolescent↗

Antibiotics versus cardiovascular support in a canine model of human septic shock.

This study compares the efficacy of antibiotics (cefoxitin and gentamicin), cardiovascular support (fluids and dopamine titrated by intravascular monitoring to hemodynamic end points), and a combination of these two therapies in dogs with septic shock induced by an intraperitoneal clot containing Escherichia coli. Survival rates were 0, 13, 13, and 43% in groups receiving no therapy (controls), antibiotics alone, cardiovascular support alone, or combined therapy (P less than 0.01), respectively. The improved survival observed in the group receiving combined therapy considerably exceeded that in the groups receiving either therapy alone (i.e., a synergistic increase P less than 0.05). Compared with antibiotics alone, cardiovascular support alone prolonged survival time (P less than 0.006). All groups developed similar and significant (P less than 0.01) increases in endotoxin levels; however, in the combined therapy group, nonsurvivors (compared with survivors) had higher levels of endotoxemia (P less than 0.05). Although survivors and nonsurvivors in the combined therapy group required similar (P = 0.10) quantities of fluid therapy, nonsurvivors gained more weight (P less than 0.05), suggesting abnormal vascular permeability with extravascular retention of fluids in the nonsurvivors. This study demonstrates that antibiotics alone and cardiovascular support alone are relatively ineffective in the treatment of septic shock. When combined, however, these two therapies provide moderately successful treatment for this highly lethal disorder.

Animals↗

Pseudomonas aeruginosa compared with Escherichia coli produces less endotoxemia but more cardiovascular dysfunction and mortality in a canine model of septic shock.

We investigated the effects of two different Gram-negative bacteria and radiation-induced leukopenia on endotoxemia, cardiovascular abnormalities, and mortality in a canine model of septic shock. Serial hemodynamics were measured in conscious dogs using radionuclide heart scans and thermodilution cardiac output catheters. Plasma endotoxin concentrations were determined with a chromogenic Limulus amebocyte lysate assay. Viable Pseudomonas aeruginosa or Escherichia coli implanted intraperitoneally produced concordant hemodynamic patterns of septic shock (p less than 0.01). Endotoxin concentrations were more than tenfold lower in dogs infected with P aeruginosa compared with E coli (p less than 0.0001). Despite lower endotoxin levels, P aeruginosa-infected dogs had a higher mortality (p less than 0.01), more severe hypotension (p less than 0.05), and greater depression of the left ventricular ejection fraction (p less than 0.05) than dogs with E coli sepsis. A nonlethal E coli challenge combined with leukopenia (induced by a nonlethal dose of radiation) resulted in a mortality of 60 percent (p less than 0.01) without greater cardiovascular dysfunction or higher endotoxin concentrations. These findings suggest that bacterial products other than endotoxin and host-related factors may be important contributors to the toxicity, cardiovascular instability, and mortality of Gram-negative septic shock. Quantitative determinations of plasma endotoxin are unlikely to correlate with the clinical severity of septicemia in heterogeneous patient populations infected with different Gram-negative organisms.

Animals↗

Effect of intravenous magnesium sulfate on blood magnesium parameters.

Magnesium sulfate was administered intravenously (0.6 mEq/kg body weight over 10 min) to 13 patients with hypertrophic cardiomyopathy undergoing electrophysiologic testing. Total serum, ultrafilterable and protein-bound serum, mononuclear blood cell (MBC) content and concentration, and red blood cell (RBC) concentration of Mg were measured at the following intervals: (1) baseline (before Mg infusion), (2) at the end of infusion, and (3) approximately 40 min after the end of infusion. The total serum, ultrafilterable, and protein-bound fractions rose immediately after infusion and fell by 40 min. The RBC Mg rose and fell less sharply than the serum parameters after Mg infusion. In contrast, the MBC Mg content continued to rise significantly at 40 min after Mg infusion, and MBC concentration showed a continued trend to rise, although this was not statistically significant.

Adult↗

Blood magnesium status of patients with parathyroid disease.

The blood magnesium status--plasma and red blood cell (RBC) concentration and mononuclear blood cell (MBC) content of magnesium and parathyroid hormone (PTH) were determined in 6 patients with chronic hypoparathyroidism and 9 patients with primary hyperparathyroidism before and after surgical cure of the disease. The magnesium content of MBCs and concentration of RBCs increased significantly (p less than 0.01) after the surgical correction of primary hyperparathyroidism. Patients with chronic hypoparathyroidism had significant increase (p less than 0.05) of magnesium in RBCs and MBCs compared with the control group. No significant difference was observed for the plasma magnesium concentration for hypoparathyroid patients compared with the control group and hyperparathyroid patients before and after surgical care. These results suggest that endogenous PTH affects the concentration of magnesium in RBCs and magnesium content in MBCs but does not alter significantly the concentration of magnesium in plasma.

Erythrocytes↗

Changes in laboratory results for cancer patients treated with interleukin-2.

The systemic administration of interleukin-2 (IL-2) can lead to significant antitumor responses in some patients with metastatic cancer in whom standard therapy has failed. A limitation of this immunotherapy is the toxicity associated with IL-2 infusion. To assess toxicity, we determined aspartate aminotransferase (AST; EC 2.6.1.1), alanine aminotransferase (ALT; EC 2.6.1.2), gamma-glutamyltransferase (GGT; EC 2.3.2.2), lactate dehydrogenase (LD; EC 1.1.1.27), alkaline phosphatase (ALP; EC 3.1.3.1), creatine kinase (CK; EC 2.7.3.2), total bilirubin (TBI), direct bilirubin (DBI), creatinine, urea nitrogen, and C-reactive protein in serum from 21 patients before and during five consecutive days of IL-2 treatment. Ten patients were followed for an additional five days after the end of IL-2 therapy. The IL-2 infusion caused liver toxicity and prerenal azotemia, as evidenced by significant increases (P less than 0.05) of all analytes except CK by day 1. There was a progressive increase in the results (except CK) for these tests until IL-2 treatment was stopped. Seven tests related to liver function (AST, ALT, GGT, LD, ALP, DBI, and TBI) showed increases, but the test results indicated significant improvement and moved toward the baseline value five days after the end of IL-2 therapy. Concentrations of creatinine and urea nitrogen in serum were normal three days after the cessation of IL-2 therapy.

C-Reactive Protein↗

Intravenous fluorescein interference with clinical laboratory tests.

The results of laboratory tests performed after fluorescein angiography may be erroneous because of interference by intravenous fluorescein. We investigated this potential interference in four adults at intervals of five minutes, three hours, six hours, and 12 hours after fluorescein injection. We used a panel of serum and urine chemistry tests on seven commonly used instruments. A significant change in the reported concentration of a serum or urine analyte was defined as a result beyond +/- 3 coefficients of variation of the preinjection baseline value for the test on a specific instrument. The determinations of creatinine, total protein, cortisol, digoxin, quinidine, and thyroxine in serum were affected by intravenous fluorescein. The urine tests were unaltered. The physician must be aware of the problem of interpreting clinical chemistry results after fluorescein angiography.

Adult↗

Dysphagia in bulimia nervosa.

The findings on 13 patients with bulimia nervosa referred for evaluation of salivary glands and swallowing patterns are presented. Each patient completed a medical, oral, and social history questionnaire. A complete oral examination supported by appropriate dental radiographs and photographs was conducted. Unstimulated and stimulated parotid and submandibular saliva was collected. The presence or absence of pharyngeal and velar gag reflexes was ascertained. Real-time ultrasound scanning and barium swallow studies were used to evaluate the oral-motor functions while swallowing on 6 of the subjects. Activity of the pharynx, larynx, and esophagus was recorded during the videofluorographic studies. Saliva concentrations of amylase were determined in the referred subjects as well as 13 age-matched healthy controls. No significant difference was detected between the salivary gland flow rates and amylase concentrations of the two groups, whether stimulated or unstimulated. The pharyngeal gag reflex was absent in 9 of the 13 bulimic patients and a velar gag reflex could be elicited in only 1. All of the normal controls had both gag reflexes. All of the patients with bulimia were found to have abnormal oropharyngeal swallow patterns and an increased duration of dry swallow.

Adolescent↗

Role of endotoxemia in cardiovascular dysfunction and mortality. Escherichia coli and Staphylococcus aureus challenges in a canine model of human septic shock.

Using different types of bacteria and a canine model simulating human septic shock, we investigated the role of endotoxin in cardiovascular dysfunction and mortality. Either Escherichia coli (a microorganism with endotoxin) or Staphylococcus aureus (a microorganism without endotoxin) were placed in an intraperitoneal clot in doses of viable or formalin-killed bacteria. Cardiovascular function of conscious animals was studied using simultaneous radionuclide heart scans and thermodilution cardiac outputs. Serial plasma endotoxin levels were measured. S. aureus produced a pattern of reversible cardiovascular dysfunction over 7-10 d that was concordant (P less than 0.01) with that of E. coli. Although this cardiovascular pattern was not altered by formalin killing (S. aureus and E. coli), formalin-killed organisms produced a lower mortality and less myocardial depression (P less than 0.01). S. aureus, compared to E. coli, produced higher postmortem concentrations of microorganisms and higher mortality (P less than 0.025). E. coli produced significant endotoxemia (P less than 0.01), though viable organisms (versus nonviable) resulted in higher endotoxin blood concentrations (P less than 0.05). Significant endotoxemia did not occur with S. aureus. Thus, in the absence of endotoxemia, S. aureus induced the same cardiovascular abnormalities of septic shock as E. coli. These findings indicate that structurally and functionally distinct microorganisms, with or without endotoxin, can activate a common pathway resulting in similar cardiovascular injury and mortality.

Animals↗

von Willebrand factor release induced by endotoxin.

In vitro von Willebrand factor is released from endothelial cells by a variety of stimuli. These studies have provided information on the synthesis, multimeric organization, sites of storage, and release of von Willebrand factor. We have administered endotoxin (Escherichia coli, 4 ng/kg) intravenously to 11 normal volunteers and have followed changes in levels of factor VIII, von Willebrand factor antigen, von Willebrand factor activity (ristocetin cofactor assay), and the multimeric organization of von Willebrand factor. Within 2 hours after injection, the levels of factor VIII, von Willebrand factor antigen, and von Willebrand factor activity rose significantly compared with the preinjection values (p less than 0.001, p less than 0.005, and p less than 0.001, respectively). The levels peaked 4 to 6 hours after the endotoxin injection. The mean peak values of von Willebrand factor antigen and activity were 4.67 microns/ml and 4.62 microns/ml, respectively. The factor VIII level rose to a mean of 2.87 microns/ml. Forty-eight hours after the administration of endotoxin, the von Willebrand factor antigen and activity levels remained significantly elevated (2.62 micrograms/ml and 2.20 microns/ml, respectively), but by 24 hours, the factor VIII level was not significantly elevated (1.47 microns/ml). After endotoxin administration, the agarose gel electrophoresis of von Willebrand factor demonstrated an increase in the largest von Willebrand factor multimers normally present and the appearance of von Willebrand factor multimers larger than those normally present in plasma. The largest von Willebrand factor multimers were present for 2 to 4 hours after the administration of endotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Response of humans to gamma-irradiated reference Escherichia coli endotoxin.

This study assesses the effect of gamma-irradiation of endotoxin given intravenously to healthy human volunteers. The national reference standard endotoxin derived from E. coli was placed in aqueous medium in sterile-sealed ampoules and divided into four groups. One group received endotoxin with no radiation while the other three received endotoxin with gamma-irradiation at doses of 0.18, 0.36, or 1.08 Mrad. These doses of radiation cause characteristic alterations to the endotoxin molecule, primarily to the O-polysaccharide moiety. Each of the four different preparations of endotoxin was given intravenously to four volunteers at a concentration of 4 ng/kg. The responses for clinical symptoms, cortisol, and growth hormone were significantly and progressively reduced by increasing the irradiation to the endotoxin. Most strikingly, no clinical symptoms were noted with the endotoxin exposed to the highest dose of radiation (1.08 Mrad). Fever, vital signs, white blood cell count, and differential exhibited no statistically significant differences among the groups, but the kinetics of change were altered by increasing doses of gamma-irradiation. Irradiated endotoxin was significantly more effective in decreasing the platelet count than untreated endotoxin. The fever index correlated significantly with maximum temperature, change in temperature, white blood cell count index, mature neutrophil count index, and the cortisol index. Thus, there is dissociation of biological activities for endotoxin in humans due to molecular changes primarily in the O-polysaccharide moiety from exposure to gamma-irradiation.

Adult↗

Comparison of magnesium in human lymphocytes and mononuclear blood cells.

The population of mononuclear blood cells (MBCs) separated by a discontinuous gradient from healthy normal volunteers consists of lymphocytes (L), monocytes (M) and relatively few granulocytes (G). We attempted to remove the phagocytic cells (M and G) by pretreatment of the blood with carbonyl iron particles (CIP). In 50 volunteers (21 males and 29 females, ages 17-75, mean 33.3 years), we determined the content and concentration of Mg in MBCs before and after pretreatment with CIP. The results (mean +/- SEM) show a significant decrease in the MBC Mg content (from 3.12 +/- 0.08 to 2.39 +/- 0.05 fmol/cell; p less than 0.0001), concentration (from 10.4 +/- 0.2 to 9.6 +/- 0.3 mmol/l; p less than 0.004) and M percentage (from 14.5 +/- 1.0 to 1.0 +/- 0.2%; p less than 0.0001) after CIP pretreatment. The L percentage significantly increased from 81.6 +/- 1.0 to 96.1 +/- 0.2% (p less than 0.0001) after CIP pretreatment. These date suggest that M have both a larger content and concentration of Mg than L.

Adult↗

Determination of magnesium in granulocytes.

Determination of magnesium in mononuclear blood cells may provide useful information about intracellular magnesium. Mononuclear blood cell preparations are frequently contaminated with granulocytes. We determined the normal reference interval for magnesium content and concentration of granulocytes and compared it with magnesium in mononuclear blood cells. The mean granulocyte magnesium concentration and content were 6.95 (SD 1.25) mmol/L and 3.11 (SD 0.54) fmol per cell, respectively, vs 10.95 (SD 1.70) mmol/L and 3.27 (SD 0.46) fmol per cell in mononuclear cells. The concentration of magnesium in granulocytes was significantly less (P less than 0.001) than in mononuclear blood cells, but the magnesium contents were not significantly different.

Adult↗

Effect of lyophilization on results of five enzymatic methods for cholesterol.

We studied the effect of lyophilization of serum pools on the determination of cholesterol with the enzymatic methods used in five automated analyzers: SMAC (Technicon), the RA-1000 (Technicon), the aca (Du Pont), the TDx (Abbott), and the Ektachem 700P (Kodak). We prepared two serum pools: pool A (2.2 g/L) and pool B (1.9 g/L). We separated each pool into three groups for treatment by lyophilizing or freezing at -20 and -70 degrees C. We determined cholesterol by the above methods at regular intervals during the next 270 days. For all methods, the measured concentration of cholesterol was less for the lyophilized serum than for frozen (P less than 0.007 by the paired-sample t-test). After adjusting for the dilutional effects of reconstitution, the decrease in original value was 0.7% for the SMAC, 1.7% for the RA-1000, 5.7% for the Ektachem, 9.4% for the TDx, and 14.3% for the aca. Lyophilization of cholesterol standards or serum samples may hamper the effective standardization of enzymatic methods and may be a source of apparent inaccuracy (bias) among enzymatic methods.

Autoanalysis↗

Endotoxin-induced platelet activation in human whole blood in vitro.

The effect of purified bacterial endotoxin was studied on human platelets in vitro. In adding up to 1 microgram/mL of a highly purified endotoxin, we found neither aggregation nor ATP release in heparinized or citrated human platelet-rich plasma. On the other hand; endotoxin at concentrations as low as a few ng/mL (as may be found in septic patients) caused platelet aggregation in both heparinized and citrated human whole blood, as monitored by change in impedance, free platelet count, and size. Unlike collagen, the platelet aggregation with endotoxin occurred after a long lag phase, developed slowly, and was rarely coupled with measurable release of ATP. The platelet aggregating effect of endotoxin was dose-dependent and modified by exposure of the endotoxin to ionizing radiation. Thus, the activation of human platelets by "solubilized" endotoxin in plasma requires the presence of other blood cells. We propose that the platelet effect is mediated by monocytes and/or neutrophils stimulated by endotoxin.

Adenosine Triphosphate↗