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Biomedical subjects

E J Quebbeman

Publications and source records attributed to E J Quebbeman.

At least 55 records · Page 3Linked to original sources

Continuous 5-fluorouracil infusion and pulse methotrexate/leucovorin for colorectal adenocarcinoma. A report of excessive toxicity.

Thirteen patients with metastatic colorectal adenocarcinoma underwent treatment with continuous ambulatory 5-fluorouracil (5-FU) infusion 300 mg/m2/day and intermittent bolus methotrexate (MTX) (200 mg/m2) with calcium leucovorin (LCV) 10 mg/m2 orally every 6 h X four to eight doses given 24 h after MTX. Although MTX administration was planned every 14 days, the average time between treatments exceeded 19 days (range 14-42) because of excessive toxicity. All patients experienced toxicity at some time in their treatment course, requiring interruption of 5-FU infusion in 12 of 13 patients. Significant toxicities included stomatitis (13 of 13 patients), hand-foot syndrome (8 of 13 patients), and diarrhea (3 of 13 patients). Toxicity did not appear to be minimized by attenuation of MTX and/or 5-FU dosage or by increasing the dose and/or duration of LCV. At this dosage schedule the addition of MTX/LCV to 5-FU infusion results in excessive and unacceptable toxicity and does not appear to improve treatment results.

Adenocarcinoma↗

Tumoricidal effects and patient survival after hyperthermic liver perfusion.

Hyperthermic liver perfusion for four hours at 42.0 degrees C to 42.5 degrees C was used as the sole modality of therapy for cancer confined to the liver in eight patients. Two patients had melanoma, one had cholangiolar carcinoma of the liver, and five had liver metastases from colorectal carcinoma. Two postoperative deaths occurred, both in patients with colorectal carcinoma metastases. Response was indicated by computed tomographic and/or liver biopsy or autopsy findings of tumor necrosis. There were five responders to hyperthermic liver perfusion among the six survivors. Hyperthermic liver perfusion was an effective tumoricidal agent for hepatic metastases from colorectal cancer; ie, tumor necrosis occurred in all five patients, as well as in the two who died, as shown by autopsy findings. Conversion to a disease-free state with hyperthermic perfusion may be possible with other treatment modalities used in combination or sequence.

Body Temperature↗

Alterations in biochemical functions during hyperthermic isolation-perfusion of the human liver.

Hyperthermia (42-42.5 degrees) was applied to the liver of eight patients with cancer in the liver by a technique of isolation-perfusion. Hepatic functional integrity was assessed during perfusion through measurement of multiple perfusate constituents. Data from seven perfusions were available for analysis. During perfusion there was an increase in perfusate lactate, pyruvate, glucose, urea, potassium, alkaline phosphatase, SGOT, and LDH. All increases in these constituents were significant (P less than 0.05) except for potassium. Lactate accumulated throughout the perfusion from an initial level of 3.8 +/- 1.0 mM to 7.6 +/- 3.5 mM at 4 hr. Pyruvate increased over the first 3 hr of perfusion from 0.14 +/- 0.06 mM to 0.80 +/- 0.37 mM before declining to 0.54 +/- 0.24 mM at 4 hr. The L/P (lactate/pyruvate) ratio decreased during perfusion to less than 10 in the first 2 hr, but rose to within normal limits by the end of perfusion. The decreases in L/P ratios were significant (P less than 0.05). Initially there was a rapid rise in perfusate glucose concentrations from 4.5 +/- 0.8 mM to 20.7 +/- 5.4 mM at 2 hr with nonsignificant changes thereafter. Urea levels increased from 0.64 +/- 0.22 mM to 1.92 +/- 0.76 mM. Perfusate potassium increased from the initial level of 7.0 +/- 1.0 mM during perfusion to 8.3 +/- 1.7 mM at 2 hr before declining. SGOT, LDH, and alkaline phosphatase increased during perfusion from 21 +/- 15, 142 +/- 48, and 16 +/- 6 to 176 +/- 22, 472 +/- 53 and 52 +/- 42, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Nitrogen metabolism and lipid peroxidation during hyperthermic perfusion of human livers with cancer.

Isolation-perfusion was used as a means of heating human livers with cancer. Perfusion was at 42-42.5 degrees C for 4 h. Perfusate constituents were analyzed in an attempt to identify factors contributing to the hepatotoxic effects of hyperthermia. During perfusion the perfusate constituents analyzed were: urea; total amino acids; uric acid; malonaldehyde; and lysosomal enzymes. Hepatic ammonia for urea synthesis is derived from degradation of amino acids, amines, and nucleic acids. An increase in proteolysis was reflected in the increase in urea from 0.6 +/- 0.2 mM to 1.9 +/- 8 mM and total amino acids from 1.0 +/- 0.6 mM to 4.4 +/- 1.7 mM during the 4 h of perfusion at 42-42.5 degrees C. An increase in purine catabolism occurred as evidenced by an increase in perfusate uric acid from 1.7 +/- 1.0 mg/100 ml to 6.1 +/- 2.7 mg/100 ml. Free oxygen radicals, which can lead to lipid peroxidation, are generated by the action of xanthine oxidase on xanthine. Lipid peroxidation occurring during perfusion was assessed by an increase in malonaldehyde from 2.3 +/- 1.3 microM to 10.4 +/- 10.0 microM. An increase in acid phosphatase in the perfusate from 38 +/- 15 units/liter to 78 +/- 45 units/liter occurred, suggesting labilization of lysosomes, perhaps through lipid peroxidation. Proteolysis and lipid peroxidation are suggested to be two interrelated factors contributing to heat toxicity in the perfused human liver with cancer.

Amino Acids↗

A quality control analysis of aminoglycoside management.

Aminoglycoside administration practices were evaluated in a teaching hospital using three study methods: a chart review of 40 randomly selected patients receiving aminoglycosides was conducted retrospectively; 93 health care personnel involved in ordering and administering aminoglycosides to patients were interviewed regarding their understanding of aminoglycoside utilization practices; and ten patients having serum peak and trough aminoglycoside determinations were closely monitored for accuracy of dose administration and obtaining blood specimens at appropriate times. The chart review showed that during 15 of 32 evaluable therapy courses no determinations of serum aminoglycoside concentration were obtained. The survey demonstrated that only 24% of the residents actually used the results of peak and trough determinations to adjust dosage regimens. Direct observation of health care personnel disclosed only two of ten instances in which doses were administered and serum concentration specimens obtained with no apparent problems. Most personnel in our hospital were unaware of these pervasive suboptimal or inconsistent practices associated with aminoglycoside administration and interpretation of laboratory results.

Aminoglycosides↗

Long-term, ambulatory, continuous IV infusion of 5-FU for the treatment of advanced adenocarcinomas.

Twenty-three patients with metastatic adenocarcinomas were treated with long-term, continuous, ambulatory iv infusion of 5-FU. Length of infusion ranged from 54 to 324 days. The usual daily dose was 300 mg/m2. Toxicity was primarily stomatitis. Hand/foot syndrome occurred in 11 patients. Nausea, vomiting, myelosuppression, and alopecia were not observed. Thirteen patients had stomatitis. Eighteen patients had evaluable lesions; eight achieved partial response, five had stable disease, and five had progressive disease. Further studies are necessary to confirm the level of tumor response and survival period of patients treated with this method.

Adenocarcinoma↗

Stability of mitomycin admixtures.

The stability of mitomycin in admixtures for continuous intravenous infusion was studied. Mitomycin was reconstituted and diluted to 50 micrograms/mL in polyvinyl chloride minibags containing 5% dextrose injection 50 mL or 0.9% sodium chloride injection 50 mL. Additional mitomycin admixtures were reconstituted with a buffer solution containing monobasic and dibasic sodium phosphate; these were diluted with 5% dextrose injection only. Admixtures were stored at room temperature (27-30 degrees C) and refrigerated temperature (5 degrees C) for 120 days. Mitomycin concentrations in each admixture were tested by high-performance liquid chromatography (HPLC) immediately after admixture and at intervals during storage. Ultraviolet spectra were determined at the same time as HPLC analysis, and the admixtures were visually inspected and tested for pH. Mitomycin concentrations decreased rapidly in the unbuffered admixtures; after 12 hours at room temperature, less than 26% of the drug remained in the dextrose admixture. When the unbuffered admixtures were refrigerated for 12 hours, the mitomycin concentrations decreased 10% in the sodium chloride admixtures and 33% in the dextrose admixtures; after 24 hours, the percentages of drug loss were 23% and 42%, respectively. Mitomycin concentrations in the buffered admixtures showed no substantial decrease during 120 days at 5 degrees C. At room temperature, concentrations decreased 10% after 15 days. When the admixture is buffered to a pH of approximately 7.8, mitomycin is stable in 5% dextrose injection for up to 15 days at room temperature and at least 120 days at 5 degrees C. Unbuffered mitomycin admixtures should not be stored or administered by prolonged i.v. infusion.

Chromatography, High Pressure Liquid↗

A technique for isolated hyperthermic liver perfusion.

Hyperthermia, either alone or combined with chemotherapy, has been shown to be effective in treating cancer. Because some investigators believe that regional hyperthermia may be more effective than whole body hyperthermia, we developed a technique to heat only the liver to 42-43 degrees for 4 hr. The procedure was adapted from a previously described animal model and was performed in four humans. Vascular isolation of the liver was accomplished by cannulating the hepatic artery, the portal vein, and the inferior vena cava followed by occluding the suprahepatic vena cava and the liver was then perfused with blood and nutrients from an oxygenated reservoir. Preliminary results show radiologic and histologic evidence of tumor necrosis or cessation of tumor growth in three of the patients. We believe this technique is safe enough for clinical experimental use and deserves further investigation.

Adult↗

Mechanisms producing hypoxemia during hemodialysis.

Arterial hypoxemia occurs frequently during hemodialysis. Proposed mechanisms for this phenomenon have included hypoventilation and embolism of granulocyte aggregates. We studied 18 patients with endstage renal failure who required chronic hemodialysis, and measured arterial blood gases, pulmonary gas exchange, and dialyzer gas exchange. During use of acetate as a dialysate buffer, PaO2 decreased to 80 +/- 6.8 torr, whereas during use of the bicarbonate buffer oxygen tension remained at 92 +/- 4.9 torr or greater. Hypoventilation and microembolism were not sufficient to explain the degree of hypoxemia during acetate dialysis. Hypoxemia occurred only after the 1st exposure to acetate; neither an instantaneous change to bicarbonate nor stopping dialysis restored oxygen tension to normal. We conclude that a pharmacologic action of acetate adversely affects lung function, aggravating the decreased alveolar oxygen tension (PAO2) due to hypoventilation. Hypoxemia was not present when bicarbonate was used. Acetate buffer should not be used for dialysis in patients with unstable cardiovascular or respiratory systems.

Acetates↗

Autotransfusion in complex abdominal aneurysms.

We have used a simple adaptation of the cardiotomy suction apparatus for autotransfusion during operation for four aortocaval fistulas and two ruptured internal iliac aneurysms. This has allowed significant blood salvage and maintenance of intraoperative hemodynamic stability. We have had no intraoperative complications and have noted no renal or pulmonary compromise postoperatively. One patient had minor coagulopathy postoperatively that was corrected with fresh frozen plasma and platelet transfusion during the first 12 hours. Autotransfusion for aortocaval fistulas and ruptured internal iliac aneurysms is safe, simple, clinically beneficial and cost effective.

Aneurysm↗

Stability of fluorouracil in plastic containers used for continuous infusion at home.

The stability of fluorouracil when prepared and stored in plastic containers used for continuous infusion in home therapy was studied. Fluorouracil was diluted with 5% dextrose injection. Samples were stored for 16 weeks at 5 degrees C and room temperature in polyvinyl chloride drug reservoirs and at 5 degrees C in elastomeric balloons used in a disposable drug pump. Periodically, samples were tested by a stability-indicating high-performance liquid chromatography (HPLC) assay. At 5 degrees C, there was no significant degradation. At room temperature, there was a progressive increase in fluorouracil concentration, presumably because of evaporation of water. A 10% change in the fluorouracil concentration over 55 days was predicted. Fluorouracil is stable in 5% dextrose injection for at least 16 weeks when stored at 5 degrees C in the two types of containers studied.

Bromouracil↗

Estimating energy requirements in patients receiving parenteral nutrition.

Adequate nutritional support should use a patient's energy expenditure as a guide for administering sufficient but not excessive caloric intake. Sixty-seven patients were evaluated using indirect calorimetry, to determine the applicability of commonly used predictive equations for energy expenditure in patients requiring parenteral nutrition. The frequently used calculation that involves multiplying a constant value of kilocalories per kilogram by the patients weight consistently underestimated the energy requirements of patients of low body weight and overestimated the requirements for heavy body weight. The Harris-Benedict equation was found to be highly dependent on body weight and was not any more accurate than estimations of individual requirements using a simpler weight or surface area regression equation. We recommend that an actual regression equation incorporating body weight or body surface area be used to predict energy requirements and that the oversimplified but common use of the constant value of kilocalories per kilogram be abandoned.

Body Surface Area↗

A re-evaluation of energy expenditure during parenteral nutrition.

Nutritional support regimens are currently based on estimates of energy expenditure, and these estimates are then increased substantially in patients with severe trauma or sepsis because of a presumed hypermetabolic state. Forty-four patients on parenteral nutrition were evaluated using indirect calorimetry to measure actual energy expenditure, and an attempt was made to correlate metabolic rate with clinical diagnosis. We found no statistical difference in metabolic rates between groups of patients classified as malnourished, stressed, or catabolic, If high levels of nonprotein energy substrates are to be administered to a catabolic or "hypermetabolic" patient group, the justification must be on a basis other than a significant increase in actual rate of energy expenditure.

Calorimetry↗

Pulmonary artery pressure monitoring in the surgical intensive care unit. Benefits vs difficulties.

The process of pulmonary artery pressure monitoring in 50 consecutive patients in the surgical intensive care unit was analyzed to determine the number and types of problems that occurred in relation to the benefit obtained. Twenty-six percent of the patients had a change in their cardiorespiratory therapy and their conditions were improved after the pressure data were obtained. Many technical and interpretative problems that tended to decrease the desirability of using pulmonary artery pressure monitoring were identified. Most problems could be avoided by carefully calibrating the monitor system, clearing the catheter system of air bubbles and blood clots, learning to property interpret pulmonary artery pressure tracings despite large respiratory variations, and obtaining a hard-copy printout of the pressure tracing with the simultaneous ECG signal. A protocol for avoiding many difficulties was developed.

Blood Pressure↗

Effect of lung inflation and hypoxia on pulmonary arterial blood volume.

Isolated cat lungs were perfused with constant blood flow. During control conditions (Pa02, 100 Torr), pulmonary artery pressure increased as the lungs were inflated. Hypoxia (Pa02, 22 Torr) increased arterial pressure. However, as the lungs were inflated arterial pressure fell. Thus, the magnitude of the hypoxic pressor response was reduced by inflation. During control conditions, arterial volume (ether bolus method) increased with increasing transpulmonary pressure. Hypoxia decreased arterial volume, and the increase in arterial volume with inflation was somewhat less than that during control conditions. When the influences of vascular and transpulmonary pressures were examined independently by changing one while holding the other constant, increasing transpulmonary pressure increased arterial volume beyond that which could be accounted for by changes in the differences between arterial and pleural pressure. However, this influence of transpulmonary pressure did not appear to be altered by hypoxia. Thus, while hypoxia decreased arterial volume at all levels of lung inflation, it had relatively little effect on the influence of interdependence between the pulmonary arterial bed and the surrounding lung tissue.

Animals↗