Whole-body magnetic resonance imaging in myxoid liposarcoma: A useful adjunct for the detection of extra-pulmonary metastatic disease.

Myxoid liposarcomas (MLS) are a subgroup of soft-tissue sarcomas which have a propensity for extra-pulmonary metastases. Conventional radiological staging of soft-tissue sarcomas consists of chest radiographs (CXR) and thoracic computed tomography (CT) for possible chest metastases, supplemented by magnetic resonance imaging (MRI) for local disease. The optimal radiological modality to detect extra-pulmonary metastases for systemic staging has not been proven. We reviewed the efficacy of Whole-Body MRI (WBMRI) for this purpose. 33 WBMRI and simultaneous CT scans were performed in 28 patients suffering from MLS between 2007 and 2015. 38 metastases were identified in seven patients via WBMRI. Osseous lesions predominated (spine, pelvis, chest-wall and long bones), followed by soft-tissue and abdominal lesions. Of the 29 soft-tissue or osseous metastases that were within the field-of-view of the simultaneous CT scans, five soft-tissue and zero osseous metastases were identified using CT. Metastatic disease was detected in three patients solely using WBMRI, which directly influenced their management. WBMRI is a useful adjunct in the detection of extra-pulmonary metastatic disease, which directly alters patient management. WBMRI has demonstrated an ability to identify more sites of metastatic disease compared to CT. WBMRI should be used in two situations. Firstly, at diagnosis where ablative treatment will be required e.g. amputation, when the diagnosis of occult metastasis would change treatment planning. Secondly, at diagnosis of relapse to confirm if it is a solitary site of relapse prior to consideration of metastectomy.

Oral lichen planus: patient profile, disease progression and treatment responses.

BACKGROUND: Oral lichen planus, or OLP, is a common mucocutaneous immunological disease. The objective of this study was to describe the patient profile, disease progression and treatment responses. METHODS: The authors conducted a retrospective, descriptive study using information from patient records at a tertiary referral center. The study included 229 patients with OLP who were seen in the oral medicine clinic at the University of California, San Francisco, between September 1996 and August 2000, for the first time or for a follow-up visit. Signs and symptoms at various clinic visits were quantified. Responses to treatment and disease progression were determined by comparing scores with baseline scores. RESULTS: The mean age at onset of the disease was 55 years, and 154 (67 percent) of the patients were female. Symptoms generally correlated directly with the severity of OLP forms, which ranged from reticular to erosive. Corticosteroids were effective in reducing symptoms, healing ulcers and reducing erythema. At last follow-up, 65 percent of the patients had the same type of OLP seen initially or the disease had progressed to a more severe type, while 35 percent of patients had less-severe forms than that seen at the initial visit. Four patients (1.7 percent) developed oral squamous-cell carcinoma during the follow-up period. CONCLUSIONS: OLP is a chronic disease with no known cure. Symptoms can improve with corticosteroids; however, the lack of long-term (that is, lifetime) treatment compliance and the adverse side effects of the drugs limit optimal results. CLINICAL IMPLICATIONS: Patients with OLP should be treated if symptoms are significant. Follow-up--including supervision of medication use and monitoring of side effects, as well as periodic examinations for possible malignant transformation--is necessary.

Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival.

The precise staging of hepatocellular carcinoma (HCC) based on the size and number of lesions that predict recurrence after orthotopic liver transplantation (OLT) has not been clearly established. We therefore analyzed the outcome of 70 consecutive patients with cirrhosis and HCC who underwent OLT over a 12-year period at our institution. Pathologic tumor staging of the explanted liver was based on the American Tumor Study Group modified Tumor-Node-Metastases (TNM) Staging Classification. Tumor recurrence occurred in 11.4% of patients after OLT. The Kaplan-Meier survival rates at 1 and 5 years were 91.3% and 72.4%, respectively, for patients with pT1 or pT2 HCC; and 82.4% and 74.1%, respectively, for pT3 tumors (P =.87). Patients with pT4 tumors, however, had a significantly worse 1-year survival of 33.3% (P =.0001). An alpha-fetoprotein (AFP) level > 1,000 ng/mL, total tumor diameter > 8 cm, age > or = 55 years and poorly differentiated histologic grade were also significant predictors for reduced survival in univariate analysis. Only pT4 stage and total tumor diameter remained statistically significant in multivariate analysis. Patients with HCC meeting the following criteria: solitary tumor < or = 6.5 cm, or < or = 3 nodules with the largest lesion < or = 4.5 cm and total tumor diameter < or = 8 cm, had survival rates of 90% and 75.2%, at 1 and 5 years, respectively, after OLT versus a 50% 1-year survival for patients with tumors exceeding these limits (P =.0005). We conclude that the current criteria for OLT based on tumor size may be modestly expanded while still preserving excellent survival after OLT.

Subcutaneous perfusion and oxygen during acute severe isovolemic hemodilution in healthy volunteers.

HYPOTHESIS: Acute severe isovolemic anemia (to a hemoglobin [Hb] concentration of 50 g/L) does not decrease subcutaneous wound tissue oxygen tension (PsqO(2)). SETTING: University hospital operating room and inpatient general clinical research center ward. SUBJECTS: Twenty-five healthy, paid volunteers. METHODS: Subcutaneous oxygen tension and subcutaneous temperature (Tsq) were measured continuously during isovolemic hemodilution to an Hb level of 50 g/L. In 14 volunteers (initially well-perfused), "normal" perfusion (Tsq >34.4 degrees C) was achieved by hydration and systemic warming prior to starting isovolemic hemodilution, while in 11 volunteers (perfusion not controlled [PNC]), no attempt was made to control perfusion prior to hemodilution. MAIN OUTCOME MEASURES: Measurements of PsqO(2), Tsq, and relative subcutaneous blood flow (flow index). RESULTS: While PsqO(2), Tsq, and flow index were significantly lower in PNC vs well-perfused subjects at baseline, there was no significant difference between them at the Hb of 50 g/L (nadir). Subcutaneous PO(2) did not decrease significantly in either group. Arterial PO(2) was not different between the groups, and did not change significantly over time; Tsq and flow index increased significantly from baseline to nadir Hb in both groups. CONCLUSIONS: The level of PsqO(2) was maintained at baseline levels during hemodilution to Hb 50 g/L in healthy volunteers, whether they were initially well-perfused or mildly underperfused peripherally. Given the significant increase in Tsq and flow index, this resulted from a compensatory increase in subcutaneous blood flow sufficient to maintain oxygen delivery. Wound healing depends to a large extent on tissue oxygen delivery, and these data suggest that even severe anemia by itself would not be sufficient to impair wound healing. Thus, transfusion of autologous packed red blood cells solely to improve healing in surgical patients with no other indication for transfusion is not supported by these results.

Acute severe isovolemic anemia impairs cognitive function and memory in humans.

BACKGROUND: Erythrocytes are transfused to prevent or treat inadequate oxygen delivery resulting from insufficient hemoglobin concentration. Previous studies failed to find evidence of inadequate systemic oxygen delivery at a hemoglobin concentration of 5 g/dl. However, in those studies, sensitive, specific measures of critical organ function were not used. This study tested the hypothesis that acute severe decreases of hemoglobin concentration alters human cognitive function. METHODS: Nine healthy volunteers, age 29 +/- 5 yr (mean +/- SD), were tested with verbal memory and standard, computerized neuropsychologic tests before and after acute isovolemic reduction of their hemoglobin to 7, 6, and 5 g/dl and again after transfusion of their autologous erythrocytes to return their hemoglobin concentration to 7 g/dl. To control for duration of the experiment, each volunteer also completed the same tests on a separate day, without alteration of hemoglobin, at times of the day approximately equivalent to those on the experimental day. RESULTS: No test showed any change in reaction time or error rate at hemoglobin concentration of 7 g/dl compared with the data at the baseline hemoglobin concentration of 14 g/dl. Reaction time, but not error rate, for horizontal addition and digit-symbol substitution test (DSST) increased at hemoglobin 6 g/dl (mean horizontal addition, 19%; 95% confidence interval [CI], 4-34%; mean DSST, 10%; 95% CI, 4-17%) and further at 5 g/dl (mean horizontal addition, 43%; 95% CI, 6-79%; mean DSST, 18%; 95% CI, 4-31%). Immediate and delayed memory was degraded at hemoglobin 5 g/dl but not at 6 g/dl. Return of hemoglobin to 7 g/dl returned all tests to baseline, except for the DSST, which significantly improved, and returned to baseline the following morning after transfusion of all autologous erythrocytes. CONCLUSION: Acute reduction of hemoglobin concentration to 7 g/dl does not produce detectable changes in human cognitive function. Further reduction of hemoglobin level to 6 and 5 g/dl produces subtle, reversible increases in reaction time and impaired immediate and delayed memory. These are the first prospective data to demonstrate subtle degraded human function with acute anemia of hemoglobin concentrations of 6 and 5 g/dl. This reversibility of these decrements with erythrocyte transfusion suggests that our model can be used to test the efficacy of erythrocytes, oxygen therapeutics, or other treatments for acute anemia.

Formation of 8-hydroxydeoxyguanosine, hydroxyl free radical adduct of DNA in granulocytes exposed to the tumor promoter, tetradecanoylphorbolacetate.

The exposure of human granulocytes to the tumor promoter, tetradecanoylphorbolacetate (TPA), resulted in the accumulation of 8-hydroxydeoxyguanosine (8-OHdG) in the DNA of the treated cells. Hydroxyl free radicals react with DNA causing the hydroxylation of guanine at the C-8 position. The modified nucleoside (8-OHdG) cleaved from DNA, was quantitated at subpicomole levels utilizing high pressure liquid chromatography with electrochemical detection (LCED). Superoxide dismutase and catalase caused a marked decrease in the levels of 8-OHdG in the cellular DNA. The level of 8-OHdG formed by TPA stimulation of granulocytes was equivalent to one modified guanine for about every 600 possible guanines in the cellular DNA.

Hydroxyl free radical adduct of deoxyguanosine: sensitive detection and mechanisms of formation.

DNA or 2-deoxyguanosine reacts with hydroxyl free radical to form 8-hydroxy-deoxyguanosine (8-OH-dG). We found that 8-OH-dG can be effectively separated from deoxyguanosine by high pressure liquid chromatography and very sensitively detected using electrochemical detection. The sensitivity of electrochemical detection is about one-thousand fold enhanced over optical detection. Utilizing deoxyguanosine in bicarbonate buffer it was found that ferrous ion, but not ferric ion, was effective in forming 8-OH-dG. The hydroxyl free radical scavenging agents, thiourea and ethanol, were very effective in quenching Fe(11) mediated 8-OH-dG formation, but superoxide dismutase had very little effect.

Use of salicylate with high pressure liquid chromatography and electrochemical detection (LCED) as a sensitive measure of hydroxyl free radicals in adriamycin treated rats.

Hydroxyl free radicals react with salicylate to form 2,3-dihydroxybenzoic acid (2,3-DHBA) and 2,5-dihydroxybenzoic acid (2,5-DHBA). Utilizing the technique of high pressure liquid chromatography with electrochemical detection (LCED), it is possible to detect DHBAs at the level of femtomoles. Since salicylate is relatively non-toxic, we have administered it as a trapping agent in a first attempt to examine the use of the LCED method as a sensitive measure of in vivo OH production. Utilizing adriamycin administration as a model to induce oxygen free radical tissue damage, we found that the level of DHBAs present in drug treated rats versus controls was increased 100-fold in heart and muscle, 30-fold in lung, and 3- and 4-fold in brain and blood, respectively. These first observations support the theory that adriamycin induces OH in tissue and indicates that the LCED method may prove to be useful to measure oxygen free radical production in vivo.

Sensitive assay of hydroxyl free radical formation utilizing high pressure liquid chromatography with electrochemical detection of phenol and salicylate hydroxylation products.

Evidence is presented for a sensitive method useful for the detection of hydroxyl free radical generation in various systems. The methodology employs high pressure liquid chromatography with electrochemical detection (LCED) for the quantification and identification of the hydroxylation products from the reaction of OH with both phenol and salicylate. A detection limit of less than 1 pmol for the hydroxylation products has been achieved with electrochemical detector responses linear over at least three orders of magnitude. Detection and quantitation of the hydroxylation products obtained and formed during OH generation from biologically meaningful systems have been demonstrated. The three systems utilized were ADP/FE(II)/H2O/, hypoxanthine/xanthine oxidase plus chelated iron, and UV photolysis of H2O2.

Purification of a new high activity form of glucose-6-phosphate dehydrogenase from rat liver and the effect of enzyme inactivation on its immunochemical reactivity.

A new form of cytoplasmic glucose-6-phosphate dehydrogenase (E.C.1.1.1.49) was purified from rat liver by protamine sulfate precipitation, ammonium sulfate fractionation, ion exchange chromatography with diethylaminoethyl cellulose, and affinity chromatography with Cibacron blue agarose and NADP agarose. This form of the enzyme has a specific activity of over 600 units/mg of protein and gives essentially a single band by polyacrylamide gel electrophoresis. The form of the enzyme isolated by this purification method is 3 times more active than the form purified from liver by previously reported procedures. The relative mass of this pure glucose-6-phosphate dehydrogenase enzyme was determined by disc gel electrophoresis to be 269,000. This high activity glucose-6-phosphate dehydrogenase enzyme, after inactivation by reaction with palmityl-CoA, was no longer precipitated by specific rabbit and goat antisera to this purified enzyme. Thus, the possibility still exists that starved fat-refed animals contain glucose-6-phosphate dehydrogenase (G6PD) enzyme protein in an inactivated form no longer detectable by either enzyme activity or immunoprecipitation.

Hemolysins of Edwardsiella tarda.

Isolates of Edwardsiella tarda from four sources produced nonfilterable hemolsin in trypticase soy broth. The cell-associated hemolysin was partially heat labile, destroyed by formalin and sensitive to treatment with trypsin. These characteristics, and the observation that Ca++ or Mg++ ions enhanced activity, suggest that a proteinaceous, enzymic component may be responsible for the hemolytic activity.

Dental learning resources center.

The University of Kentucky College of Dentistry has been operating the Dental Sciences Study Center since 1971 to support a curriculum with a large percentage of individualized instruction. Three crucial aspects of the Study Center were discussed: the facilities, the instructional materials, and the atmosphere. Administrative attention to and support of each aspect are essential to the successful functioning of a learning resources center in a largely individualized dental curriculum.

Edwardsiella tarda infections in Florida racoons, Procyon lotor.

Edwardsiella tarda was isolated from the large intestine of seven (17%) of 42 racoons from Florida. The rate varied from 12% in South Florida to 25% in North Florida. In addition, 52% of the racoons examined were carrying Salmonella, with numerous serotypes represented.

Effect of dietary fat and sucrose on the activities of several rat hepatic enzymes and their diurnal response to a meal.

Regulation of the cytoplasmic enzymes, pyruvate kinase (PK), glucokinase (GK), phosphoenolpy ruvate carboxykinase (PEPCK), fructose-1,6-diphosphatase (FDP), ATP citrate-lyase (ATP-CL), NAD-malate dehydrogenase (NAD-MD), NADP-malate dehydrogenase (NADP-MD), glutamic-pyruvic transaminase (GPT), glucose-6-phosphate dehydrogenase (G6PD), and 6-phosphogluconate dehydrogenase (6PGD), in rat liver by dietary fat (F diet) and dietary sucrose (S diet) was investigated. Mealfeeding the S diet to adult rats for 5 and 9 months resulted in a diurnal dietary response (i.e., food response) variation of FDP, GK, ATP-CL, 6PGD, and PK, while meal-feeding the S diet to young rats resulted in diurnal dietary response variation of ATP-CL, G6PD, NADP-MD, 6PGD, GPT, and PK. Meal-feeding the fat diet results in essentially no diurnal variation in enzyme activity. The overall effect of meal-feeding, as compared with ad libitum feeding, of the S diet was to increase the levels of G6PD, ATP-CL, and NADP-MD and to decrease the level of PEck in the meal-fed rats. Young rats meal-fed the two diets have higher enzyme activities than meal-fed adult rats for the observed enzymes (except for GPT and NAD-MD). In general, hepatic levels of the enzymes studied are low in the F diet-fed animals and markedly higher for the S diet-fed animals. These results suggest that dietary carbohydrate specifically induces those enzymes involved in carbohydrate metabolism, whereas dietary fat does not affect their levels. On the basis of prior evidence for an early requirement of RNA synthesis for sucrose induction of G6PD, this widespread induction of liver enzymes by carbohydrate must indicate either increased synthesis of ribosomal RNA with later regulation of synthesis specifically of these enzymes or increased synthesis of a rather large group of specific messenger RNAs i.e., coordinate genetic control of a number of these enzyme messenger RNAs.

Regulation of glucose-6 phosphate dehydrogenase and 6-phosphogluconate dehydrogenase in the meal-fed rat.

Meal-feeding of a high sucrose diet produces a diurnal cycle (i.e., food response) in glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) levels resulting in an elevated level of these enzymes at approximately 12 hours after the start of a 2-hour meal and a return to base level by 24 hours. The effects of actinomycin D and cycloheximide on the 12-hour increases in G6PD and 6GPD were determined. Cycloheximide completely blocked the increase in G6PD if administered 2 or 4 hours after start of the meal, while actinomycin D completely blocked the increase in G6PD if administered at 2 hours and almost completely at 4 hours after start of the meal. These results were obtained previously with starved rats refed a sucrose diet. The diurnal increases in G6PD and 6PGD in meal-fed rats and the induction of G6PD in starved-refed rats thus appear to be regulated by the same mechanism requires RNA synthesis within 4 hours after start of re-feeding. The response of 6PGD to cycloheximide and to actinomycin D at 2 or 4 hours after start of the meal is essentially the same as that of G6PD. These data suggest that the increases in G6PD and 6PGD (and other enzymes) brought about by carbohydrate refeeding AFTER starvation or by carbohydrate meal-feeding on a diurnal cycle are mediated by a rapid change in RNA synthesis. This appears most compatible with a coordinate control of gene expression through messenger RNA synthesis.