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Biomedical subjects

W S Blakemore

Publications and source records attributed to W S Blakemore.

At least 37 records · Page 2Linked to original sources
PubMed1989

The content of tumor DNA as an indicator of prognosis in patients with T1N0M0 and T2N0M0 carcinoma of the breast.

To determine if the flow cytometric measurement of the content of the tumor DNA could provide prognostic information in T1N0M0 and T2N0M0 carcinoma of the breast, we isolated nuclei from paraffin-embedded tumor specimens from 128 consecutive patients who underwent modified radical mastectomy and were found to have a T1 or T2N0M0 carcinoma of the breast. The content of DNA of the nuclei was determined by flow cytometry. Although the average tumor size was not significantly different, 17 of 56 patients with aneuploid tumors died of cancer compared with 2 of 72 with euploid tumors. The 10-year overall actuarial survival rate of the euploid and aneuploid groups was 72% and 67%, respectively (p less than 0.02). A hazards model of the data shows that the DNA content of the tumor is the most significant indicator of prognosis, with a 2.25-fold increased risk of death for patients with aneuploid tumors. These data show that the tumor DNA content can be used to identify a group of patients with T1 or T2N0M0 carcinoma of the breast with the same prognosis as a group of patients without carcinoma of the breast that would be unlikely to benefit from adjuvant therapy.

Adult↗
PubMed1988

Validity of 3-methylhistidine excretion as an indicator of skeletal muscle protein breakdown in humans.

The urinary excretion of 3-methylhistidine (3MEH) in humans and animals has been used as a biologic marker for skeletal muscle protein breakdown. In rats, it has been recently suggested that there is a significant contribution of 3MEH in urine from the gastrointestinal tract due to the rapid turnover of protein in that tissue. To evaluate this point in humans, six patients with short bowel were evaluated. They were placed on three-day meat-free diets while 24-hour urine collections were obtained. The mean +/- SEM 3MEH in the short-bowel group was 3.27 +/- 0.34 mumol/kg/d and the mean +/- SEM molar ratio of 3MEH to creatinine was 0.0212 +/- 0.0012. These data were not significantly different from the control group at 95% confidence level. The results suggest that the contribution of the small intestine appears to be negligible, therefore urinary 3MEH should continue to be a valid index of skeletal muscle breakdown in man.

Adult↗
PubMed1987

Effect of adriamycin on heart mitochondrial DNA.

The effect of Adriamycin on rat heart mitochondrial DNA was determined by initially labelling the DNA with [Me-14C]thymidine. Animals subsequently received intravenously either Adriamycin (10 mg/kg) or saline (1 ml/kg) (control group). Animals later received [Me-3H]thymidine and were killed at 6, 14, 24 and 36 h after this. The heart mitochondrial DNA was separated into the linear, non-supercoiled and supercoiled forms by ultracentrifugation on formamide/sucrose sedimentation gradients, and the amount of 14C and 3H incorporated into the various forms of the DNA was determined by scintillation counting. The data suggest that Adriamycin may cause breakage of the mitochondrial DNA helix, and that it slows the rate of mitochondrial DNA synthesis and the formation of complete DNA molecules. These experiments show that Adriamycin does interact with heart mitochondrial DNA, and may explain the cardiac dysfunction association with Adriamycin use.

Animals↗
PubMed1985

Truncus arteriosus with interrupted aortic arch: report of a successful surgical repair.

The association of truncus arteriosus with interrupted aortic arch represents a formidable surgical challenge. Two successful repairs have been reported, but none for the past ten years. This report presents a third successful repair using a technique that allows the widely patent ductus arteriosus to maintain continuity between the truncus (with pulmonary arteries detached) and the descending aorta. Right ventricle-pulmonary artery continuity is established in the usual way with a porcine-valved conduit. While long-term potential difficulties with this approach are recognized, it appears to give satisfactory initial palliation and to be an acceptable method of treatment for this combination of defects. The embryology and the anatomy of the lesion are briefly discussed.

Aorta, Thoracic↗
PubMed1985

Technical evaluation of factors interfering in the carcinoembryonic antigen assay.

Storage of serum or plasma at room temperature (RT) or 4 degrees C for eight days did not alter the level of carcinoembryonic antigen (CEA). However, storage of whole blood at RT for 8 days resulted in false elevated CEA levels compared to controls. Heating of serum or plasma at 56 degrees C for 30 min or freezing and thawing for fifteen times did not change the CEA levels in these specimens. Comparison of CEA levels in the serum and plasma of the same specimens showed significantly higher levels of CEA in plasma than serum specimens. Collection of blood in tubes with different anticoagulants showed significantly false elevated levels of CEA only when blood was collected in heparinized tubes. These data indicate the importance of knowing the factors interfering in the CEA assay when interpreting its results.

Blood Preservation↗
PubMed1984

The effect of major thermal injury and carbohydrate-free intake on serum triglycerides, insulin, and 3-methylhistidine excretion.

The severely burned patient responds differently to starvation ketosis in the early stage of injury as compared to the normal individual. A similar response has been observed in the patient after skeletal trauma and sepsis. In order to determine the extent of muscle protein contribution and the mechanism(s) involved, 11 burn patients with 35% to 80% BSA burn were resuscitated using carbohydrate-free solutions for 3 days followed by unrestricted intake. Blood was drawn daily and 24-hour urinary nitrogens were determined. Controls consisted of 10 preoperative elective surgical patients and two normal volunteers. The burned patients lost a mean +/- SEM of 17.1 +/- 1.72 g nitrogen per day on the third day. The mean +/- SEM ketone body response on the third day for burned patients was 385 +/- 77 mumol/l compared to 727 +/- 81 mumol/l for control patients. The mean +/- SEM 3-methylhistidine loss for burned patients on the third day was 9.83 +/- 0.82 mumol/kg compared to 3.6 mol/kg for control patients. Insulin levels on the third day of fast were three times the normal group. This insulin increase may be the modulating factor that suppresses excessive fat mobilization. This metabolic response causes a lower plasma ketone level, which may then necessitate the need for continued protein catabolism for glucose production for certain tissues. The protein contribution to the hypercatabolic response as assessed by increased urinary nitrogen losses is in part supported by an increased muscle protein breakdown as indicated by increased 3-methylhistidine excretion.

Adult↗
PubMed1983

Rapidly progressive proptosis secondary to Burkitt's lymphoma. Origin in the ethmoidal sinuses.

A case of unilateral proptosis secondary to Burkitt's lymphoma occurred in the ethmoidal sinuses. Involvement of the skull and paranasal sinuses by Burkitt's lymphoma may masquerade initially as an infectious process delaying diagnosis and treatment. The tumor's rapid growth and dramatic response to therapy with the potential for long-term remission and cure emphasize the need for prompt diagnosis and treatment.

Burkitt Lymphoma↗
PubMed1983

Evaluation of whole body nitrogen kinetics in acute metabolic acidosis.

The data obtained after a pulse dose of L-[15N] alanine and [13C] urea in control and acidotic conscious dogs were analyzed to compute the whole body nitrogen turnover rates. Acute acidosis was induced and maintained by continuous HCl infusion. On the basis of a four pool model, the mean daily protein synthesis rate in the normal dog was calculated to be 10.8 g/kg compared to 7.6 g/kg in acidosis. Since all dogs were in negative nitrogen balance, the daily catabolic rate of protein was greater than the synthetic rate and the mean daily catabolic rate was 14.4 g protein/kg in normal dogs compared to 10.5 g protein/kg in acidotic dogs. The body urea pool size and excretion rates were decreased by 24 and 27%, respectively, due to acute acidosis, without any change in the fractional turnover rate. Thus the adaptive response to the induced acid challenge appears to be a reduction in the synthesis and breakdown rates of protein and also a decrease in the production and excretion rate of urea.

Acidosis↗
PubMed1982

Net metabolic changes of zinc, copper, nitrogen, and potassium balances in skeletal trauma patients.

Zinc, copper, nitrogen, and potassium balances of 10 male skeletal trauma patients were determined over 5-6 days each. Nutrition consisted of electrolyte/glucose and/or blood/blood product infusions. Patients were started on balance studies within 24 hr following injury. Zinc and copper were analyzed by atomic absorption while nitrogen was measured by the microKjeldahl technique and potassium by flame photometry. The mean daily balances for these patients were -1563 micrograms zinc, -266 micrograms copper, -20.0 g nitrogen and -29 mEq potassium for 5 patients receiving electrolyte/glucose infusions and +1273 micrograms zinc, +322 micrograms copper, -12.9 g nitrogen, and -26 mEq potassium for 5 patients receiving blood/blood products in addition to electrolyte/glucose. Routine daily maintenance supplementation of 2 mg zinc and 2 mg copper is recommended for skeletal trauma patients on electrolyte/glucose and those on electrolyte/glucose with blood/blood products intravenous infusions. Further balance studies are necessary to ascertain the level of zinc and copper supplementation needed by skeletal trauma patients receiving different nutritional support.

Adolescent↗
PubMed1982

Comparison between in vitro lymphocyte activity and metabolic changes in trauma patients.

This study was designed to investigate the relationship of in vitro and in vivo components of host immunocompetence and various biochemical parameters of injury. Thirteen multiple trauma victims were evaluated within 2 to 3 days postinjury while maintained on 5% glucose. The mean nitrogen balance of the patients was -18 gm/24 hr and the resting metabolic expenditure was increased 22.3%. Seventy-five per cent of the patients skin tested were anergic or relatively anergic. Patient lymphocyte response to the T cell mitogens phytohemagglutinin and concanavalin A were suppressed 45 and 48%, respectively, when compared to 24 normal healthy individuals. Total lymphocyte count (1,558) and percentage of T lymphocytes (63%) were within normal limits. The suppression of lymphocyte response to mitogens correlated by regression analysis with the negative nitrogen balances and resting metabolic expenditures in these patients (p less than 0.05). The depression of lymphocyte activity can be correlated with the catabolic response of injury in multiple trauma patients.

Adolescent↗
PubMed1981

Urinary excretion of 3-methylhistidine: an assessment of muscle protein catabolism in adult normal subjects and during malnutrition, sepsis, and skeletal trauma.

The urinary excretion of 3-methylhistidine (3 MEH) has been shown to be a reliable index of muscle protein breakdown. It is decreased in protein-calorie malnutrition and increased during the hypercatabolic phase of sepsis and thermal trauma. Losses of 3 MEH after moderate to severe skeletal trauma in man and animals are reported as increased or unchanged. To clarify this response, 24 male and 6 female skeletal trauma patients were evaluated for 24 hr urinary losses of 3 MEH, nitrogen and creatinine. Eight of the 24 males also received a catabolic steroid for treatment of a head injury. In addition, 3 male and 1 female septic patients were similarly evaluated. Controls consisted of 10 volunteers on a meat free diet for 4 days and of 8 volunteers who were given only intravenous 5% dextrose in water for 3 days. The 3 MEH excretion for all control males was 3.6 mumole/Kg/day and for females was 2.8 Skeletal trauma produced a 280% increase for the males and a 225% increase for the females. Trauma with steroids caused a 325% increase. Sepsis induced a 227% increase in 3 MEH losses for males and 292% for females during the febrile episode. Creatinine excretion also increased significantly in response to trauma and sepsis but the magnitude of the increase was less than for 3 MEH. This was reflected in the 3 MEH to creatinine molar ratio increase from 0.018 for controls to 0.030-0.040 in sepsis and trauma. Patients with extensive body weight loss showed decreases in 3 MEH and creatinine excretion and a molar ratio similar to controls. The calculated contribution of muscle protein to whole body protein breakdown in the trauma and septic groups showed a twofold increase compared to the control group. The data indicate that the increased muscle protein catabolic response following stress of skeletal trauma and sepsis provides an insight on the origin of the large urinary nitrogen losses following such insults.

Adolescent↗
PubMed1981

Contribution of skeletal muscle protein in elevated rates of whole body protein catabolism in trauma patients.

Whole body protein breakdown using 15N and skeletal muscle protein breakdown from urinary 3-methylhistidine were measured simultaneously in seven skeletal trauma and eight normal subjects on a standard hypocaloric, protein free diet. The trauma group had a 31% greater resting metabolic energy expenditure than controls. The control males lost 3.73 mumol/kg/day of 3-methylhistidine which suggested a protein breakdown rate of 0.89 g P/kg/day. The control females lost 2.46 mumol/kg/day of 3-methylhistidine or a breakdown rate of 0.58 g P/kg/day. These parameters were 187% greater for males and 163% greater for females in the trauma group. The measured whole body protein breakdown rates were 3.64 g P/kg/day for the control males and 2.69 for females. Skeletal trauma increased both by 73%. Skeletal trauma raised the muscle contribution to the whole body breakdown rate from 24.4 to 40.4% for men and from 21.6 to 33.0% for women. This disproportionate increase in muscle protein breakdown is consistent with muscle protein metabolism being most seriously affected by severe injury.

Adult↗
PubMed1981

A comparison of the effects of skeletal trauma and surgery on the ketosis of starvation in man.

The increase of plasma ketone bodies (acetoacetic acid and beta-hydroxybutyric acid) is related to the efficient protein-sparing adaptation during a total fast by healthy man. This study investigated the response to a total fast during the postinjury state. Twenty patients with skeletal or soft-tissue trauma received 3 days of carbohydrate-free intake and then 3 more days of carbohydrate intake. Control subjects were ten postoperative patients and two healthy volunteers who received similar nutritional treatment. The trauma patients lost nearly 20 gm of nitrogen/day, which was twice control, and had a resting energy expenditure of 27.07 kcal/kg, 21.4% greater than controls. Trauma was found related to an elevation in plasma glucose and to inhibit the rise in plasma ketone bodies and free fatty acids. In contrast, indirect calorimetry showed that fat contributed 63% of the nonprotein energy on the third day of fasting and injury. These data indicate that fat is utilized by the trauma patient but that fatty metabolism is abnormal compared to starvation in healthy or mildly stressed patients.

Acetoacetates↗
PubMed1981

Whole-body protein metabolism due to trauma in man as estimated by L-[15N]alanine.

Changes in whole-body protein metabolism due to several skeletal trauma were estimated in five male volunteers and four male trauma patients using a single pulse of [15N]alanine and [13C]urea. The isotopic decay data were computer curve-fitted to obtain the best estimates for eight parameters of a four-pool model. The trauma patients excreted almost 5 times as much urinary nitrogen and utilized 33% more energy than did the volunteers on the same hypocaloric, protein-free diet. Trauma was found to expand the "active metabolic nitrogen" pool and the transfer rates of nitrogen into and out of a "slow turnover protein" pool. Whole-body protein synthesis increased 37% above normal and protein breakdown increased 79% above normal due to trauma. These values were in agreement with those determined at the same time using a [14C]leucine continuous infusion method. The data show that trauma accelerates the nitrogen flow and both protein synthesis and breakdown. This mechanism for negative nitrogen balance is consistent with that found for other severe stresses but is different from milder stresses.

Alanine↗
PubMed1980

Comparison of the carcinoembryonic antigen levels by dialysis and sephadex column methods.

Duplicate plasma samples from 64 human donors were tested and compared for the levels of carcinoembryonic antigen (CEA) by the conventional dialysis and sephadex column methods. Results from the column method were similar to those from the dialysis method, with a correlation coefficient of 0.9959. In addition, the assay time by the sephadex column was only four to five hours, as compared with 18 to 24 hours for the dialysis procedure. The potential usefulness in substituting the sephadex column for the dialysis method in CEA determinations is discussed.

Carcinoembryonic Antigen↗
PubMed1980

Effects of major skeletal trauma on whole body protein turnover in man measured by L-[1,14C]-leucine.

Skeletal trauma induces excessive urinary nitrogen losses and is thought to stimulate the oxidation of the branched chain amino acids. This study was undertaken to quantitate whole body protein turnover rates and leucine metabolism during the peak nitrogen loss period following skeletal trauma. Quantitation was done in eight healthy and six trauma subjects, who received D5W as their only nutrition for 72 hours, using a 10-hour continuous infusion of L-[1,14C]-Leucine. The controls lost an average of 6 gm of nitrogen/day and the trauma patients 25 gm of nitrogen/day on the study day. Trauma was shown to elevate plasma leucine by 76%, increase the leucine flux through the free leucine pool by 86%, and accelerate leucine oxidation by 277% over the values for controls. Trauma also produced a 50% increase in whole body protein synthesis and a 79% increase in protein breakdown. The data clearly define significant increases in both the protein synthetic and catabolic rates in trauma with a greater increase occurring in catabolism. This is similar to findings for protein turnover in sepsis and burn injury, but is different from that found in elective surgery. A striking aspect of our data is the indication that women do not exhibit the same response to injury that men do. This suggestion, however, is based on a small sample.

Adult↗