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Biomedical subjects

W S Blakemore

Publications and source records attributed to W S Blakemore.

At least 19 recordsLinked to original sources

Protein C activity, stage of disease, and vascular thrombosis in colon carcinoma.

To determine the etiology of the increased incidence of postoperative deep venous thrombosis (DVT) in patients with carcinoma of the colon, serum levels of protein C were measured preoperatively in 65 patients with colorectal adenocarcinoma. Noninvasive lower-extremity Doppler studies were performed on all patients prior to discharge to assess patency of the deep veins. Six patients (9%) were found to have DVT. The protein C level was considered elevated if it was greater than 125% of control values and reduced if less than 75% of control values. The development of DVT was found to be independent of the serum carcinoembryonic antigen, albumin, total protein, hemoglobin, hematocrit, platelet count, prothrombin time, partial thromboplastin time, and the patient's age and percentage of ideal body weight. There was an inverse relationship between the protein C level (p less than 0.001), Dukes stage of the tumor (p less than 0.001), and the development of DVT. Linear regression analysis revealed that only the tumor stage and the protein C level could be used to predict the development of DVT. The data show that for these patients with colorectal malignancy, the development of DVT may be related to decreased levels of protein C.

Adenocarcinoma

Regulation of glucose kinetics in trauma patients by insulin and glucagon.

The current study was undertaken to evaluate the contribution of insulin and glucagon to regulation of glucose metabolism in man following severe, traumatic injury by manipulating concentrations of insulin and glucagon with infusions of somatostatin. Glucose kinetics were assessed with [U-14C, 6-(3)H]glucose in severely injured patients and compared with data obtained from patients recovering from minor, elective operative procedures. Glucose production was significantly increased in subjects with traumatic injury compared with control subjects (13.0 +/- 0.63 mumol/kg/min v 8.6 +/- 0.27 mumol/kg/min). There was no impairment in glucose oxidation by the injured patients. Modulation of insulin and glucagon with somatostatin indicated that non-insulin-mediated glucose uptake (NIMGU) was significantly elevated in injured patients (12.2 +/- 0.94 mumol/kg/min v 7.4 +/- 0.61 mumol/kg/min). Hepatic glucose output (HGO) in the absence of glucagon was also significantly elevated in injured patients (12.2 +/- 1.20 mumol/kg/min v 5.8 +/- 1.08 mumol/kg/min). Indirect calorimetry showed a 27% increase in resting energy expenditure (REE). Increased protein oxidation accounted for 56% of the increase in REE. Changes in carbohydrate and lipid oxidation accounted for 28% and 15% of the increase in REE. There was no correlation between the injury severity score of the injured patient and the degree of metabolic abnormality. It is concluded from these studies that (1) injured patients have a high rate of glucose turnover in the absence of glucagon and insulin; (2) the reliance on glucose as a source of energy is not diminished in injured subjects; and (3) increases in protein oxidation account for the majority of the increased REE found in injured patients.

Adolescent

Plasma amino acid concentrations in geriatric control and hip-fracture patients.

Changes in plasma amino acids, 24-h nitrogen balances, and resting metabolic expenditures (RMEs) were measured in 10 geriatric patients (aged 70-92 y) with hip fracture 1 d after surgical fixation during both a 24-h fasting state and while receiving total peripheral parenteral nutrition (TPPN) for 24 h at 1.5 g amino acids.kg-1.d-1 and 29-30 kcal.kg-1.d-1 and compared with 19 healthy volunteer subjects (aged 70-84 y). RME and 24-h urinary nitrogen losses were also elevated in the trauma patients during both fasting and TPPN. Positive nitrogen balances were evident in both groups during TPPN. Plasma total amino acid concentration was significantly lower in the trauma patients because of lower plasma concentrations of the nonessential amino acids. Phenylalanine and methionine concentrations were significantly higher and lysine lower in the trauma group. In addition, evaluation of the essential amino acid ratios after fasting and TPPN reveal that there are no limiting amino acids during TPPN.

Aged

Effect of deoxyribonucleic acid ploidy status on survival of patients with carcinoma of the endometrium.

This retrospective study was performed to determine the clinical usefulness of deoxyribonucleic acid (DNA) ploidy and the amount of DNA in the nucleus of the tumor cell on the prognosis of patients with carcinoma of the endometrium. Five year follow-up study was obtained for 121 patients. Flow cytometric analysis was used to determine tumor cell ploidy from paraffin-embedded specimens. Patients were grouped according to ploidy, clinical stage and grade and whether or not they received postoperative radiation. The data were subjected to a Cox proportional hazards regression analysis, and only ploidy status and clinical stage were significantly associated with survival time. Of the 121 patients observed, 44.6 per cent were aneuploid and 55.4 per cent, euploid. Preliminary chi-square analysis indicated a strong survival advantage to those patients with euploid endometrial carcinoma. The over-all five year survival rate for patients with aneuploid tumors was 53.7 per cent, as opposed to 80.6 per cent for patients with euploid tumors (p less than 0.01). Eighty-seven patients were Stage I, 39 aneuploid, 48 euploid. The five year survival rate for patients with Stage I aneuploid was 71.8 versus 85.4 per cent for those who were euploid. Twenty-one patients were Stage II; seven aneuploid and 14 euploid. The five year survival rate for aneuploid patients was 14.3 versus 85.7 per cent for euploid patients. The over-all five year survival rate for those with Stage I and II was 85.5 per cent euploid and 63.0 per cent aneuploid, p less than 0.05. Patients with Stage III or IV had poor outcome regardless of ploidy status. These data show that patients with euploid Stage I and II carcinoma of the endometrium have a significant survival advantage over patients with aneuploid tumors. We, therefore, believe that ploidy status may be used to facilitate the determination of prognosis in carcinoma of the endometrium.

Adenocarcinoma

Prognostic applications of DNA analysis in solid malignant lesions in humans.

Analysis of the DNA of tumors using flow cytometry is a technologic method that can be used to investigate the biologic nature of tumors. While not conclusive, results suggest that this biologic information may be useful in identifying patients with malignant disease who have a worse prognosis. The differentiation of patients with aneuploid tumors into those with hypoploid tumors and those whose tumors are hyperploid may be a further refinement of the technique. Also, a combination of this biologic criteria may allow a more accurate selection of patients than either method alone. Further investigative work needs to be done to fully evaluate the clinical usefulness of flow cytometric DNA analysis and answer these and other questions.

Adult

Glucose metabolism and colorectal carcinoma.

We evaluated nine patients with colorectal cancer and six control patients in a postabsorptive state in an attempt to define the effect of cancer on glucose turnover, oxidation, recycling, and resting metabolic expenditures (RME). The glucose kinetics were determined using a double-labeled [U-14C] glucose and [6-3H] glucose, and energy expenditures were measured by indirect calorimetry. In addition, we also measured the same parameters in the cancer patient group on a total parenteral nutrition (TPN)-glucose system on the fourth day before and on the fifth day after removal of tumor. In the postabsorptive state, glucose turnover and oxidation rates were similar in the cancer and control group; however, the mean glucose pool size of the cancer group was 47% larger than the control group and was statistically significant (P = .05). Glucose recycling was also two times the control group and was statistically significant (P = .05). The recycling of glucose, both preoperatively and postoperatively, continued in the face of infused glucose; however, the rate was suppressed compared with the fasting cancer group. Postabsorptive RME of the cancer group did not differ from those predicted by the Harris-Benedict equation. Following a 4-day infusion of TPN-glucose that supplied a mean of two times the patients' energy needs, the preoperative cancer group showed a mean increase in RME of 25.6% and a 31.58% increase on the fifth postoperative day of TPN-glucose, presumably due to increased lipogenesis and to a much lesser extent from the increased protein synthesis (4 g positive N balance).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

A physiologic basis for the provision of fuel mixtures in normal and stressed patients.

It has been suggested that lipid is a preferred fuel in stressed patients. We evaluated glucose oxidation in 20 patients (sepsis, cancer of the colon, multiple trauma, controls) while they received TPN (5.65 mg glucose/kg/min). Respiratory quotient (RQ) was measured by indirect calorimetry and the percent VCO2 arising from the oxidation of glucose was measured using [U-14C] glucose. Since RQs were 1.0 or greater in all patients, the nonprotein energy utilized by them was calculated to be derived completely from glucose. However, the kinetic data showed that glucose contributed only 55-60% of the VCO2. Protein oxidation contributed less than 20% of the VCO2, as calculated from urinary nitrogen. The difference must have been derived from fatty acid oxidation. The glucose turnover that was not oxidized was presumed to be converted to lipid at an RQ of 8.6. The net oxygen consumption and carbon dioxide production from this overall distribution resulted in an RQ of about 1.0 with only 60% coming from glucose oxidation. Since all patients responded in the same manner, it appears that the proper ratio of glucose and lipid was dictated on a physiologic basis and not on the type of disease.

Adult

Abdominal aortic aneurysm and horseshoe kidney. A different perspective.

We report a case of abdominal aortic aneurysm with horseshoe kidney. The anatomic distribution of the renal vessels, the position of the thin portion of the isthmus of the kidney, and concern for the preservation of the sexual potency of the patient made standard aneurysm repair untenable. We describe a method of repair by exclusion of the aneurysm.

Aneurysm

A continuous analyzer for monitoring respiratory gases and expired radioactivity in clinical studies.

A system for the continuous monitoring of gas exchange as well as 14CO2 from metabolic studies is described. The analyzer incorporates modifications over previously published systems. These modifications include accurate control of analyzer pressure for stable baselines during the long periods of measurement, accurate control of temperature, the measurement of oxygen consumption during high oxygen patient therapy, the measurement of oxygen consumption of patients on a mechanical respirator, and describes a unique flux system to calibrate the analyzer detectors. The closed system provides expired breath data for O2, CO2, and 14CO2 on critically ill patients for long periods of time without stressing the patient and without using a face mask or mouthpiece. These data allow for the calculation of daily energy expenditures of hypermetabolic patients and for the assessment of various metabolic responses with 14C substrates.

Calorimetry

Circulating immune complexes in human osteosarcoma.

Sera from 8 patients with osteosarcoma and 64 normal individuals were examined by C1q and Raji cell radioimmunoassays for the presence of circulating immune complexes. Of the 8 patients with osteosarcoma, 6 had elevated levels of immune complexes in their sera. The elevated levels of immune complexes were demonstrated by both the C1q radioimmunoassay and the Raji cell radioimmunoassay. The amount of immune complexes was quantitated by Raji cell radioimmunoassay; the mean plus or minus the standard error of the amount of aggregated human IgG equivalent per milliliter of serum was 80.12+/-72.64 micrograms for patients with osteosarcoma and 23.07+/-6.2 micrograms for normal individuals. The blocking effect of sera from patients with osteosarcoma on lymphocyte cytotoxicity against cultured osteosarcoma cells (TE-85) was examined. The result indicated that sera with elevated amounts of immune complexes also had increased levels of blocking activity. Sera were fractionated to separate immune complexes from gamma-globulins. No free tumor-specific antibody could be detected in fractionated gamma-globulin fractions from 2 patients with osteosarcoma. The sera of these patients had high amounts of immune complexes and high blocking activities.

Antibodies, Neoplasm

A model for human osteosarcoma in hamsters.

An animal model for human osteosarcoma was established in newborn Syrian golden hamsters by injecting productively infected TE-85 cells (cultured human osteosarcoma cells) adjacent to the femur. Tumors were palpable 10 to 15 days following cell injection and enlarged progresively until the animal died (mean survival time was 36 days). The tumor take was 100% and all animals developed pulmonary metastases. Osteoid and bone were identified in sections of the tumor by light and electron microscopy. Invasion of the marrow spaces and adjacent skeletal muscle by the malignant osteoblasts, anaplastic sarcoma cells and multinucleated giant cells was frequently observed. The tumor was transplantable. TE-85 cell surface antigens were demonstrable by immunofluorescence on the surface of the cells of the induced tumors. The present tumor model had unique immunologic characteristics in that no antibodies were demonstrable in the sera of the tumored animals.

Animals

The role of Doppler ultrasound in acute deep vein thrombosis.

Doppler ultrasound in the range of 5 mHz is a simple, portable, inexpensive, and accurate technic for the diagnosis of acute deep vein thrombosis. One hundred sixty patients underwent bilateral Doppler examinations and ascending contrast venography. The overall accuracy was 94 per cent.

Acute Disease