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Biomedical subjects

C L Miller

Publications and source records attributed to C L Miller.

At least 109 records · Page 6Linked to original sources

The immunomodulating effect of TP5 and indomethacin in burn-induced hypoimmunity.

Hypoimmunity after major trauma and thermal injury appears to predispose to septicemia. An increase of immune suppressive T cells and the inhibitory monocytes product PGE2 has been demonstrated postburn and are suggested as contributing to postburn hypoimmunity. TP5, the biologically active part of thymopoientin, has an immunomodulating effect on T cells. Indomethacin, an irreversible blocker of the prostaglandin synthesis has been suggested to reduce the inhibitory monocytes-mediated immunosuppression. In this study strains 2 and 13 guinea pigs received 20-30% TBSA scald burn and were subsequently injected with either TP5 or indomethacin or a combination of both on the 3 following days postburn. The ability of splenocytes to produce a secondary immune response to SRBC was measured in the in vitro AFC assay. The animals who had received TP5 and indomethacin showed significant improvement in their ability to mount an immune response in the AFC assay.

Animals↗

A novel method of assessing completeness of tumor registration.

A random sampling method of measuring the completeness of registration of cancer patients was tested at a university referral hospital. The target population consisted of all inpatients and nonprivate outpatients with in situ or invasive malignancies. The medical records of a random sample of all hospital records active in the last five years were reviewed to determine their reportability and inclusion in the tumor registry (Method A). Traditional casefinding assessment methods were also employed by conducting a complete review of four commonly used hospital sources for a short time period (Method B). The primary purpose of the study was methodologic; namely, to test the feasibility of Method A and to characterize it relative to the more traditional Method B. The estimated missed case rates using Methods A and B (3% and 5%, respectively) are not directly comparable because not all outpatient information is recorded in the medical record. It is concluded that as a means of completeness assessment, Method A can be feasible, cost effective, and useful in other institutions provided certain conditions are met: (1) an appropriate random sample of the target population can be obtained; (2) all relevant information is available in a unit medical record; (3) the reviewer is fully aware of the reportability criteria.

Data Collection↗

Effects of gold compounds on the function of phagocytic cells. II. Inhibition of superoxide radical generation by tripeptide-activated polymorphonuclear leukocytes.

The effect of sodium aurothiomalate and triethylphosphine gold on the generation of superoxide radicals by chemotactic tripeptide-activated polymorphonuclear leukocytes has been investigated using a cytochrome C reduction technique. Neither gold compound inhibited the binding of the tripeptide to cells. Sodium aurothiomalate in concentrations ranging from 1 to 100 micrograms/ml produced mild, nonsignificant inhibition of the generation of superoxide radicals. In contrast, triethylphosphine gold at a concentration of 0.25 microgram/ml was associated with a mild enhancement of superoxide radical production, but the enhancement was not statistically significant. At concentrations of 1.25 micrograms/ml and above, there was a profound inhibition of superoxide radical production by these activated cells. Since the products of the respiratory burst, including superoxide, are thought to be inflammatory mediators, it is postulated that the inhibition of superoxide radical generation by gold compounds may be another mechanism by which the compounds modulate their antiinflammatory effects in patients with rheumatoid disease.

Binding Sites↗

Energy expenditure in malnourished cancer patients.

It is widely believed that the presence of a malignancy causes increased energy expenditure in the cancer patient. To test this hypothesis, resting energy expenditure (REE) was measured by bedside indirect calorimetry in 200 heterogeneous hospitalized cancer patients. Measured resting energy expenditure (REE-M) was compared with expected energy expenditure (REE-P) as defined by the Harris-Benedict formula. The study population consisted of 77 males and 123 females with a variety of tumor types: 44% with gastrointestinal malignancy, 29% with gynecologic malignancy, and 19% with a malignancy of genitourinary origin. Patients were classified as hypometabolic (REE less than 90% of predicted), normometabolic (90-110% of predicted) or hypermetabolic (greater than 110% of predicted). Fifty-nine per cent of patients exhibited aberrant energy expenditure outside the normal range. Thirty-three per cent were hypometabolic (79.2% REE-P), 41% were normometabolic (99.5% REE-P), and 26% were hypermetabolic (121.9% REE-P) (p less than 0.001). Aberrations in REE were not due to age, height, weight, sex, nutritional status (% weight loss, visceral protein status), tumor burden (no gross tumor, local, or disseminated disease), or presence of liver metastasis. Hypermetabolic patients had significantly longer duration of disease (p less than 0.04) than normometabolic patients (32.8 vs. 12.8 months), indicating that the duration of a malignancy may have a major impact upon energy metabolism. Cancer patients exhibit major aberrations in energy metabolism, but are not uniformly hypermetabolic. Energy expenditure cannot be accurately predicted in cancer patients using standard predictive formulae.

Aged↗

Adrenalectomy in the guinea pig: operative and perioperative management.

Guinea pigs were anesthetized by epidural injection of xylocaine 20 minutes following the administration of chlorpromazine, cortisone, and hydrocortisone. The right adrenal gland was removed aseptically by careful blunt dissection. Ten milliliters of warm saline containing tobramycin was given subcutaneously at the conclusion of the surgery, and the guinea pig was returned to a recovery cage containing a heating pad. Ten days later, the left adrenal gland was removed using similar procedures.

Adrenalectomy↗

Results of radiation therapy given after radical hysterectomy.

Two hundred twelve patients with carcinoma of the cervix, Stage I (193 patients) and Stage II (19 patients), were treated by radical hysterectomy at the Hospital of the University of Pennsylvania during the period from 1955-1977. Pathology reports were evaluated for the presence of the following factors thought to indicate an unfavorable prognosis: (1) positive pelvic lymph nodes (31 patients); (2) parametrial extension (22 patients); and (3) infiltration of the margin of resection (14 patients). Fifty-one high risk patients (HR) with one or more of these pathologic findings have five and ten year survivals of 55% and 30%, respectively. This compares with five- and ten-year survivals of 87% and 85%, respectively, for patients without these findings. Local recurrences were noted in 20/50 (40%) HR patients versus 23/159 (13.2%) non-HR patients (P less than .001). A retrospective analysis revealed that 21 of 50 evaluable HR patients received adjunctive postoperative pelvic irradiation (HR-XRT). Although the reduction in local recurrence in the treated group approached statistical significance, 5/21 versus 15/29 (0.1 greater than P greater than 0.05), the five- and ten-year survival did not differ significantly. Twenty-four patients initially treated with surgery received definitive radiation therapy for local recurrence. The five- and ten-year survivals for the time of recurrence were 22% and 15%. Our findings suggest that postoperative irradiation may be beneficial in controlling local disease in a subgroup of radical hysterectomy patients who are at high risk for recurrence. Since the ultimate incidence of extra pelvic metastasis for the high risk and the recurrent group is 32% and 67%, respectively, however, it appears that improved survival awaits the development of effective systemic adjuvant therapy.

Adenocarcinoma↗

Prognosis of pulmonary scar carcinoma.

Eighty-one patients with resectable primary peripheral lung carcinomas were studied to determine the effect of associated scarring on prognosis. Twelve tumors (15%) originated from bronchi. 24 (30%) were associated with scars, and 45 (55%) were not associated with either bronchus or scar (non-scar). Scar carcinomas differed significantly in cell type from bronchogenic and non-scar tumors in that 21 (88%) scar carcinomas were either adenocarcinomas or bronchioloalveolar carcinomas (p less than 0.001). Origin (bronchogenic, scar, non-scar) independent of cell type and tumor stage did not significantly influence survival. Stage of disease independent of cell type or origin affected survival (p less than 0.0001), as did cell type independent of tumor stage or origin (p less than 0.0001). Stage I disease and bronchioloalveolar carcinoma were associated with longer survival, while Stage II or III disease, small cell anaplastic carcinoma, and adenocarcinoma were associated with reduced survival. We conclude that associated scar influences cell type of peripheral lung carcinoma but does not influence patient survival, even among patients with similar cell type and stage of disease.

Adenocarcinoma, Bronchiolo-Alveolar↗

Generation of tissue factor by patient monocytes: correlation to thromboembolic complications.

Thromboembolic complications are often a common pathological consequence of severe soft tissue trauma. Recent demonstration that monocytes (M0) produce tissue factor (TF) has led to the suggestion that these TF producing M0 might play a role in coagulopathy. We have previously demonstrated that trauma patients with splenectomy develop aberrant monocyte function and this patient group is also known to be at high risk of hypercoagulability episodes. This paper is an initial report on the use of M0 TF as an indicator of and/or correlated to clotting episodes. Monocytes isolated form the Ficoll-Hypaque purified mononuclear cells of 46 normal individuals, 17 trauma patients and 6 surgical controls were assayed at 3 day post-injury intervals for their levels of TF activity. Changes in monocyte TF activity were correlated to increases in the fractional catabolic rate (FCR) of 125 I-fibrinogen. Trauma patients were retrospectively divided into those whose FcR was elevated to a level indicative of coagulopathy and those whose FCR levels were not associated with coagulation abnormalities. All trauma patients who exhibited significantly increased FCR experienced thromboembolic episodes and had monocytes whose TF activity was increased an average of 300% (mean = 47 units vs mean = 12 units) over surgical controls. These increase in monocyte TF activity occurred at 6-13 days post injury and preceded clinical manifestation of coagulopathy by 4-6 days. The increased monocyte TF activity demonstrated in this study was significantly correlated to detection of pathologically increased FCR (R = 0.850) and compared to other indices of hypercoagulability.

Blood Coagulation↗

Chromosome-mediated gene transfer results in two classes of unstable transformants.

The human thymidine kinase gene has been transferred from HeLa S3 cells to mouse LM(TK-) cells via isolated metaphase chromosomes. Efficient transfer of the thymidine kinase gene (1.8 X 10(-5) colonies per recipient cell) was obtained when the donor chromosomes were precipitated with calcium phosphate and the recipient cells were treated with 10% (vol/vol) dimethyl sulfoxide. Thirty-five independent cell lines were analyzed in detail. Cytologically detectable donor chromosome fragments were observed in 14% of the cell lines. Many of the transformed cell lines were also found to express the human genes for galactokinase (23% of the transformed cell lines) and procollagen type I (69% of the transformed cell lines), which are syntenic to thymidine kinase on human chromosome 17. On the basis of stability analyses, three classes of transformed cell lines were defined and characterized. One class of transformants was stable, showing no loss of the transferred phenotype in the absence of selection. A second group of transformants was unstable, losing the thymidine kinase phenotype at a rate of 1.5-2.5% per day. This group of transformants was found to possess large donor chromosome fragments (macrotransgenomes) and relatively low levels of donor gene activity. The third group of transformants lost the thymidine kinase phenotype rapidly, at a rate of 6-10% per day. These cell lines contained small, cytologically undetectable transgenomes (microtransgenomes) and overexpressed the transferred thymidine kinase gene.

Animals↗

Effect of nutrition on nonspecific inflammatory and specific immune host defense systems.

A truly prophylactic regimen for reducing the incidence of nosocomial infections would attempt to prevent the development of acquired deficiencies in host defenses. Monocyte function is a pivotal link between the specific immune system and non-specific inflammatory responses. We have found that decreased monocyte production of plasminogen activator correlates with a decrease in specific immune function and complement interaction. Simultaneously, monocyte generation of tissue procoagulant factor increases. Use of nutritional support of antibiotics in a judicious fashion may prevent those trauma-mediated or disease-mediated alterations in monocyte function which correlate with development of nosocomial infections.

Animals↗