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Biomedical subjects

C F Contant

Publications and source records attributed to C F Contant.

63 records · Page 4Linked to original sources

Enteral hyperalimentation in head injury.

The objectives of this study were to determine the ability of enteral hyperalimentation to meet the caloric and protein requirements in acute severe head injury, and to study the effect of increasing protein intake on nitrogen balance. This consecutive series of 20 patients suffered acute severe head injury and remained comatose for at least 24 hours. They were all without other major injuries, and were treated with steroids. These patients were randomly placed in two comparable treatment groups: one group was fed with an enteral formula containing 14% of its calories as protein and the other group received a formula containing 22% protein calories. Feedings were advanced to replace 140% of caloric expenditure measured by indirect calorimetry, averaging 3500 kcal/24 hr. Balance periods of the targeted intake were 7 days in duration, and were begun during the 1st week after injury for 65% of patients and in the 2nd week after injury for 35% of patients. The lower protein group received an average of 26.8 gm/24 hr of nitrogen, equivalent to 188 gm of protein, and the higher protein group 34.3 gm/24 hr, equivalent to 231 gm of protein. Nitrogen balance was -9.2 +/- 6.7 gm/24 hr in the lower protein group and -5.3 +/- 5.0 gm/24 hr in the higher protein group, but the difference did not reach statistical significance because of sample size and variability in extent of catabolism among patients. Despite the hyperalimentation, there was a mean negative cumulative nitrogen balance of 200 gm by the 2nd week after injury, and only three patients achieved net nitrogen equilibrium for the 7-day balance period. Despite enteral hyperalimentation, the patients' weight fell by 15% in the 2nd week, serum albumin was often decreased, and creatinine-height index decreased over time but remained in a normal range. Monitoring urinary urea nitrogen, which has been advocated as a generally available technique for measuring urinary nitrogen concentration, was found to be a poor measure of urinary nitrogen excretion. This work has demonstrated: 1) that high caloric and protein feedings may be delivered for prolonged periods enterally for most patients in the acute phase of head injury with few metabolic complications, and 2) that increasing the nitrogen content of feedings from 14% to 22% may somewhat improve nitrogen retention, although nitrogen equilibrium is seldom achieved.

Adult↗

Diet diversity and nutrient intake.

Variety is espoused as a key to dietary adequacy, yet data from new shortcut dietary measures suggest that intakes of relatively few foods can accurately classify individuals according to nutrient intake. This study examines diet diversity, caloric intake, and nutrient density values as contributors to the level of selected nutrients in the diets of 1,747 white men and 1,898 white women, 18 to 34 years old, completing the 24-hour recall in NHANES II. Nutrient intake was directly related to both number of foods eaten and total calories consumed, as well as to nutrient density values. For fat, saturated fat, and potassium, higher caloric consumption alone may account for substantial differences in nutrient intakes between the lowest and highest quartiles. For cholesterol, calcium, and vitamin A, differences in dietary density were more important in explaining nutrient intake differences. Both caloric intake and nutrient density influence sodium intake from food sources. For some nutrients, an overall measure of diversity may be useful for estimating intakes. For others, nutrient-specific diversity indexes would likely be needed. Knowledge of specific foods in diets with high levels of nutrients could aid the construction of food frequency instruments.

Adolescent↗

Change in red blood cell relaxation with hydration: application to MR imaging of hemorrhage.

T1 and T2 were measured in unclotted blood samples with 0.24- and 4.7-T spectrometers. The fraction by weight of intracellular water in the red blood cells (RBCs) was varied by either osmotic manipulation or density separation in concentrated (packed RBCs) and dilute (RBCs suspended in buffer or serum) samples. Reducing the cell water content caused a moderate decrease in T1 and a profound decrease in T2 at both 0.24 and 4.7 T. Conversely, increasing the cell water content caused an increase in both T1 and T2. The authors conclude that dehydrated RBCs in an area of hemorrhage would cause a substantial decrease in signal intensity on long TR/TE (T2-weighted) images. Overhydration of RBCs would have the opposite effect.

Adult↗

Adenovirus-mediated combination suicide and cytokine gene therapy for bladder cancer.

BACKGROUND: The present study tests the hypothesis that adenovirus-mediated transfer of murine IL-2 (ADV/RSV-mIL-2) alone or in combination with HSV-tk + GCV will improve antitumorigenic response in the murine MBT-2 model. MATERIALS AND METHODS: mIL-2 production and toxicity were determined in vitro using an ELISA and a cell proliferation assay. Tumor-bearing animals were randomly assigned into four treatment groups and directly injected with combinations of ADV/RSV-tk and ADV/RSV-mIL-2. In a separate experiment, the above-mentioned groups were followed by two subsequent treatments with ADV/RSV-mIL-2. RESULTS: Transduced MBT-2 cells were able to express mIL-2 in a time and dose dependent fashion. We could not demonstrate any improvement in antitumorigenic response with mIL-2 gene therapy alone or in combination with HSV-tk-suicide gene therapy over HSV-tk suicide gene therapy alone. CONCLUSIONS: Although ADV/RSV-mIL-2 transduced MBT-2 cells were able to produce large amounts of mIL-2 in vitro, we could not demonstrate significant tumor growth inhibition by adding mIL-2 gene therapy to suicide gene therapy. The growth inhibitory effects of sequential suicide and cytokine gene therapy were transient and not superior to single dose suicide and cytokine gene therapy.

Adenoviridae↗

Adenovirus-mediated suicide gene therapy for bladder cancer: comparison of the cytomegalovirus- and Rous sarcoma virus-promoter.

BACKGROUND: To compare efficacy and toxicity of the human cytomegalovirus-immediate-early (CMV) promoter and the Rous-sarcoma-virus (RSV) promoter to express thymidine kinase (tk) for adenovirus-mediated suicide gene therapy of experimental bladder cancer in vivo and in vitro. MATERIALS AND METHODS: In vitro: 3 human (5637, RT-4 and TCC-SUP) and one murine (MBT-2) bladder cancer cell line were exposed to ADV/RSV-tk or ADV/CMV-tk vectors and cell survival was determined. In vivo: Subcutaneous tumors were established and adenovirus vectors were injected 10 days later. RESULTS: In vitro: ADV/CMV-tk was up to 4 times more potent in terms of cell killing than ADV/RSV-tk. In vivo: ADV/CMV-tk had a three-fold higher antitumor potency per viral particle as compared to ADV/RSV-tk. Higher doses of ADV/CMV-tk caused treatment-associated hepatotoxicity. CONCLUSIONS: Our results confirm the efficacy of adenovirus-mediated tk suicide gene therapy in the treatment of experimental bladder cancer. Dose-related toxicity was greater with the use of ADV/CMV-tk, but lower doses achieved the same efficacy as ADV/RSV-tk.

Adenoviruses, Human↗

Human epithelial ovarian cancer xenotransplants into nude mice can be cured by adenovirus-mediated thymidine kinase gene therapy.

BACKGROUND: Adenovirus-mediated suicide gene therapy of ovarian cancer has effective anti-tumor effects in vitro and in vivo. By transduction of ovarian adenocarcinoma with the Herpes Simplex Thymidine Kinase gene and subsequent treatment with the antiviral agent ganciclovir, prolongation of survival has been described in nude mice. So far, however, in animal models of solid tumors no cures have been reported after gene therapy. METHODS: In a prospective randomized experimental design 76 mice with xenotransplanted serous ovarian carcinoma were treated with three different doses of ADV/RSV-TK at three different time points followed by intraperitoneal ganciclovir administration. The experiment was designed to show significance of survival differences upon doubling of the number of survived days at a p-value of 0.05 with a power of 80%. The endpoint of the trial was survival. RESULTS: Treatment response was seen in all treated animals evident by significant prolongation of survival. Treatment response was dependent on the therapeutic viral dose and the tumor burden of the animal at the time of treatment. Two out of eight mice with early disease have now survived ten months without evidence of disease with untreated animals dying after nineteen days. Subcutaneous tumor development at the injection site was the reason of death in the remaining six mice of this group. CONCLUSIONS: Intraperitoneal ADV/RSV-TK suicide gene therapy of epithelial ovarian cancer in combination with ganciclovir administration can cure nude mice with early disease. This treatment modality may lend itself to incorporation into the current treatment concept of human ovarian malignancy. Clinical trials are warranted.

Adenoviridae↗

The efficacy of adenovirus-mediated gene therapy of ovarian cancer is enhanced by using the cytomegalovirus promoter.

The cytomegalovirus(CMV) promoter is considered one of the strongest positive regulators. In this study toxicity, cell killing efficacy and bystander effect of Rous Sarcoma Virus(RSV) driven herpes simplex thymidine kinase(TK) gene therapy was compared with CMV driven TK gene therapy in three ovarian cancer cell lines with different growth patterns using a 3-(4,5-dimethylthiazol)-2,5-diphenyl tetra-zolium bromide (MTT) based assay. ADV/CMV-TK was shown to be 2 to 10 times more effective in tumor cell killing than ADV/RSV-TK. The difference in cell killing efficacy between ADV/CMV-TK and ADV/RSV-TK was dependent on the individual cell line. A CMV promoter dependent eight to ten fold improvement in cell killing efficacy was observed in the relatively slow growing SKOV3 cell line which is not easily transducible, while only a 2 to 4 fold difference was observed in the easily transducible OV-CA-2774 and OV-CA-1225 cell lines. ADV/CMV-TK also showed a stronger bystander effect than ADV/RSV-TK in all three ovarian cancer cell lines. Our data demonstrated that the efficacy of adenovirus-mediated gene therapy of ovarian cancer can be enhanced by using the CMV promoter without increasing toxicity.

Adenoviridae↗