Reproducibility of a self-administered diet history questionnaire administered three times over three different seasons.

The reproducibility of the widely used Health Habits and History Questionnaire (HHHQ) for estimating "usual past-year" nutrient intake was examined. The HHHQ was self-administered on three occasions during three different seasons; 68 women (avg age 43 yrs) provided usable data for all three questionnaires in the appropriate seasons. Intraclass correlations (ICC) among the three administrations ranged from 0.56 (carotene) to 0.82 (fat as percentage of energy), with a median of 0.72. Thus, reliability was moderate to good, and season of administration/ordinality generally had little impact on ranking of individuals. The point estimates of intake of energy and a number of nutrients were higher in the first administration (winter). Except for dietary fiber and possibly carotene, most differences disappeared when adjusted for energy using a nutrient density approach, as well as using repeated-measures regression models. The higher intake in the first administration may be due more to either learning or fatigue effect rather than an effect of seasonal food availability on perceptions of "usual" intake. These data should be used in conjunction with validity data in the future to help evaluate the gain in precision of group means (and changes in these means) and improved estimates of odds ratios and correlations between nutrients and factors such as serum values, if a questionnaire is administered more than once.

Modulation of cell cycle kinetics in human cancer with total parenteral nutrition.

Prior DNA flow cytometric data from the laboratory of the Division of Surgical Oncology, Massey Cancer Center, demonstrated an increase in the hyperdiploid compartment of tumor cells taken from patients with squamous cell carcinoma of the head and neck after a course of total parenteral nutrition (TPN). To assess a putative increase in the percentage of tumor cells actively synthesizing DNA in this system, the authors administered bromodeoxyuridine (BrdU) intravenously to ten patients before and after the administration of TPN. Cell suspensions prepared from biopsy specimens of normal oral mucosa and tumor tissue were analyzed with flow cytometric study. Before TPN administration, the mean percentage of tumor cells incorporating BrdU was 2.47 +/- 1.11%. After TPN administration, the percentage of S-phase cells increased significantly (P less than 0.05) to a mean of 4.52 +/- 2.67%. Before TPN was given, normal mucosa demonstrated a mean of 7.97 +/- 2.69% of cells incorporating BrdU. After TPN was given, a mean of 8.47 +/- 2.51% was seen (not significant [NS]). A potential strategy for the use of TPN to enhance tumor cell susceptibility to S-phase-specific chemotherapy is strongly suggested by these data.

Noninterference of isosulfan blue on estrogen-receptor activity.

Because a 1% sterile solution of methylene blue used for occult breast tumor localization has been shown to interfere with the estrogen-receptor protein (ERP) binding-capacity assay, isosulfan blue in a 1% injection was studied as a potential alternate stain. Cytosols derived from ERP-positive lyophilized powders and human breast tissue were evaluated with and without varying levels of treatment with isosulfan blue. No modification of the ERP-specific binding capacity was found with this stain. The use of isosulfan blue for localization of occult breast tumor is suggested when an ERP binding capacity assay is anticipated.

Effect of methylene blue on estrogen-receptor activity.

Methylene blue in a 1% sterile solution for injection to help localize occult breast tumor was shown to interfere with the estrogen-receptor protein (ERP) binding-capacity assay. Cytosols derived from ERP-positive lyophilized powders and human breast tissue were evaluated with and without varying levels of treatment with methylene blue. Cytosols treated with 0.1% methylene blue, a clinically significant level, demonstrated a substantially lower ERP binding capacity compared with control cytosols. This alteration was found to be due to a reduction in specific binding capacity and not to an alteration in apparent cytosol protein concentration. The use of methylene blue for occult breast tumor localization is not recommended when an ERP binding-capacity assay is anticipated.

Effects of parenteral nutrition on cell cycle kinetics of head and neck cancer.

We attempted to determine whether nutritional supplementation with total parenteral nutrition (TPN) of malnourished patients with untreated squamous cell carcinoma of the head and neck alters tumor growth. Fourteen patients underwent biopsies of normal and malignant tissues and were then placed in either a control or adjuvant TPN group. Nutritional parameters and biopsies were repeated over the ensuing three to 17 days. Biopsy specimens were analyzed by flow cytometry for changes in the percentage of hyperdiploid cells (PHC) and aneuploidy. The PHC of tumor biopsy specimens in patients given TPN increased significantly from 15.1 +/- 2.0 to 27.3 +/- 3.3, while no such change occurred in normal mucosa. The PHC after TPN was significantly greater in the patients with cancer than that observed in the controls. These data demonstrate that TPN may have a stimulatory effect on tumor cell cycle kinetics in humans.

The efficacy of total parenteral nutrition in malnourished tumor-bearing rats.

The current study was designed to compare the efficacy of total parenteral nutrition (TPN), provided either before or after tumor removal, in replenishing protein stores in the malnourished tumor-bearing (TB) host. Fisher 344 rats bearing a transplantable methylcholanthrene (MCA)-induced sarcoma were used. After the animals were cachectic from their tumor, a central venous catheter was inserted. At the time of catheter insertion, the animals were randomized into two groups. Group I rats had the TB hindlimb amputated whereas Group II rats had the nontumor bearing (NTB) hindlimb amputated. After amputation, all animals were given TPN for 10 days then sacrificed. The results demonstrated that TB rats (Group II) had a significantly decreased tumor-free carcass weight in contrast to nontumor bearing rats (Group I). Furthermore, the TB animals had a significantly increased body weight gain after completion of TPN. This difference in body weight proved to be due almost entirely to the weight of the growing tumor. Compositional analysis revealed a significantly decreased protein stores and significantly increased fat stores of both the carcass and liver of the TB animals compared to those which the tumor had been resected. The results of the data suggest that TPN given to the sarcoma-bearing animal after tumor removal is better utilized for replenishing protein stores than when it is provided before removal of the tumor.

Effects of three feeding schedules on tumor and host of Lewis lung carcinoma-bearing mice.

The effect of three feeding schedules on tumor and host were examined in Lewis Lung bearing (TB) and nontumor bearing (NTB) C57/B1 mice. Both NTB and TB animals were divided into three groups: the control groups which were fed ad libitum; the intermittent fed (IMF) groups were fed for 32 hr and fasted for 16 hr in each 48-hr cycle, and the alternate day fed (ADF) groups were fed for a 24-hr interval in each 48-hr cycle. The animals were killed at the end of the fifteenth day, following a fed day for all groups. In the NTB groups, only the ADF group showed decreased food intake and lower body weight gain as compared to their control group. In the TB mice, as compared to their control group, the IMF group showed a significant reduction in the mean tumor weight with no change in the mean host weight, even though the daily food intakes of these two groups were the same over the experimental interval. In contrast, the ADF group showed reductions in both host and tumor weights as compared to their control group. The tumor to host weight ratios were significantly reduced for both the IMF and ADF groups as compared to the ratios found for the control groups, which suggests a differential effect on the tumor and on the host due to the feeding schedule. As assessed by the protein, RNA, and DNA concentrations, no compositional differences were noted for the tumors obtained from the animals that were maintained on each of the three different feeding schedules. In the NTB mice, no differences in tissue leucine (Leu) oxidation occurred between the groups for liver and skeletal muscle, whereas in the TB animals in vitro Leu oxidation capability by skeletal muscle specimens was markedly enhanced in the ADF group, but no difference was noted for the IMF group of the TB mice when compared to the control group. Taken together, these results suggest that the 32-hr fed:16-hr fast schedule (IMF) was beneficial and the 24-hr fed:24-hr fast schedule was detrimental compared to the ad libitum feeding schedule with respect to tumor and host relationships.

Estrogen receptors in primary breast cancer.

Estrogen receptor (ER) activity was assayed in 132 patients undergoing mastectomy for primary breast cancer and in 75 patients whose initial treatment for metastatic cancer was endocrine manipulation. Estrogen receptor status correlated with response to endocrine therapy. Among patients whose ER activity was assayed in the primary tumor, ER-positive patients had an improved disease-free survival (independent of stage or nodal or menopausal status) after mastectomy when compared with ER-negative patients (P less than .05). The ER-positive and ER-negative patients receiving adjuvant chemotherapy had similar disease-free survivals. These data confirm that patients with ER-positive primary tumors have a better prognosis than patients with ER-negative primary tumors. Although adjuvant chemotherapy improves the prognosis in patients with histologically positive lymph nodes in both ER-positive and ER-negative patients, the disease-free survivals in ER-negative patients may improve to a greater extent than in ER-positive patients.

Effect of hydrazine exposure on hepatic triacylglycerol biosynthesis.

Acute hydrazine exposure elevated rat liver triacylglycerol content and produced a rapid rise in triacylglycerol production from sn-[1,3-14C]glycerol 3-phosphate by liver homogenate and microsomal fractions. Hydrazine treatment also increased the incorporation of [1,3-14C]glycerol into hepatic triacylglycerol by the intact animal. Homogenates of hepatocyte monolayers exposed to hydrazine in vitro also exhibited an increased capacity to form triacylglycerol from sn-[1,3-14C]glycerol 3-phosphate. Hydrazine-dependent increases in hepatic triacylglycerol production measured in vitro correlated well with an increase in microsomal phosphatidate phosphohydrolase (EC 3.1.3.4) activity. Therefore, the fatty liver associated with hydrazine exposure may be explained in part by a rise in the enzymatic capacity of hepatic triacylglycerol biosynthesis.

Urinary glucose and vitamin C.

The recent popularization of self-prescribed large doses of vitamin C has increased the possibility for erroneous conclusions to be drawn from standard clinical methods used in urinary glucose monitoring, due to interference with these methods by the greatly elevated excretion of vitamin C. The coupled-enzyme-chromogen strip tests showed erroneously negative glucose levels in urines of both a diabetic individual and a subject with a genetic low renal threshold for glucose when they were supplementing their normal diets with 1-2 g vitamin C per day. With this regimen, their urinary vitamin C levels reached 200 mg/dl (11.4 mmol/l). For normal urine with vitamin C added, false-positive tests for glucose were found using Benedict's reagent when vitamin C was present at 250 mg/dl (14.3 mmol/l) or higher concentrations. In diabetic individuals consuming large quantities of vitamin C, this interference with standard coupled-enzyme-chromogen strip tests or Benedict's test could present a significant problem in diagnosis and clinical management of the disease. A simple anion exchange method of treating the urine was used to correct the false results.