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Biomedical subjects

J M Daly

Publications and source records attributed to J M Daly.

At least 145 records · Page 8Linked to original sources
PubMed1990

Flow cytometry and prognostic implications in patients with solid tumors.

Flow cytometric DNA content analysis is a rapid, quantitative method of determining the DNA ploidy status and proliferative index of a given tumor. Abnormal DNA content, or aneuploidy, has been recognized as a marker of malignancy and is present in about 70 per cent of solid tumors. In the majority of solid tumors, the consensus is that the presence of an aneuploid tumor predicts a poorer over-all survival rate and a shorter disease-free interval, indicating that patients with diploid tumors have a more favorable prognosis than those with aneuploid tumors. The prognostic implications of an abnormal DNA content, therefore, suggest either a higher risk of relapse, a worsening of survival rate or a risk for progression of disease in stages I and II carcinoma of the breast, carcinoma of the colon and rectum, superficial carcinoma of the bladder and malignant melanoma. Thus, the assessment of cellular DNA content should be regarded as an additional prognostic determinant and should play an ancillary role in the decisions regarding the management of patients with malignant disease. With the introduction of more sophisticated technology, it will be possible to simultaneously assay for DNA ploidy and cell cycle distribution in addition to a series of tumor markers, such as CEA, and various products of oncogenes, thus providing further understanding of the heterogeneity of solid tumor cells.

Biomarkers, Tumor↗
PubMed1990

Effects of verapamil and degradable starch microspheres during hepatic artery infusion of doxorubicin.

Chemotherapeutic tumoricidal activity may be enhanced by altering regional blood flow between host organ and tumor by transient embolization with degradable starch microspheres (DSMs) or by altering cellular drug transport with drugs such as verapamil. This study evaluated the effects of intraarterial verapamil and DSMs on hemodynamics and doxorubicin tissue levels. Rabbits (n = 34) with hepatic VX-2 carcinomas underwent hepatic artery infusion of doxurubicin (3 mg/kg) alone, with two doses of verapamil, and with verapamil plus DSMs. Blood pressure and heart rate were monitored, and heart, liver, and tumor tissue was obtained after 30 or 90 minutes. After verapamil (2 mg/kg) alone, mean heart rate decreased but infusion of verapamil plus DSMs resulted in only a 14% decrease in mean heart rate. Thirty minutes after drug infusions, mean hepatic tissue levels of doxorubicin were increased significantly by 2 mg/kg of verapamil compared with results with 1 mg/kg of verapamil and those in control groups (p less than 0.05). Mean tumor doxorubicin levels were not significantly different with verapamil alone. Verapamil plus DSMs or DSMs alone resulted in significantly lower mean hepatic and myocardial levels and increased mean tumor/liver ratios of doxorubicin after 90 minutes, compared with results in control or verapamil-alone groups. These results suggest that hepatic tumor drug levels are more affected by changes in regional blood flow with DSMs than by cellular drug transport changes caused by calcium channel blockers such as verapamil.

Animals↗
PubMed1989

The influence of natural killer cells in neuroblastoma.

Human neuroblastoma (NRB) cell lines are markedly sensitive to natural killer (NK) cell lysis in vitro, but patients with NRBs have low or absent NK activity. This study evaluated the NK sensitivity of murine NRBs (C1300 and TBJ) in the regulation of NRB growth and determined the effects of recombinant (r) interferon gamma and recombinant interleukin 2 (rIL-2). Both basal (8% +/- 3% specific cytotoxicity) and induced (20% +/- 3%) NK lyses of C1300-NRB were observed. In vivo depletion of NK cells with anti-asialo GM-1 significantly enhanced growth of C1300-NRB and decreased survival. Treatment with r-interferon gamma or rIL-2 on days 1 through 3 after C1300-NRB inoculation significantly prolonged the mean tumor latency period, decreased the tumor growth rate, and enhanced in vitro NK killing of C1300-NRB and YAC-1. The effects of r-interferon gamma and IL-2 were abrogated by pretreatment with anti-asialo GM-1. These results demonstrated that NK cells form one important component of regulation of a murine NRB, but immunomodulation with potent lymphokines requires cooperation of more than one cell type.

Animals↗
PubMed1989

Infusional versus systemic chemotherapy for liver metastases from colorectal cancer.

It is clear from these studies that intrahepatic arterial infusion of floxuridine produces significantly higher response rates than does systemic infusion of the same drugs. Nevertheless, survival is the most important consideration when comparing two methods of treatment, and at present, there is only a slightly improved survival rate in those patients who receive intrahepatic infusional therapy. However, palliation of the patient and the effect on the quality of life should be taken into account, and these high response rates suggest an effective palliative measure to be offered to patients with this advanced disease. It is hoped that in the future the development of methods to identify those patients who will respond to this form of therapy, together with new ways to increase drug uptake by the tumors, will translate the better response rates achieved into better survival rates.

Adult↗
PubMed1989

Magnetic resonance imaging and magnetic resonance spectroscopy of bone tumors and bone marrow disease.

The authors have made use of an integrated magnetic resonance imaging/spectroscopy (MRI/MRS) examination to study seven patients with a variety of bone tumors. The spatial localization method used in the 31P portion of the examination was surface coil localization and a one-dimensional chemical shift imaging method (3 cases). The authors found that the precision of spatial localization was critical in many of these cases, since most of these bone tumors were surrounded by muscle tissue that contained high concentrations of phosphocreatine (PCr). For this reason, they suggest that the metabolite ratios should be referenced to the adenosine triphosphate (beta-NTP) resonance rather than PCr. The phosphate monoester (PME) to beta-NTP ratio was elevated as compared with normal muscle in all of the bone tumors studied. The authors found that all of these tumors exhibited pHs between 7.0 and 7.2, which are similar to the values found for normal muscle. They also show the feasibility of using a line-selective proton chemical shift imaging sequence with high spatial resolution for investigating changes in the fatty composition of bone marrow. This method is illustrated in an example of a patient with advanced avascular necrosis in the femoral heads.

Adolescent↗
PubMed1989

Regional hepatic arterial infusion of degradable starch microspheres increases fluorodeoxyuridine (FUdR) tumor uptake.

Hepatic metastases of colorectal carcinoma demonstrate a dose response to chemotherapy. In animal studies hepatic arterial infusion of chemotherapeutic agents with degradable starch microspheres (DSMs) produces a redistribution of blood flow between tumor and liver and an increase in tumor drug levels. In this prospective clinical study in patients with colorectal metastases, we evaluated the effect of DSMs on liver and tumor levels of fluoropyrimidines after intraoperative administration through the hepatic artery. Fourteen patients underwent infusion of radiolabeled fluorodeoxyuridine, 14C-FUdR (0.15 mg/kg, 0.5 microCi/kg), followed 2 to 5 minutes later by infusion of 3H-FUdR (0.15 mg/kg, 1.0 microCi/kg) without (n = 3) or with (n = 11) DMS. Seven of the later patients underwent major hepatic resection and tissue mapping of drug distribution, and four patients underwent biopsy procedures to remove specimens of liver and tumor 5 minutes after microsphere infusion. Administration of DSMs with FUdR increased tumor drug levels as measured by 3H-FUdR (5.9 +/- 4.4 vs 17.1 +/- 9.4 nmol/gm, p = 0.07) without altering hepatic drug levels (35.7 +/- 10.9 vs 30.2 +/- 20.9 nmol/gm, p = NS) and significantly increased the tumor/liver drug ratio of tritiated fluoropyrimidines (0.16 +/- 0.09 to 0.63 +/- 0.13, p = 0.03). Fluoropyrimidine levels in tumor and liver correlated with blood flow as measured by technetium-99m macroaggregated albumin retention. Thus, hepatic arterial administration of DSMs in human beings enhances tumor FUdR levels and may be useful in increasing tumor cytotoxicity and decreasing systemic toxicity during regional hepatic infusion.

Aged↗
PubMed1988

Increased adriamycin levels in hepatic implants of rabbit Vx-2 carcinoma from regional infusion.

Regional infusion chemotherapy for the treatment of primary or secondary hepatic cancer should allow delivery of a higher drug concentration to the tumor with decreased systemic exposure when compared with systemic therapy. Fifteen rabbits, each implanted with two hepatic Vx-2 tumors, were treated with infusion of Adriamycin (3 mg/kg and 7.5 muCi of [14C]Adriamycin) through the hepatic artery (n = 5), portal vein (n = 5), and a systemic vein (n = 5) at 20 mg/min. 99Tc-labeled macroaggregated albumin flow images documented specific hepatic perfusion in selected rabbits using this technique. Thirty min after infusion the animals were sacrificed, and multiple specimens of liver, tumor, and heart were taken for liquid scintillation counting and high-performance liquid chromatography. The 14C label remained associated with Adriamycin and metabolites. After systemic infusion 11.5 nmol/g of Adriamycin were found in tumor, and 32.4 nmol/g were found in liver. Infusion of Adriamycin through the hepatic artery produced drug levels of 34.3 nmol/g of tumor and 48.4 nmol/g of liver, while infusion through the portal vein produced drug levels of 6.5 nmol/g of tumor and 54.4 nmol/g of liver. The drug concentration in tumor was significantly higher after hepatic artery infusion compared with systemic (P less than 0.05) or portal vein (P less than 0.01) infusion. The tumor/liver ratio of [14C]Adriamycin tissue levels after hepatic artery infusion was greater than that measured after systemic vein treatment (no overlap of the 90% confidence intervals). Systemic infusion of Adriamycin produced a higher level of Adriamycin in the heart (13.6 nmol/g) than did hepatic artery (10.9 nmol/g) or portal vein (8.9 nmol/g) infusion. Hepatic artery infusion achieved the highest tumor Adriamycin level compared with systemic vein and portal vein infusion. The results suggest that these tumor implants are supplied primarily by the hepatic artery, that clearance of Adriamycin is efficient after regional infusion, and that systemic toxicity may be reduced using intraarterial infusion of Adriamycin for hepatic tumors.

Animals↗
PubMed1988

Ornithine decarboxylase levels in the rectal mucosa of patients with colonic neoplasia.

Ornithine decarboxylase (ODC) activity in biopsy specimens of normal-appearing rectal mucosa was measured in 15 control patients, 5 patients with colon adenomas, and 11 patients with colon cancer. While women had significantly higher ODC activity than men, ODC activity was increased regardless of gender in the rectal mucosal biopsies of patients with benign or malignant colonic neoplasia compared with those of controls. The positive predictive value of ODC activity for remote colonic neoplasia was 61% for women and 91% for men. The results provide a rationale for long-term studies of ODC activity in rectal mucosa as a biological marker of high risk for large bowel neoplasia.

Adenoma↗
PubMed1988

Resection of the liver for colorectal carcinoma metastases. A multi-institutional study of long-term survivors.

In this review of a collected series of patients undergoing hepatic resection for colorectal metastases, 100 patients were found to have survived greater than five years from the time of resection. Of these 100 long-term survivors, 71 remain disease-free through the last follow-up, 19 recurred prior to five years, and ten recurred after five years. Patient characteristics that may have contributed to survival were examined. Procedures performed included five trisegmentectomies, 32 lobectomies, 16 left lateral segmentectomies, and 45 wedge resections. The margin of resection was recorded in 27 patients, one of whom had a positive margin, nine of whom had a less than or equal to 1-cm margin, and 17 of whom had a greater than 1-cm margin. Eighty-one patients had a solitary metastasis to the liver, 11 patients had two metastases, one patient had three metastases, and four patients had four metastases. Thirty patients had Stage C primary carcinoma, 40 had Stage B primary carcinoma, and one had Stage A primary carcinoma. The disease-free interval from the time of colon resection to the time of liver resection was less than one year in 65 patients, and greater than one year in 34 patients. Three patients had bilobar metastases. Four of the patients had extrahepatic disease resected simultaneously with the liver resection. Though several contraindications to hepatic resection have been proposed in the past, five-year survival has been found in patients with extrahepatic disease resected simultaneously, patients with bilobar metastases, patients with multiple metastases, and patients with positive margins. Five-year disease-free survivors are also present in each of these subsets. It is concluded that five-year survival is possible in the presence of reported contraindications to resection, and therefore that the decision to resect the liver must be individualized.

Adult↗
PubMed1988

The use of quantitative perfusion fluorometry to measure relative tumor and liver blood flow after transient microembolization.

Optimal chemotherapy delivery to the tumor depends on regional drug concentration, tumor perfusion, tissue drug uptake, and metabolism. Modulation of tumor blood flow has been used to improve tumor response to treatment. Transient microembolization is one method to alter regional blood flow, but its effects on relative changes in tumor and liver blood flow have not been previously measured. This study used quantitative perfusion fluorometry (QPF) to evaluate blood flow distribution in liver and tumor before and after hepatic arterial infusion of degradable starch microspheres (DSMs) in 10 New Zealand white rabbits. QPF was compared with radioactive xenon-133 washout, an established method for measuring blood flow. Xenon-133 was injected intraparenchymally and the clearance rate was measured allowing calculation of relative blood flow. QPF was then used to measure liver and tumor blood flow in a hepatic VX-2 tumor model after hepatic artery injection of DSMs. Initial tumor blood flow was 55% of liver flow. DSMs produced a significant and transient decrease in hepatic blood flow that was decreased to 40% of baseline after 25 min. Changes in relative hepatic blood flow after DSMs as measured by QPF correlated strongly with results obtained by xenon-133 washout (R = 0.97, P less than 0.01). Fluorometry's simplicity and reliability may be clinically useful to evaluate tumor blood flow characteristics.

Animals↗
PubMed1988

Arginine, protein malnutrition, and cancer.

The amino acid arginine has anabolic and immunostimulatory properties. This study evaluated the potency of arginine in limiting the severe nutritional and immunological insults of protein calorie malnutrition and increasing tumor load. In protein-depleted A/J mice (n = 340) bearing either an immunogenic (C1300) or poorly immunogenic (TBJ) neuroblastoma, arginine supplementation [1%] significantly augmented T lymphocyte responses (mitogenesis, interleukin-2 production) compared with both a glycine-supplemented and nonsupplemented group. Arginine supplementation significantly retarded the growth of C1300 and prolonged median host survival. These results correlated with augmented autologous mixed lymphocyte tumor cell responses and enhanced specific cytotoxicity. This anti-tumor effect was not demonstrated in mice bearing TBJ where both arginine and glycine stimulated tumor growth compared with nonsupplemented mice. There was no significant difference between arginine and glycine in preservation of carcass weight. These studies suggest that the immunostimulatory effects of arginine are not due to supplemental nitrogen and that an associated antitumor effect is dependent on tumor antigenicity.

Animals↗
PubMed1988

Resting energy expenditure in lung and colon cancer.

Elevated resting energy expenditure (REE) is a possible mechanism of cancer cachexia. We measured REE by whole-body direct calorimetry in patients with colon and non-small cell lung cancer and compared the results with REE in groups of healthy subjects and in patients with anorexia nervosa, with nonmalignant gastrointestinal (GI) disease, with miscellaneous reasons for weight loss, and with chronic lung disease. The mean REE of the cancer patients was not different from healthy subjects, those with GI disease, miscellaneous causes of cachexia, and chronic lung disease, and there was no significant difference in REE between those cancer patients with weight loss and controls with weight loss, except for the anorexia nervosa patients. The REE of the anorexia nervosa patients (female) was significantly lower than the REE of females with lung cancer. Weight loss correlated with REE in female lung cancer patients. Serial comparison of REE of ten cancer patients who lost 5% to 18% of their body weight during study showed no consistent change in REE. We conclude that patients with colon and non-small cell lung cancer, including those with weight loss, have REE similar to normal controls. Relative hypermetabolism may contribute to cancer cachexia, as may absolute hypermetabolism in some subsets of cancer patients.

Anorexia Nervosa↗
PubMed1988

Benign mesenchymoma of the palate: report of a case.

A case of benign mesenchymoma of the hard palate is presented. The lesion was completely excised and the tumor margins were shown to be free of disease. Within 4 months a second noncontiguous lesion arose of the opposite side of the palate and was also removed. Whether this represented a distinctly new lesion or possibly one which was seeded through previous diagnostic efforts was difficult to ascertain. Follow-up for more than 2 years has not revealed any further evidence of neoplasia.

Female↗
PubMed1988

Immune and metabolic effects of arginine in the surgical patient.

Arginine enhances immune function and promotes nitrogen retention in animal models, but its immunomodulatory effects in surgical patients are unknown. This randomized, prospective trial evaluated the immune and metabolic effects of supplemental L-arginine (25 g/day, n = 16) or isonitrogenous L-glycine (43 g/day, n = 14) in 30 cancer patients undergoing major operation. Two groups of patients received either arginine or glycine for 7 days after surgery as a supplement to a graduated enteral diet. Nitrogen balance was measured daily, and immune parameters were determined both before and after surgery, on Days 1, 4, and 7. The T-lymphocyte response to concanavalin A (con A) and PHA and dual marker phenotype analysis of lymphocyte (CD2, CD4, CD4/DR, CD8, CD8/DR) and macrophage (M3/DR) subsets were determined. Mean age, degree of preoperative weight loss, disease stage, number of perioperative transfusions, and calorie and nitrogen intake were similar for the groups studied. Mean daily nitrogen balance (-2.3 g/day in the arginine group vs. -3.9 g/day in the glycine group) was not significantly different between the two groups, but positive mean nitrogen balance was achieved only in the arginine group between Days 5 and 7 after surgery. Supplemental arginine significantly enhanced the mean T-lymphocyte response (stimulation index) to con A from 45 +/- 26 on postoperative Day 1 to 72 +/- 47 and 87 +/- 49 on postoperative Days 4 and 7, compared with the values of 29 +/- 15, 27 +/- 20, and 33 +/- 34 in the glycine group at the same time points, respectively. Supplemental arginine increased mean CD4 phenotype (% T-cells) on postoperative Days 1 and 7 from 25 +/- 9 to 43 +/- 14, compared with the values of 30 +/- 14 and 29 +/- 13 in the glycine group (p less than 0.05). The beneficial effect of arginine on the immune system appeared distinct from its more moderate effect on nitrogen metabolism. As a nutrient substrate, arginine was nontoxic, and may benefit surgical patients who are at increased risk of infection.

Aged↗
PubMed1988

Brain shrinkage in alcoholics is not caused by changes in hydration: a pathological study.

Measurement of the water content of the cerebral white matter in 26 control and 24 alcoholic cases supports in vivo MRI studies and previous necropsy studies which appeared to show an increase in the water content in the alcoholic group. This negates the hypothesis that reversible brain shrinkage in alcoholics is caused by changes in the state of hydration.

Aged↗
PubMed1988

Immunomodulatory mechanisms of arginine.

Dietary supplementation with the amino acid arginine augments T-lymphocyte activation in response to mitogens in clinical and experimental studies. In experimental models arginine enhances specific T cell antitumor immunity. The mechanism of these immunostimulatory effects of arginine on T cell function is unclear, and the scope and specificity of arginine's influence on other components of the effector immune response such as natural killer (NK) cells and macrophages are unknown. To evaluate the role of arginine in these responses, CBA/J mice (n = 100) were randomized to receive either 1% arginine supplementation or isonitrogenous (1.7%) glycine supplementation for at least 10 days. There was no significant differences in mean body weight between groups during feeding. Arginine supplementation significantly (p less than 0.05) enhanced cytotoxic T-lymphocyte development, poly IC-inducible NK activity, and the kinetics of interleukin-2 receptor expression on activated T cells. Basal- and endotoxin-induced macrophage interleukin-1 and superoxide production were not significantly influenced by supplemental arginine although macrophage cytotoxicity in response to gamma-interferon was augmented (p = 0.07). In subsequent in vitro studies we established that certain effects (NK, cytotoxic T-lymphocyte, and T cell activation) were reproducible after preincubation for 72 hours in pharmacologic levels of arginine. The data strongly suggest that arginine mediates a direct effect on components of the immune system, which results in enhanced production or use of lymphokines.

Animals↗