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Biomedical subjects

P B Chretien

Publications and source records attributed to P B Chretien.

At least 19 recordsLinked to original sources

Serum levels of immunoreactive thymosin alpha 1 and thymosin beta 4 in large cohorts of healthy adults.

Enzyme linked immunosorbent assays were used to measure serum levels of immunoreactive thymosin alpha 1 and thymosin beta 4 in 681 healthy adults (range 18 yr-101 yr). Immunoreactive thymosin alpha 1 was found to occur at a geometric mean of 540 pg/ml with a range from 252 to 1158 pg/ml. There were no differences in the levels when analyzed according to race, sex or age. Immunoreactive thymosin beta 4 was measured at a geometric mean of 12.6 ng/ml with a range from 6.9 to 23.0 ng/ml. There were no differences in the levels when analyzed according to race or sex, however, there was a slight upward trend with increasing age. This data may be useful as a reference when monitoring clinical studies, determining the kinetics of drug metabolism and distinguishing patient groups with elevated levels of either of these peptides.

Adolescent

Suppression of cellular immunity by head and neck irradiation. Precipitating factors and reparative mechanisms in an experimental model.

A model was developed in C3H mice to investigate the immunosuppressive effects of head and neck irradiation and to explore mechanisms for repair of the defects. Mice receiving 1200 rad (12 Gy) of head and neck irradiation showed significant depression of delayed-type hypersensitivity, peripheral blood lymphocyte counts, spleen cell counts, and spleen cell production of interleukin-2. Treatment with optimal dosages of thymosin alpha 1 (T alpha-1) produced significant increases in all of these values, in some instances to levels higher than in the nonirradiated controls. In identical experiments with mice irradiated to a portal limited to the pelvic region, T alpha-1 induced only partial remission of the abnormalities. The dose response of T alpha-1 with head and neck irradiation showed a relatively limited dose range for immune restoration, a finding that warrants similar determinations in clinical trials with immunomodulating agents. The results suggest a potential clinical usefulness of T alpha-1 and also interleukin-2 in restoring cellular immunity after irradiation for head and neck cancers. The model appears to be useful for investigating immunomodulating agents before they are clinically evaluated as adjuvants with head and neck irradiation regimens.

Animals

Effects of radiation therapy on T-lymphocyte subpopulations in patients with head and neck cancer.

Cellular immunity was assessed in 85 patients with head and neck cancer with monoclonal antibodies to lymphocyte surface antigens that identify total T cells, helper cells, and suppressor cells. The control group consisted of 22 healthy volunteers. Nine patients who had surgical procedures for benign diseases were also studied. Compared with the controls, the patients with cancer who received radiation therapy had a significant decrease in total lymphocytes, T cells, helper cells, suppressor cells, and decreased helper/suppressor cell ratio. Significant decreases in lymphocyte subpopulations were not detected in patients tested before treatment or in patients treated with surgery alone. The immune deficits observed were prolonged in duration, with some present in the patients studied up to 11 years after radiation therapy. This long-lasting immune depression may have relevance to tumor recurrences and second primaries in patients with head and neck cancer treated by radiation therapy and to attempts at increasing cure rates with adjuvant agents that improve immune reactivity.

Carcinoma, Squamous Cell

Thymosin fraction V and intensive combination chemotherapy. Prolonging the survival of patients with small-cell lung cancer.

Patients with small-cell bronchogenic carcinoma who received intensive remission-induction chemotherapy randomly received either thymosin fraction V, 60 mg/sq m or 20 mg/sq m twice weekly, or no thymosin treatment during the initial six weeks of chemotherapy. Chemotherapy was then continued for two years. Thymosin administration did not increase the complete response rate. Patients receiving thymosin, 60 mg/sq m, had significantly prolonged survival times relative to the other treatment groups. This benefit was due to prolonged relapse-free survival in complete responders to treatment. The mechanism by which thymosin increased survival duration is unclear but may relate to restoration of immune deficits due to disease or treatment.

Antineoplastic Agents

Prognostic value of pre-treatment lymphocyte count and T cell levels in localized bronchogenic carcinoma.

In the patient with clinically localized bronchogenic carcinoma, the pre-treatment peripheral blood lymphocyte count and the thymus-dependent lymphocyte (T cell) level correlated with the prognosis of the tumor histology was either squamous cell, oat cell, or undifferentiated carcinoma. Patients whose pre-treatment lymphocyte count was less than 1,000/ml or whose T cell level was less than 750/ml either died or developed distant metastases by nine months after treatment of their localized tumor. By contrast, 55% of patients whose pre-treatment T cell level was greater than 750/ml were alive and without evidence of metastases nine months after treatment (P less than 0.02). Analysis of survival of these patients by the life-table method through the first post-treatment year further demonstrates the prognostic value of a low pre-treatment lymphocyte count or T cell level. The pre-treatment lymphocyte count and T cell level in patients with adenocarcinoma did not correlate with prognosis.

Adult

Thirty-six-hour preoperative high-dose methotrexate infusion in patients with squamous carcinoma of the head and neck.

Twenty 36-hour infusions of high-dose methotrexate were given preoperatively to 10 patients with head and neck cancer. Plasma methotrexate levels of greater than 1 X 10(-5) M were maintained for 36 hours and declined with primary and secondary plasma half-lives of 1.7 and 9.2 hours following the end of the infusion. Toxicity of this infusion regimen was minimal (10% incidence of significant (WBC less than 2000/mm3) myelosuppression; no renal toxicity) and all patients underwent surgical resection within 3 weeks of therapy without obvious increase in operative complications. Four of ten patients responded to chemotherapy. Further comparison of the therapeutic efficacy of this prolonged preoperative infusion regimen with surgery alone or schedules employing conventional doses or 6-hour infusions of high-dose methotrexate appears warranted.

Aged

Identification and quantitation of B and T cells by cytofluorographic analysis.

With cytofluorographic analysis (CFGA) of cells stained with the fluorescent dye acridine orange (AO), the major peripheral white cell populations--lymphocytes, monocytes, and polymorphonuclear cells--display different characteristics and appear as distinct populations which can be quantitated. In this study we present a method for determining percentages of human T and B cells lymphocyte subpopulations by CFGA and display of the data on a computer-generated 3-dimensional grid. Lymphocytes were depleted of either B, T, or both B and T cells by rosetting with erythrocytes and separated by centrifugation. The B cell and T cell depleted and non-rosetting cell subpopulations localized on constant, distinct areas of the display grid. The percentages of T and B cells in peripheral blood samples from 6 normals analyzed by CFGA did not differ from the results obtained by light microscope counting (LMC).

Adult

Paraplegia due to posttraumatic pelvic arteriovenous fistula treated by surgery and embolization. Case report.

A case is presented in which a posttraumatic pelvic arteriovenous fistula caused progressive paraplegia because of voluminous shunting into the epidural venous system. Surgical ligation and transcatheter embolization of major and minor arterial feeders decreased shunt flow sufficiently to permit direct embolization of the fistula by an injectable plastic. This combined approach may allow obliteration of unresectable acquired or congenital arteriovenous malformations.

Adult

Serum acute-phase proteins and immunoglobulins in patients with gliomas.

Cellular immune competence was found to be impaired in previous studies of patients with malignant brain tumors. In patients with nonneural tumors, we recently found that serum levels of acute-phase proteins were related to immune status as well as to tumor extent. To determine whether the serum proteins in patients with central nervous system tumors show similar changes, levels of acute-phase proteins (alpha1-acid glycoprotein, alpha1-antitrypsin, haptoglobin, C-reactive protein) and immunoglobulins (immunoglobulins G, M, and A) were assayed in patients with gliomas prior to treatment. Compared to normals, significant increases (p less than 0.001) in the acute-phase proteins were found, and the levels were similar to those in patients with nonneural solid neoplasms. Serum immunoglobulins were not significantly increased in patients with gliomas.

Alpha-Globulins

Carcinoma of the lung and cigarette smoking. Effect on serum ribonuclease activity.

Serum ribonuclease levels were determined in 54 patients with lung carcinoma, 74 long-term cigarette smokers, and 172 nonsmokers. The mean serum ribonuclease level was significantly higher in patients with lung carcinoma and long-term smokers compared with healthy nonsmokers (P less than .001). The serum ribonuclease activity level was not related to chronological age, sex, or race of the smoker or nonsmoker population. Forty (75%) of 53 patients with lung cancer and 49 (66%) of 74 smokers had elevated serum ribonuclease levels compared with 13 (7%) of 179 nonsmoker healthy controls (P less than .001). The highest incidence of elevation was noted in patients with epidermoid carcinoma (95%).

Adenocarcinoma

CEA levels in patients with carcinoma of the esophagus.

Serum CEA levels were determined serially by the Hansen Z gel technique on 41 patients with carcinoma of the esophagus and compared to 276 controls. Seventy percent of patients with carcinomas of the esophagus had elevated CEA levels. CEA levels greater than 10.0 ng/ml after therapy correlated with significantly shortened survival. CEA appears promising as an indicator of tumor presence in patients with carcinoma of the esophagus.

Adult