Percutaneous transcatheter infusion and infarction in the treatment of human cancer: Part II.
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Biomedical subjects
Publications and source records attributed to K Wright.
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The effect of the luteolytic hormone prostaglandin F2 alpha (PGF2 alpha) on parameters of LH receptor binding to isolated rat luteal cells was examined. The equilibrium binding constant (0.55 X 10(10) M-1), the association rate constant (0.89 X 10(8) M min-1), and the dissociation rate constant (1.70 X 10(-2) M min-1) were not significantly altered by PGF2 alpha. However, as [125I]iodohCG binding approached equilibrium (less than 2 h) and at equilibrium (greater than 3 h), PGF2 alpha, but not PGE2, consistently reduced LH binding by 10-20%. The LH receptor-binding capacity, determined by Scatchard analysis of [125I]iodo-hCG or [125I]iodo-hLH binding, was reduced from 7.5 +/- 0.1 to 6.4 +/- 0.1 X 10(4) receptors/cell in the presence of PGF2 alpha. This reduction of total cell-bound radioactivity by PGF2 alpha was not due to a change in the rate of hormone internalization and degradation. However, when cells were briefly treated with a pulse of LH (5 ng/ml; 5-10 min), [125I] iodo-hCG (LH) binding increased 20-30% within 2 h, and PGF2 alpha prevented this LH-induced increase. A similar pulse of cAMP analogs did not alter LH binding. We conclude that while the initial binding of LH to its receptor is not altered by PGF2 alpha, it does reduce the final equilibrium level of LH binding by a mechanism that involves a block in the appearance of LH-induced cryptic receptors.
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Depression was studied in a community sample of 962 males and 1555 females aged 55 years and over living in Kentucky in 1981. The sample was representative of the population in Kentucky in that age group and quite similar to that US population. The Center for Epidemiologic Studies Depression Scale was used as a measure of depression, and 13.7% of the males and 18.2% of the females were at or above a previously established cutpoint of 20 for adults over age 55 years. Significant relationships to depression were found in both sexes for age, education, income, housing quality, marital status, and health. For females, the age-depression relationship was not linear. By far the strongest relationship was with self-reported physical health. Significant proportions of those with self-reported kidney or bladder disease, heart trouble, lung trouble, hardening of the arteries, and stroke were above the depression cutpoint. For those conditions, physicians could expect high levels of concomitant depression in about one fourth of males and at least one third of females. These levels of depression were not found for those with high blood pressure, stomach ulcers, cancer, or diabetes. Over half of the sample reported taking prescribed medication and over half had needed a physician's care in the previous six months. Only 3.9% of the males and 3.2% of the females admitted to needing help for mental health problems. Thus, older adults with depression would probably be more likely to seek help from physicians than from services or professionals with explicit mental health labels.
This paper describes a model system for studying the role of helper T cells in the induction of delayed-type hypersensitivity (DTH). Cyclophosphamide- (CP) treated mice sensitized with antigen 3 days later develop high levels of delayed-type immunity; however, DTH cannot be demonstrated in mice that are sensitized with antigen 1 day after drug treatment. The inability to respond to antigen 1 day after CP treatment can be restored if either normal or low-dose primed spleen cells are transferred at the time of sensitization. Although irradiated (1500 rad) normal spleen cells are unable to restore DTH, such treatment has no effect on the primed spleen cell population. The lymphocytes responsible for restoring the DTH response were identified as T cells, in that treatment with anti-Thy-1.2 serum and C abrogated their effect. Furthermore, restoration of the DTH response was dependent on the presence of antigen at the time of lymphocyte transfer; irradiated primed cells could not transfer DTH alone. The DTH effector cells in reconstituted mice were identified as originating from the host and not from the transferred cell population. This was accomplished by using anti-H-2 serum to identify the source of the DTH effector cells after transferring parental (H-2b) irradiated primed spleen cells into CP-treated F1 mice (H-2b,k). Thus, the irradiated transferred cells are behaving as helper T cells and promoting the development of DTH effector cells in the host.
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Segmental and complete hepatic artery embolization with Ivalon (polyvinyl alcohol) particles (0.25 to 1 mm) was performed in 12 dogs to evaluate hepatic function alterations and histopathological changes. In dogs undergoing segmental embolization, liver function alterations were minimal and the liver was normal, both grossly and microscopically, at autopsy. In dogs undergoing complete hepatic embolization, only two had significant elevation of SGOT and alkaline phosphatase levels, which normalized in 2 and 4 weeks; one of these two dogs also had an elevated bilirubin level. A focal hepatic infarct was observed both grossly and microscopically in one dog and only microscopically in four dogs. Two dogs died of pancreatic abscess due to unintentional pancreatic embolization. The study suggested that segmental embolization with Ivalon particles was well tolerated by dogs, and complete hepatic embolization resulted in hepatic function changes and focal infarction comparable with Gelfoam embolization.
Samples of graded, human lung cancer and of normal lung were assayed for total iron, ferritin, and ferritin iron saturation. Both kinds of tissues contained highly variable amounts of total and ferritin iron and had a range of ferritin iron:protein ratios. No quantitative correlations were found between cancer histopathology and these parameters, in contrast to previous findings for transplantable rat hepatomas. Examination of pooled ferritins isolated from normal lung and lung tumors by quantitative polyacrylamide gel electrophoresis, isoelectric focusing before and after acid-urea dissociation, and SDS electrophoresis, revealed no structural differences. It is concluded that at least for the human lung, malignancy of the kind examined causes no change in ferritin gene expression, and that ferritin assays would not be useful in the grading or detection of human lung cancer.
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A simple, nonsurgical means of differentiating biliary atresia (BA) from neonatal hepatitis has remained elusive. To determine its diagnostic usefulness, serum gamma-glutamyl transpeptidase (GGTP) levels were measured prospectively in 17 infants (aged 5 to 16 weeks) admitted consecutively to rule out BA. Seven patients were found to have BA, seven had neonatal hepatitis (NH), and three had alpha 1-antitrypsin (A1A) deficiency. The mean maximal GGTP level in those patients with NH (183 +/- 54 IU/L) was significantly lower than that found in patients with BA (760 +/- 492 IU/L) or A1A deficiency (1,725 +/- 921 IU/L). In the 14 patients without A1A deficiency, a serum GGTP level greater than 300 IU/L correctly identified six of seven patients with BA, while a GGTP level less than 300 IU/L correctly identified seven of seven patients with NH, although including one false-negative finding, in a patient with choledochal cyst and BA.
The feasibility and efficiency of ventilation by high-frequency oscillation (HFO) were examined in animals with diffuse hemorrhagic lung disease. Twenty-four hours after injection with 0.12 ml/kg oleic acid, 11 spontaneously breathing rabbits had a mean (+/- SD) arterial O2 partial pressure (PaO2) of 65 +/- 16 Torr and arterial CO2 partial pressure (PaCO2) of 38 +/- 7 Torr [inspired fractional O2 concentration (FIO2) of 0.21]. Following paralysis animals were ventilated using a high-frequency oscillator for periods of 20 min followed by three successive hyperinflations to prevent atelectasis. Maintaining a constant mean airway pressure (MAP) of 6 cmH2O and fresh gas flow (FGF) of 2 1/min (FIO2 = 0.21), all combinations of frequency (5, 10, 20, and 30 Hz) and stroke volume (Vs) 2.6, 5.0, and 8.9 ml) were tested. At each frequency, an increase in Vs tended to lower mean PaCO2. At each Vs, CO2 elimination appeared maximal at 20 Hz, an effect attributable to decreasing effective Vs with increasing frequency. With constant Vs, MAP, and frequency, increasing FGF from 1 to 2 or 61/min decreased mean PaCO2 (P less than 0.05). With constant Vs, frequency, and FGF, increases in MAP from 2 to 10 cmH2O increased mean PaO2 (P less than 0.05). HFO, coupled with periodic hyperinflation, supports satisfactory gas exchange in rabbits with oleic acid lung injury. The efficiency of gas exchange is improved by independent increases in Vs, FGF, MAP, or frequency.
Edema formation was studied using in situ rabbit lungs perfused with normal 5.0 g/dl) and low (0.1 g/dl) albumin solutions. Measurements were made of the ratio of wet weight to dry weight of the lungs corrected for the residual vascular volume, [(W/D)ev] and the ratio of extravascular 22Na+ to extravascular water volume. Edema formation in the 5 g/dl lungs was insignificant during a 60-min perfusion interval. A moderate amount of edema was found in 0.1 g/dl lungs: (W/D)ev = 5.30 +/- 0.12 (SE) compared with 4.66 +/- 0.11 in the 5 g/dl lungs. Much greater rates of edema formation were found in the 0.1 g/dl lungs when left atrial pressures were increased from 0 to 10 Torr; (W/D)ev reached 7.89 +/- 0.50 in 60 min compared with 5.66 +/- 0.23 in the 5 g/dl lungs. No additional edema formation occurred when albumin concentrations were decreased from 0.1 g/dl to below 0.01 g/dl. Albumin concentration gradients across the capillary wall appear to increase with elevations in capillary pressure.
The real-time high resolution mechanical sonographic sector scanner is a convenient and useful instrument for the detection of intracranial hemorrhage in premature infants. Experience with 27 infants with intracranial hemorrhage detected by sonography and confirmed by computed tomography (CT) or by autopsy is analyzed. The severity of the hemorrhage shown by those methods was graded by an accepted classification for standardized reporting. The extent of intraparenchymal and intraventricular hemorrhage was accurately assessed by sonography in all cases except for small amounts of blood in normal sized ventricles in five of 12 instances. Sonography also failed to detect subarachnoid hemorrhage in each of 13 cases. There were no known false-positive sonograms. From this experience the authors believe sonographic sector scanning should be the initial examination in all infants at high risk for intracranial hemorrhage. When the ventricles are of normal size, CT scanning is recommended to search for small intraventricular hemorrhage that may not be detected by sonography. For subarachnoid bleeding, CT is preferable to sonography.
Ceruloplasmin was assayed as enzyme activity, as antigen, and as total copper in serum samples from 150 male lung cancer patients and comparable numbers of male controls. By all three assays, ceruloplasmin was significantly increased above the normal before treatment, and the degree of elevation was related to TNM stage [i.e., the International Union Against Cancer classification system based on extent of primary tumor (T), condition of lymph nodes (N), and absence of presence of metastases (M)]. Surgery had no immediate effects, but in patients who evidence of disease for longer periods, ceruloplasmin returned to nearly normal values. High levels of ceruloplasmin was elevated in 6 of 9 patients before tumor recurrence; 2 of 3 smokers (in the first panel of sera) with elevated ceruloplasmin levels subsequently developed lung cancer. The relative merits of the three assays were compared. Some sex- and age-related differences among normal controls were apparent. The results of pilot studies on men with gastrointestinal cancer and women with breast cancer are presented. It is concluded that only in limited situations will assays of ceruloplasmin aid in diagnosis, prognosis, and long-term monitoring of cancer patients.
Post-transfusion purpura (PTP) is a recently separated category of thrombocytopenic purpura occurring mainly in women. It is an acute, severe thrombocytopenic state with clinical manifestations of hemorrhage that may be fatal. It usually occurs 5 to 8 days after transfusion, usually after administration of whole blood. The typical patient is a middle-aged, multiparous white woman who has received a transfusion and has undergone an operation, often a gynecologic procedure. Diagnosis may be suspected by normal clotting studies, bone marrow biopsy showing increased megakaryocytes, and demonstration of a potent antibody reactive against platelets by clot-retraction inhibition, complement fixation, or 51Cr-release studies. The treatment of choice is exchange transfusion or plasmapheresis, unless these procedures are medically contraindicated. Because of the lack of reports in the gynecology literature on PTP, a case report and discussion are presented.
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These studies describe the conditions under which antibody-forming cells and TDTH cells are selectively induced in vitro. TDTH cells are preferentially stimulated when high doses of antigen are included in the culture. Antibody-forming cells, on the other hand, are optimally stimulated with a 100 to 1000-fold less concentration of antigen. The conditions that optimally stimulate TDTH cells also induce a population of suppressor T cells that inhibit the antibody response. However, although their inductive requirements are similar, the suppressor T cells of antibody formation are a distinct subpopulation of cells from the TDTH cells. Whereas the suppressor T cells are LY-1-, 2+, 4-, 6+, and Ia+; the TDTH cells are Ly-1+, 2+/-, 4-, 6+, and Ia-. Furthermore, the DTH cells are sensitive to high doses of irradiation, whereas the suppressor cells are resistant. Based on the Ly phenotype and the kinetics of suppression, the suppressor T cells are not the "feedback suppressors" that have been identified in other systems. The system described in this paper provides a means whereby the cells that regulate humoral and CMI can be studied in vitro.
This study was undertaken to compare quantitative changes observed in serial determinations of T-cell rosette values during the first 21-28 postoperative days in two groups of cadaver-kidney allograft patients. The antithymocyte (ATG)-treated group received ATG (UpJohn) immunosuppression in addition to a standard regimen of immunosuppressive treatment. the second group did not receive ATG but were also on the same standard immunosuppressive regiment. Absolute number of T-cell rosettes per cubic millimeter and per cent baseline rosettes were determined in each case rather than per cent rosette-forming cells. The results indicate that ATG-treated patients have the most dramatic drop in the levels of peripheral blood T-cell rosettes. Also, 60 per cent of the patients in the untreated group experienced cell-mediated immune (CMI) rejection episodes compared to 17 per cent in the ATG-treated group. This suggests that the high levels of T-cell rosettes in the peripheral blood of kidney allograft recipients may be associated with CMI rejection episodes. These findings indicate that monitoring E-rosette levels in the peripheral blood of allograft patients can provide pertinent information that may lead to accurate predictions of CMI rejection episodes.