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J Vaage

Publications and source records attributed to J Vaage.

At least 145 records · Page 8Linked to original sources
PubMed1985

Methylprednisolone reduces vascular resistance in hypoxic and atelectatic lungs.

The effect of pharmacological doses of methylprednisolone (MP) on the pulmonary vasoconstrictor response to hypoxia has been investigated in two groups of isolated rat lung preparations, one consisting of ventilated, and the other of atelectatic lungs. In both groups, MP reduced the vasoconstrictor response to hypoxia in a dose-dependent fashion. At a perfusate concentration of 3 mmol/l of MP, the response was reduced by about 80%. On the contrary, the vasoconstrictor response to injections of standardized doses of angiotensin II, used as an independent vasoconstrictor substance, were not significantly changed by MP, even when administered at a concentration which completely abolished the response to hypoxia. We suggest that MP inhibits the pulmonary vasoconstrictor response to hypoxia without influencing the general reactivity of the pulmonary vascular bed.

Animals↗
PubMed1985

High-dose corticosteroids in thoracic trauma.

Experimental data show that lung injury may be prevented or reduced when steroids are administered early. It seems, however, difficult to reverse a lung injury which is already established. Accordingly, we have since 1976 administered high doses of methylprednisolone already on admission in patients with multiple rib fractures and/or flail chest (30 mg/kg i.v. X 3 at 8 hr intervals). A retrospective analysis of 143 patients with severe blunt chest trauma, most of whom were multitraumatized (72%) and many in shock (19%) revealed a significantly lower mortality for 44 steroid treated patients compared to 99 nonsteroid patients with similar injuries (9.1 vs 29.3%, p = 0.02). The incidence of bronchial infection and septicemia was not increased in steroid treated patients. There was also a lower incidence of multiple organ failure in the steroid treated group (4.5%) as compared to the control group (9.1%, n.s.). Hemodynamic and blood gas changes were examined in a prospective controlled study including 40 patients with multiple rib fractures and lung contusion. Pulmonary vascular resistance (PVR), which is a good parameter of injury severity, was reduced significantly in the steroid treated group. This led to a reduction in right heart work. The corticosteroid induced reduction in PVR was seen whether the patient was on a ventilator or breathed spontaneously. There were no significant differences in the a-v oxygen difference or in intrapulmonary shunting. Both the number of complications and the duration of artificial respiration were reduced in the steroid group.

Female↗
PubMed1985

Effects of high-dose corticosteroids on the pulmonary circulation.

A major controversy in the treatment of the Adult Respiratory Distress Syndrome (ARDS) is the role of steroids, which may attenuate permeability as well as pulmonary vascular resistance (PVR). Empirically methylprednisolone (MP) in high doses (30 mg/kg) has been "the steroid of choice" in clinical practice. By autoradiography MP has been shown to penetrate more easily into lung tissue than other steroids tested. MP prevented the late phase increase in lung vascular permeability to endotoxin in sheep, whereas the inhibition of the pulmonary hypertensive response was far less pronounced. In human septic ARDS MP reduced both PVR and the increased vascular permeability. However, a few patients characterized by more severe ARDS did not respond to MP. There is some evidence that steroids may modulate both pre- and postcapillary vasomotion in the lungs. MP was found to inhibit pulmonary venoconstriction as well as pulmonary erythrocyte sludging in canine hemorrhagic shock. Oleic acid induced edema also appears to be attenuated by MP. This effect is partly due to a lowering of hydrostatic pressure in the lung capillaries, because MP blocks the downstream resistance increase. Hypoxic pulmonary vasoconstriction has predominantly a precapillary localisation. MP inhibits hypoxic vasoconstriction in a dose-dependent fashion in isolated rat lungs, but does not cause a general dampening of vascular reactivity, as the pulmonary constrictor response to angiotensin II is unchanged. However, MP inhibits histamine-induced vasoconstriction in isolated canine lung lobes. The increased vascular resistance in atelectatic lungs is also inhibited by MP. Corticosteroids may alter the reaction of the pulmonary vasculature to various stimuli or agents by influencing the release of mediators, for instance, the cyclooxygenase and lipoxygenase products of arachidonic acid, modulate the action of mediators, reducing the activation of leukocytes and/or platelets, or changing the state of the pulmonary vascular muscle cells. Which mechanisms are active in the various situations are at present objects of pure speculation. However, in most situations with ARDS a reduction in pulmonary arterial pressure and PVR may be regarded as beneficial.

Airway Resistance↗
PubMed1985

Morphological observations during developing concomitant immunity against a C3H/He mammary tumor.

During the developing phase of concomitant immunity against primary s.c. implants of the mammary carcinoma MC2, responder cells identified as Lyt 1 and Lyt 2 T-cell subsets and B-cells showed little tendency to infiltrate among the cells of the implants and did not appear to have any direct cytotoxic effect. Macrophages were also not cytotoxic at this time, but they were closely associated with the formation of a fibrous cellular capsule, always found around tumors in arrested growth or in regression. After a period of growth, about 20% of the MC2 implants regressed spontaneously. Surgical disruption of the capsules formed around 5-week-old primary tumor implants did lead to more frequent regressions, showing that a capsule that could destroy a tumor slowly also shielded the tumor against highly activated and effective systemic rejection mechanisms. In mice less than fully immunized with 3-week-old primary implants, the accumulation of responder cells at a second implant was rapid, and the development of a capsule was accelerated. Only the macrophages had developed a tendency to infiltrate among the tumor cells. Implants in partially immune mice had a lower mitotic index than did implants in normal mice. Of the second implants, 30% did not reach palpable size, and 42% regressed after a period of growth. Only after at least 5 weeks of immunization did a rapid destruction of second implants become evident. The tumor-destructive process was associated with infiltration by activated macrophages and was completed in 3 to 6 days.

Animals↗
PubMed1984

Corticosteroids in the treatment of blunt injury of the chest.

In a prospective, controlled study, the effects of large doses of methylprednisolone sodium succinate (MP) were examined in patients subjected to severe blunt injury of the chest. Forty patients with multiple fractures of ribs were selected for the study. The majority of the patients had associated extrathoracic injuries. Chest X-ray films revealed changes characteristic of pulmonary contusion in all cases. Twenty patients were given MP 30 mg/kg body weight intravenously and were compared with 20 patients receiving no steroids, but who were otherwise treated identically. There were no differences between the two groups with respect to the A-VO2 difference and intrapulmonary shunting. However, the steroid treatment led to a significant reduction in pulmonary vascular resistance and to a reduction of the work of the right side of the heart. The number of complications and periods of artificial respiration were reduced in the steroid group. All patients survived.

Adult↗
PubMed1984

Occurrence of shared nonviral tumor-associated transplantation-type antigens among C3H/He mammary carcinomas.

The occurrence of shared nonviral tumor-associated antigens among 18 immunogenic C3H/He mammary carcinomas was investigated in vivo. By cross-immunization and s.c. challenge between pairs of tumors in 37 different combinations, six of the tumors were found to cross-immunize with one to three other tumors. A minimum of three different antigenic specificities were found to be shared among cross-reacting tumors.

Animals↗
PubMed1984

Relationship between tumor growth characteristics and preferential sites of growth.

The anterior-posterior incidence of spontaneous mammary tumor development and the anterior-posterior gradient of growth potential among transplanted tumors was studied in C3H/He and C3Hf/He mice. The relative incidence of spontaneous tumor development in the five mammary gland pairs showed no anterior-posterior bias, but it was in proportion to the quantity of tissue in the individual mammary glands. The transplantability and growth rate of 164 spontaneous C3H/He and 67 spontaneous C3Hf/He mammary carcinomas were tested and compared in anterior and posterior subcutaneous sites and at mammary implantation sites. Initially, in their early transplant generations, most subcutaneous tumor implants (67%) grew significantly better near the shoulder than in an implantation site near the hip. At the same time, implants from the same tumor tissue grew equally well in anterior (#2) and posterior (#4) mammary glands. Without exception, all transplanted tumors grew better in a mammary gland than at a subcutaneous site. Some tumors (12%) that initially would grow only in mammary glands gained subcutaneous transplantability with increased growth rate. With increasing growth rate, the tumors' anterior subcutaneous growth preference decreased. Anterior subcutaneous growth preference was not related to immunologic tumor characteristics. Implants of slow-growing tumors grew better in the anterior subcutaneous implantation site where the greater blood flow improved their growth conditions and survival rate.

Animals↗
PubMed1983

Effects on metastases of drug therapy during developing and established tumor immunity.

The effectiveness of treatment with cyclophosphamide, methotrexate and 5-fluorouracil was studied during the s.c. and pulmonary growth of syngeneic C3H/He mammary carcinomas. Treatments with cyclophosphamide, methotrexate and 5-fluorouracil during the primary induction of immunity against a mouse mammary carcinoma inhibited the growth of the tumor, but also inhibited the development of an effective immune resistance against subsequent implants of the same tumor. However, drug treatments of mice with established tumor immunity gave added benefit without detectable depression of immune resistance.

Animals↗
PubMed1983

Host resistance to metastasis from mouse mammary carcinomas.

Although undisturbed primary mouse mammary tumors may give rise to overt metastases, these have generally been observed near the terminal stage of progressive tumor growth. Unlike malignant breast disease in women, metastases are seldom the cause of death in mice, and in some strains as few as 2% of mammary tumor hosts may be affected (1). Highly metastatic tumors may, of course, be found, and hosts of the mammary carcinoma WHT all develop metastases (2). Evidence from animal models suggests that host defense reactions against immunogenic tumors may affect the incidence of metastatic spread (3-5). But nonimmunogenic and weakly immunogenic tumors probably represent the majority of mammary carcinomas (2, 6, 7), and this class was once considered outside control by the host. However, natural protective factors are also known which may prevent metastasis independently of specific antitumor immunity (8-10). There are therefore most likely several different biological factors and mechanisms which prevent circulating, viable cancer cells from developing into metastases. But one can not yet generalize whether natural resistance factors or induced resistance factors are the most important, or whether any resistance factors are as important in preventing metastases as is the basic unacceptability of cells in heterotopic locations. This review will not attempt to present a comprehensive analysis of cell-mediated and humoral immunity to mouse mammary tumors because this topic has recently been exhaustively treated in the reviews by Stutman (11) and Blair (12). We will focus primarily on information from in vivo investigations of the role of host resistance in the control of mammary tumor cells progressing through successive levels of metastasis from the primary tumor, through lymphatic or hematogenous dissemination, to colonization of distant organs.

Animals↗
PubMed1983

Determination of components of the plasma proteolytic enzyme systems gives information of prognostic value in patients with multiple trauma.

Components of the plasma proteolytic enzyme systems were studied in 15 multiple trauma patients. There were 9 survivors and 6 fatal cases. All fatal cases had sepsis and/or post traumatic adult respiratory distress syndrome. Within the first day after trauma significantly reduced values were found for plasma prekallikrein (PKK), Hageman factor (HF) and Antithrombin III (AT III). In the survivors these parameters were normalized within the first five days after the injury. In the fatal cases, however, the same parameters remained reduced or declined during the observation period. The fatal cases also revealed a high frequency of positive ethanol gelation tests (EGT), elevated serum fibrin - fibrinogen degradation products (FDP) values and persisting low platelet counts. Analyses of plasma samples from both survivors and fatal cases, fractions by Sephadex G-150 gel filtration, demonstrated alpha 2-macroglobulin - plasma kallikrein complexes. These findings demonstrate activation of the kallikrein-kinin system as a part of pathological plasma proteolysis in multiple trauma patients. Persistent reductions of PKK, HF and AT III combined with positive EGT, elevated FDP values and reduced platelet counts indicate a poor prognosis.

Antithrombin III↗
PubMed1983

Plasma cell infiltrate of the primary tumor as a source of early systemic protection against metastases in mice.

Histologic examination of sc implants of the syngeneic C3H/He mammary carcinoma MC2 showed that the accumulation of a large number of lymphoid cells in the stroma around the implants in C3H/He mice was a constant feature of the early primary host response. This stromal reaction had two main components, the first composed of small lymphocytes and the second composed of larger blast cells with a high proportion of plasma cells. The surgical removal of a 6-day-old tumor implant with its surrounding stromal reaction, if performed 4 days before systemic dissemination of MC2 cells via injection into the left ventricle, resulted in a more frequent growth of the disseminated cells as compared to the frequency of growth in mice carrying their tumor implants. This increased frequency of growth in surgically cured mice could be reduced by repeated transfusions of plasma from MC2-bearing hosts. Repeated ip injections of antigen, in the form of 2 X 10(5) inactivated tumor cells after tumor excision, did not support the development of strong systemic resistance against metastases. When sublethal whole-body radiation was given before the sc tumor implant, the stromal reaction was much reduced, and the surgical removal of sc tumor implants from irradiated mice resulted in only a minor increase in the growth of tumor cells injected into the circulation compared to the growth of tumor cells injected into irradiated mice carrying their tumor implants. It appears that a strong, local primary immune reaction may act as a temporary accessory lymphoid organ, constituting an early and potent source of systemic immune protective factors.

Animals↗
PubMed1983

Mammary tumor growth inhibition in C3H/He mice by long-term Bacillus Calmette-Guérin immunoprophylaxis versus enhancement by primary Bacillus Calmette-Guérin therapy.

The effects of long-term prophylactic use of and the effects of treatments with Bacillus Calmette-Guérin (BCG) and methanol extraction residue of BCG have been compared in C3H/He mice implanted with the immunogenic syngeneic mammary carcinoma MC2. The effect of long-term BCG treatment on the development of spontaneous mammary tumors was also investigated. Enhanced resistance to primary tumor development and MC2 growth was only seen in groups of mice that had received long-term pretreatments with BCG or methanol extraction residue of BCG. A negative effect of BCG treatment on host resistance was seen in animals that were given their first injection of BCG and received their first MC2 implant at the same time. Previous immunization against BCG or against MC2 prevented detectable impairment of host resistance by BCG treatment. These observations suggest that the initial phase of BCG infection may have a negative effect on the development of an immune response against cancer. Prolonged, multidose prophylactic administration of BCG may be required to achieve enhanced protection.

Adjuvants, Immunologic↗
PubMed1983

Long-term cyclophosphamide treatments against primary mammary tumors in C3H/He mice.

Tumor-free inbred female C3H/He mice were given weekly injections of cyclophosphamide to prevent or delay the expected occurrence of spontaneous mammary carcinomas. Chemotherapy was started at an age when the mice would already have developed preneoplastic hyperplastic alveolar nodules and tumors were likely to appear within a few weeks. Treatments were given for periods ranging from 10 to 50 weeks with various schedules and doses. The mice were observed for the development of tumors until they died or were killed. Tumors were excised as they appeared. Treatments were most effective in reduction of the number of primary tumors when started early and given continuously. Longer term, low-dose treatments gave better results than short-term, high-dose treatments, although the total dose given was the same. The prophylactic effect of the drug appeared to be by the destruction of occult, drug-sensitive tumors, rather than by delay of their appearance. The toxicity of moderate, continuous drug administration was well tolerated with no mortality and only minor transient weight loss.

Animals↗
PubMed1982

Chromogenic peptide substrate assays in patients with multiple trauma.

Daily monitoring of the plasma proteolytic enzyme systems i.e. the coagulation, the fibrinolytic and the kallikrein-kinin system in multitraumatized patients with chromogenic substrate assays disclosed significant differences in the levels of Prekallikrein, Hageman Factor, Antithrombin-III, Prothrombin in survivors (N = 9) and fatal cases (N = 6) during the first week after admission. Since chromogenic peptide substrate assays are simple, cheap and easily automated, close monitoring of critical care patients may be rewarding.

Adult↗
PubMed1982

Prediction of prognosis in intensive care patients.

The treatment of intensive care patients is complex and sometimes unrewarding. The identification of factors that predict the outcome of these patients would make treatment easier to evaluate. Various pulmonary, cardiovascular and metabolic variables have been tested as prognostic measures. They have so far not been found conclusively reliable. It seems as if measurements of factors in the cascade systems, in particular prekallikrein, Hageman factor, and antithrombin III may be the best available indexes to predict a fatal outcome.

Acidosis↗
PubMed1981

Excretion of carcinoma products in irradiated C3H/He mice.

Local low-dose (200 rads) gamma-irradiation to both kidneys impaired the excretion of 3H-labeled tumor products and reduced the survival time of mice carrying carcinomas in the ascites form. Daily i.p. injections of cell-free ascites fluid into tumor-free mice for 3 weeks resulted in the death of 25 of 180 irradiated animals, with no deaths among 180 injected unirradiated controls. The only histologically visible effects of irradiation of the kidneys during ascites tumor growth or during i.p. injections of cell-free ascites fluid was a cloudy swelling of the tubular epithelium in the renal cortex together with excessive protein in the tubular lumens.

Animals↗