The heart rate performance curve and left ventricular function during exercise in patients after myocardial infarction.

PURPOSE: The aim of the study was to investigate the heart rate turn point (HRTP) in the time course of the heart rate performance curve (HRPC) in patients after myocardial infarction, and the relationship between the HRTP, the left ventricular function, and the second lactate turn point (LTP2). METHODS: We studied the degree and the direction of the HRPC and the left ventricular ejection fraction (LVEF) in 49 male patients 57 +/- 8 d after their first posterior wall infarction (MI). An incremental cycle ergometer test was performed and three phases of energy supply were defined (I: aerobic; II: aerobic-anaerobic transition; III: anaerobic) via blood lactate LA concentration. HRTP and LVEF-turn points (LVEFTP) were assessed by linear turn point analysis. The degree and direction of the deflection of HRPC were described as factor k (k > 0.1: downward deflection; -0.1 < k < 0.1: linear time curse; k < -0.1: upward deflection). The LVEF was determined by RNA. The difference between Pmax and LTP2 was calculated for LVEF (delta LVEF). RESULTS: An HRTP could be found in 44 and a LVEFTP in 47 cases. The HRTP occurred at 85 +/- 17 Watt (W), which correlated (r = 0.95; P < 0.001) with the LTP2 (84 +/- 17 W) and the LVEFTP (84 +/- 17 W, r = 0.93; P < 0.001). From LTP2 to Pmax a significant decrease in LVEF was found. There was a correlation between the percentage of HRmax at the HRTP and k (r = 0.70), as well as delta LVEF (r = 0.56). CONCLUSIONS: To prevent myocardial overloading, it seems to be useful to determine the HRTP, which indicate the workload where LVEF decreases.

Left ventricular function in response to the transition from aerobic to anaerobic metabolism.

The purpose of this investigation was to study myocardial function at rest, during three phases of energy supply, and during recovery. Radionuclide angiography was performed during the aerobic phase (phase I, rest-first lactate increase), the aerobic-anaerobic transition phase (phase II, first lactate increase-second lactate increase), the anaerobic phase (phase III, second lactate increase-maximal work performance (Pmax)), and during recovery. Thirty-eight male patients (59 +/- 7 d after myocardial infarction) were compared with 19 healthy control subjects and 21 sport students of comparable age. Left ventricular ejection fraction (LVEF) increased from rest to phase I and from phase I to phase II in sports students and control subjects. During phase III, LVEF did not change significantly in sports students, but it decreased significantly in control subjects. This is in contrast to the patients, who showed an increase of LVEF from resting values (47 +/- 3%) to phase I (50 +/- 1%), no change during phase II (51 +/- 2%), and a decrease to resting values (45 +/- 2) during phase III. All subjects showed an increase in stroke volume (SV) during phase I and II, reaching a maximum at phase II. This was evidenced by an improvement of the systolic function with a constant left ventricular end-diastolic volume (EDV) in control subjects and sports students. In contrast, an improved SV in patients was achieved through an increase in EDV and a less distinct increase in the left ventricular end-systolic volume (ESV). Maximal LVEF values were measured during the first 90 s of recovery in all subjects. Values during recovery are not representative of load dependent myocardial function. This increase in LVEF does not cause an increase in cardiac output but is a consequence of changes in the EDV and ESV, which decrease again immediately after the end of exercise performance.

Serum cytokines in juvenile rheumatoid arthritis. Correlation with conventional inflammation parameters and clinical subtypes.

OBJECTIVE: To examine the usefulness of determining extended serum cytokine profiles in patients with juvenile rheumatoid arthritis (JRA), for the purpose of improving differential diagnosis and monitoring disease activity. METHODS: In a 2-year prospective study, serum levels of interleukin-1 beta (IL-1 beta), soluble IL-2 receptor (sIL-2R), IL-6, IL-8, tumor necrosis factor alpha (TNF alpha), and the p55 soluble TNF receptor (sTNFR) were repeatedly determined by enzyme-linked immunosorbent assay in 40 patients with JRA, 13 patients with postinfectious arthropathies, and 30 healthy controls. The data were compared with conventional parameters of inflammation, such as C-reactive protein (CRP), iron and hemoglobin levels, erythrocyte sedimentation rate (ESR), white blood cell (WBC) counts, and platelet counts. WBC subsets were analyzed by flow cytofluorometry. RESULTS: At the first visit and at the peak of inflammatory activity according to CRP levels and/or ESR, serum levels of sIL-2R, IL-6, and sTNFR in JRA patients correlated significantly with conventional inflammation indicators, whereas IL-1 beta, IL-8, and TNF alpha did not. No changes in leukocyte subset distribution were noted. Among the different clinical subtypes of JRA, sIL-2R, IL-6, and sTNFR values at the time of the initial visit showed a pattern similar to CRP, whereby patients with systemic disease exhibited by far the highest values. TNF alpha and IL-1 beta were variably elevated in certain JRA subtypes. Patients with postinfectious arthropathies showed elevated levels of CRP, sIL-2R, TNF alpha, and sTNFR, which did not differ significantly from levels in the various JRA subtypes with the exception of systemic disease. Detailed analysis of types I and II pauciarticular JRA revealed that levels of CRP, IL-1 beta, and TNF alpha were elevated in patients with type I disease. While these parameters were invariably normal in patients with type II disease, sTNFR and sIL-2R were still found to be significantly elevated. Followup studies suggested that persistently high sTNFR values are a better indicator of JRA activity than are measurements of other cytokines or CRP. CONCLUSION: JRA is associated with significant and consistent changes in serum levels of inflammatory cytokines and soluble receptors. For the clinical monitoring of JRA, determination of levels of sTNFR, and to some extent sIL-2R, may be particularly useful, since these determinations yield information about subtype and/or activity of disease that is not available from conventional parameters of inflammation.

[Quality control of blood components by means of flow cytometers]. / Qualitätskontrolle von Blutkomponenten mittels Durchflusszytometer.

Small numbers of leukocytes cannot be counted by automated methods. So we performed fluorescent staining of leukocyte DNA and analyzed 50 samples of single-donor PC by FACS. In 72% of these PC we found white blood cells (WBC) < 5/microliter = WBC < 10(6)/U. Nevertheless we do filter our PC. Should fresh frozen plasma (FFP) be irradiated for immunocompromised patients to prevent TA-GvHD? To evaluate the number and distribution of WBC in FFP we stained WBC with moAb and performed FACS analyses. We found WBC 7.164 +/- 5.66 x 10(6)/U, lymphocytes, 3.032 +/- 3.66 x 10(6)/U and T lymphocytes 2.135 +/- 2.02 x 10(6)/U. According to these data it should be considered to irradiate FFP for immunocompromised patients.

Single dose of filgrastim (rhG-CSF) increases the number of hematopoietic progenitors in the peripheral blood of adult volunteers.

Hematopoietic progenitor cell levels were monitored in the peripheral blood of ten healthy adults receiving a single dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF). The objective was to determine the time and number of progenitor cells released into the peripheral blood, induced by a single dose of 15 micrograms/kg rhG-CSF administered intravenously. In all cases the absolute number of circulating progenitor cells including granulocyte-macrophage and erythroid lineages increased up to 12-fold (median 9.4-fold) 4 days after treatment. These findings were based on flow cytometric quantification of CD34+ cells and on progenitor assays. The relative distribution of granulocyte/macrophage and erythroid progenitors remained unchanged. rhG-CSF was well tolerated; mild to moderate bone pain was the most common side-effect and was noted in 6 of 10 subjects. Thus a single dose of rhG-CSF is effective in mobilizing progenitor cells into the peripheral blood in healthy adults. If these progenitors are capable of reconstituting bone marrow, peripheral progenitor cell separation following rhG-CSF administration could be a reasonable alternative to conventional bone marrow harvest in healthy adults.

Peripheral blood lymphocytes of nonleukemic lymphoma patients exhibit aberrant expression of T-cell activation markers after polyclonal stimulation in vitro.

The authors evaluated suppressed in vitro functions of peripheral blood lymphocytes (PBL) as a possible tool in the early diagnosis of human lymphoma. In 13 of 22 patients with recent onset of various types of nonleukemic lymphomas (Mb. Hodgkin and non-Hodgkin's lymphomas of B-cell and T-cell origin) the mitogen response of PBL against phytohemagglutinin (PHA) and concanavalin A (Con A), as measured by 3H-thymidine (3HTdR) uptake, was found to be significantly suppressed, whereas the response to pokeweed mitogen (PWM) was normal in 18 cases. In parallel, cytofluorimetric analysis was done with PBL after 72 hours in culture with and without PHA, using antibodies against the differentiation antigens: CD3, CD8, CD4, CD19, and CDw14 and the activation antigens: interleukin-2 (IL-2) receptor (IL-2R, CD25), human leukocyte antigen DR (HLA-DR), and transferrin receptor (TR). Compared with healthy controls and patients with other diseases, a significant reduction of the total T-cell blast response, i.e., the percentage of large T-cells bearing activation markers, was found in all lymphoma cases including those with a normal 3HTdR uptake. Furthermore, a pronounced inhibition in the expression of the activation markers Il-2R and TR, but not of HLA-DR, was detected on CD3+ cells in PHA-stimulated PBL of all lymphoma cases. Thus, polyclonal activation combined with activation antigens seems to give more accurate information about the functional defect(s) of PBL in an early state of lymphoma; these parameters may therefore be valuable diagnostically. The abnormal pattern in the expression of T-cell activation antigens after polyclonal stimulation may help in the understanding the cellular immune defects associated with lymphoma.

[Suppression of lymphocyte function 2 years following surgical treatment of paranasal sinus mycosis]. / Suppression der Lymphozytenfunktion zwei Jahre nach operativer Behandlung einer Nebenhöhlenmykose.

Prior investigations showed that acutely diseased patients with an aspergillus sinusitis manifested immune dysfunctions in respect of both T and B lymphocytes. In contrast to patients with nonmycotic sinusitis reduced in vitro and in vivo responsiveness was observed. The aim of this study, carried out after removal of the fungus ball and endoscopic surgery in clinically healthy patients, was to ascertain whether this reduced responsiveness was to be regarded as the effect or cause of an Aspergillus fumigatus infection. Two years later, the in vivo response to recall antigens was normal in both groups of patients, whereas the response to mitogens (ConA, PHA and PWM) was still decreased in the aspergillus sinusitis groups. The data suggest that the reduced immune response is a consequence of the Aspergillus fumigatus infection. Depressed skin reactivity is only present during acute infection, while proliferative capacity, as measured in the "whole blood stimulation" assay is depressed for a long time after healing the acute infection.

Cytofluorimetric analysis of mitogen-activated peripheral blood lymphocytes of non-leukemic lymphoma patients reveals an abnormal disease-related expression pattern of activation antigens.

The purpose of this study was to examine patterns of peripheral T-cell-activation antigen expression after polyclonal in vitro stimulation in early stages of lymphoproliferative diseases. With 18 patients afflicted with recently diagnosed, non-leukemic stages of B and T cell lymphoma cytofluorimetric analysis was performed with peripheral blood lymphocytes (PBL) after 72 h in culture with and without phytohemagglutinin, using antibodies against the differentiation antigens CD3, CD8, CD4, CD16, CD19, CDw14, and the activation antigens interleukin-2 receptor (IL-2R, CD25), HLA-DR (DR), CD56 and transferrin receptor (TR). Compared to healthy controls and patients with other diseases, a very significant reduction of large T cells bearing activation markers was found in all lymphoma cases. Furthermore, a pronounced inhibition in the expression of the activation markers IL-2R and TR, but not of DR, was detected on CD3+ cells in phytohemagglutinin-stimulated PBL of all lymphoma cells independently of DNA synthesis, as measured by [3H]thymidine uptake. Determination of the natural-killer-cell-(NK)-associated antigens CD16 and CD56, available for our studies in a CD16 + CD56 combination kit, revealed, after phytohemagglutinin stimulation, significantly increased expression values in 8 lymphoma patients so far investigated, as compared to 12 healthy controls. Thus, polyclonal activation combined with cytofluorimetric screening of activation antigens seems to give useful information on the functional defect(s) of PBL in an early state of lymphoma, and may therefore be of considerable diagnostic value. The observed pattern of T cell activation antigen expression after phytohemagglutinin stimulation may give further clues to the understanding of immune dysfunction(s) associated with lymphoma.

[In vivo and in vitro suppression of lymphocyte function in paranasal sinus mycoses]. / In-vivo- und In-vitro-Suppression der Lymphozytenfunktion bei Nebenhöhlenmykosen.

In about 10% of patients operated on a chronic sinusitis, an aspergilloma is found in the paranasal sinus. To detect possible underlying immunodeficiencies, patients with aspergilloma were subjected to an immunological screening programme. The data were compared with those of patients suffering from non-mycotic chronic sinusitis and healthy controls. Totale lymphocyte counts and immunological levels were normal in both groups of sinusitis. Leukocyte subset analyses by membrane fluorescence revealed a significant decrease of CD11+ cells, i.e. macrophages/monocytes and NK cells, in both types of sinusitis. Furthermore, a markedly enhanced frequency of CD25+-cells, i.e. IL 2-receptor bearing cells, was observed in patients with aspergilloma. Peripheral blood lymphocytes of both groups of patients showed a significant reduction in the proliferative response to both T and B-cell mitogens, the values for the mitogens ConA and PWM being significantly lower in aspergilloma patients than in those with non-mycotic sinusitis. This lack of lymphocyte stimulation in the aspergilloma group was also manifest in skin tests to recall antigens. These first data suggest an immunodeficiency in association with chronic sinusitis caused by Aspergillus fumigatus. Further studies are needed to clarify if this defect is cause or result of the mycotic infection.

In vivo and in vitro suppression of lymphocyte function in Aspergillus sinusitis.

In about 10% of patients who are operated on for chronic sinusitis, an aspergilloma is found in the affected paranasal sinus. In order to detect possible underlying immune defects, 25 patients with aspergillomas were subjected to an immunological screening program. The data obtained were compared with those of patients with non-mycotic chronic sinusitis and healthy controls. Total lymphocyte counts and immunoglobulin levels were normal in both groups with sinusitis. However, leukocyte subset analyses using membrane fluorescence revealed a significant decrease of CD11+ cells (macrophages, monocytes and natural killer-cells) in both types of sinusitis. Furthermore, a markedly enhanced frequency of CD25+ cells (interleukin 2-receptor-bearing cells), was observed in patients with the aspergillomas. Additionally, peripheral blood lymphocytes in both groups of patients showed a significant reduction in the proliferative response to both T- and B-cell mitogens, with the values for the mitogens ConA and PHA being significantly lower in the aspergilloma patients as compared to those with non-mycotic sinusitis. This lack of lymphocyte stimulation in the aspergilloma group was also manifest in skin tests to recall antigens. These first data suggest that there is an immune deficiency in patients with chronic sinusitis caused by Aspergillus fumigatus. Further studies are needed to clarify if this defect is the cause or the result of the mycotic infection.

[A fluorescence-activated cell sorter--analysis of peripheral T lymphocyte subpopulations in psoriasis]. / FACS--Analyse peripherer T-Lymphozytensubpopulationen bei Psoriasis.

By means of the fluorescence activated cell sorter (FACS), we analyzed the T-lymphocyte subpopulations in peripheral blood samples from 82 patients showing various clinical manifestations of psoriasis. With regard to both the absolute values of T-helper and T-suppressor cells and those of the T-helper/T-suppressor cell ratios, there were no quantitative differences between the patients (i.e. either the entire collective of classified according to the various forms of psoriasis) and the control group. We discuss the pathophysiological relevance of peripheral and in situ analyses of T-lymphocyte subpopulations.

Testing for human immunodeficiency virus (HIV-1) antigens in haemophiliacs positive for HIV antibody.

Sera collected from 28 haemophiliacs during the 2 years from 1985 to 1987 were examined for the presence of human immunodeficiency virus (HIV-1) antigen by two different methods using commercially available test kits. Of 28 patients, 18 had been positive for HIV antibody since at least 1985 and their HIV infection by blood products went back 3-6 years. Of these 18 antibody-positive patients, 8 were positive for HIV antigen according to one or both antigen tests on one or more occasions. The longest period of antigen expression was 21 months in two patients, one being in perfect health, the other showing AIDS-related complex (ARC) for the last 9 months. The detection of antigen expression was highly variable between the two tests used. Both positive and negative antigen-test results must therefore be used with great caution in clinical practice.

[Evaluation of drugs with questionable effectiveness and so-called natural preparations in oncology by patients. Results of a survey]. / Beurteilung von Medikamenten mit fraglicher Wirksamkeit und sogenannten Naturheilmitteln in der Onkologie durch den Patienten. Ergebnisse einer Umfrage.

In a questionnaire with 295 out-patients with gynecological cancers 51% had undergone paramedical treatment. This medication was given additionally to traditional treatment. The effect of paramedical proceedings was supposed to be good in most of the patients.

[Effectiveness of tumor follow-up in gynecology]. / Zur Effektivität der Tumornachsorge in der Gynäkologie.

Tumor recurrences can be detected earlier than in former times by new biochemical and radiological methods. Recurrences could be suspected in 35 (30.4 per cent) of 115 oncological patients 6 months before their clinical manifestation by determination of elevated levels of tumor markers in the serum. In the following time in all cases the suspicion could be proved with computed tomography.

[HTLV-III antibodies and immunologic changes in hemophilic children. Prevalence of HTLV-III antibodies in hemophilic children and their relatives living in the same household]. / HTLV-III-Antikörper und immunologische Veränderungen bei hämophilen Kindern. Prävalenz von HTLV-III-Antikörpern bei hämophilen Kindern und deren im selben Haushalt lebenden Verwandten.

19 (51%) of 37 hemophiliac children and adolescents regularly treated with factor VIII and IX concentrates were positive for HTLV III antibodies. The prevalence of HTLV III antibodies was higher in patients with severe hemophilia (64%) requiring frequent administration of concentrates than in patients with mild hemophilia (17%). No patient showed signs of AIDS or AIDS related complex. Immunologic alterations (inverse ratio of helper- and suppressor lymphocytes, elevated immunoglobulins, and elevated total serum proteins) were more often observed in patients requiring frequent administration of concentrates than in patients requiring relatively infrequent administration of concentrates. Since in patients frequently treated with concentrates the prevalence of HTLV III antibodies was also higher, it was not possible to draw any conclusions whether the observed immunologic alterations are due to the HTLV III infection alone or are also induced by the frequent administration of coagulation factor concentrates. No HTLV III positive person was detected in 45 relatives of 18 HTLV III positive hemophiliac children living together in 16 households and actively participating in the care of those children. In contrast, 6 (11%) of 55 relatives living in 21 households with 23 hepatitis-B-positive hemophiliac children were positive for hepatitis B. Our results support the general impression, that the risk to contract hepatitis B seems to be greater than to contract HTLV III from seropositive patients, and should help to facilitate the social integration of HTLV III positive hemophiliac children.

[Cyclosporin A as a diabetogenic cofactor]. / Cyclosporin A als diabetogener Kofaktor.

Two kidney transplanted patients are reported, who developed an insulin dependent diabetes mellitus after crossing therapeutic Cyclosporine A levels. After stabilisation of the Cyclosporine A levels the insulin dependent diabetes mellitus was completely reversible. The results are indicating Cyclosporine A as the insulin dependent diabetes mellitus initiator.

Radiological aspects of aspergillosis in the paranasal sinuses.

A retrospective radiographic study was performed on 142 proven cases of Aspergillosis in the paranasal sinuses. In all but two cases the mycosis was unilateral and in all cases the maxillary sinus was infected. A common radiographic presentation was a homogeneous opacity of the infected maxillary sinus, while about 50% of the cases showed nonspecific infectious changes of other paranasal sinuses additionally. Earlier stages of the disease showed an intraluminal soft tissue mass, representing the mycelium conglomerate. Bone destruction due to Aspergillosis could not be proven. 58% of the cases presented with intraluminal structures of metallic density. Histochemical studies proved these to consist mainly of tertiary Calciumphosphate. These concrements are considered to be pathognomonic of Aspergillosis.

[Sequential determination of circulating immune complexes in ovarian tumors]. / Sequentielle Bestimmung zirkulierender Immunkomplexe bei Ovarialtumoren.

We investigated sera from 39 patients with ovarian tumors with regard to the presence of circulating immune complexes, beginning at the time of diagnosis and further on through the course of disease. We were able to demonstrate circulating immune complexes by means of polyethylenglycolprecipitation. About 75% of the patients in the stages FIGO-ov I and FIGO-ov II showed increased values at the time of diagnosis. Following radical surgery they decreased to almost normal so during the time of remission. A relapse was proceeded by an increase up to 8 weeks before being detectable by clinical investigation. The stages FIGO-ov III and IV did not show a comparable correlation, however. Cases with benign cystic ovarian tumors did not show increased values. The precipitation by polyethylenglycol has been revealed to being a suitable screening method for early diagnosis of relapses.