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Biomedical subjects

H Sauer

Publications and source records attributed to H Sauer.

At least 307 records · Page 17Linked to original sources

Development of chronic hepatic porphyria (porphyria cutanea tarda) with inherited uroporphyrinogen decarboxylase deficiency under exposure to dioxin.

Exposure to dioxin triggered a clinically manifest chronic hepatic porphyria (porphyria cutanea tarda) in two patients (brother and sister) with hereditary uroporphyrinogen decarboxylase deficiency. The patients showed a decrease of erythrocyte uroporphyrinogen decarboxylase activity to approximately 50% of controls even in reinvestigations after three years, whereas clinical symptoms and porphyrinuria had improved considerably. Only a subclinical phase of chronic hepatic porphyria persisted. Subnormal uroporphyrinogen decarboxylase activity could be determined in altogether nine family members. The remission of porphyria cutanea tarda into a subclinical phase occurred after chloroquine therapy. Subclinical phases of chronic hepatic porphyria (type A) in other family members remitted without special therapy. Among the 60 persons dioxin-exposed by the Seveso accident, a secondary coproporphyrinuria was found in 22% of examined patients with transition to a subclinical chronic hepatic porphyria in 5 cases. The changes had subsided completely after one year. A persistence of the transition state in 3 cases is probably due to alcohol influence. None of these cases developed a porphyria cutanea tarda. The investigations showed that a hereditary disposition is necessary for biochemical and clinical expression of chronic hepatic porphyria after a unique dioxin exposure. This is not given in the sporadic cases: after a unique dioxin exposure they indeed develop a symptomatic disturbance of porphyrin metabolism but not a clinically relevant chronic hepatic porphyria. We conclude that a unique acute exposure to dioxin can trigger the chronic hepatic porphyria disease process in persons with an underlying genetic abnormality of uroporphyrinogen decarboxylase.

Adult↗

[Multiple image artifacts with linear sonic transducers].

The multielement arrays used nowadays for diagnostic purposes can, by means of digital signal processing, produce exact images with no problem. When physical limits were reached however, geometric image artifacts also became more evident, thereby making diagnosis more difficult or uncertain. Multiple images became especially evident during tests in the early stages of pregnancy, making it harder to differentiate between single and multiple pregnancies , particularly as dynamic processes such as the heart beat can be shown double at a certain phase in the pregnancy. Artifacts were also observed in the form of multiple echos during control checks on the position of intrauterine contraceptive devices and when investigating gynaecological tumors. These artifacts are ascribed to sonic behaviour at interfaces and are representable as a function of the sonic angle of incidence primarily in one plane--the cross section. They appear virtually symmetrical and can be wiped out by moving the sonic transducer. Although there is no problem in recognising the double phenomena as being artifacts in checks on the position of IUD's, all multiple structures should be clarified by suitable examination techniques especially during the early stages of pregnancy and with tumours.

Diagnosis, Differential↗

[Immunologic studies in patients with Crohn disease and ulcerative colitis].

To compare patients with Crohn's disease and patients with ulcerative colitis we have studied some immunological parameters (level of IgM, IgG and IgA in the serum, number of lymphocytes, E rosettes) and the immunological reactivity to antigens from colon carcinoma and to colon antigens prepared from healthy and from colon tissue altered by Crohn's disease (antigen specific rosette test, MEM-test, antibody titer). The results indicate a decreased proportion of T cells in both bowel diseases on the one hand, on the other hand a specific cell-meditated immune reaction to colon antigens could be observed in patients with Crohn's disease. In patients with ulcerative colitis such reactions are determined only in the acute phase of disease or in recidive. It remains to be elucidated whether these immunological reactions represent a basic pathogenetic factor in the onset of these diseases.

Antigens, Neoplasm↗

[The importance of active rosette-forming cells and specific antigen-binding cells in the diagnosis of rejection after allogeneic orthotopic kidney transplantation].

After allogeneic renal transplantation in 26 female pigs the kinetics of the immunological reactivity against the graft have been investigated with a specific test, the antigen specific rosette test and an unspecific test, the active E-rosette test. In acute and chronic rejection the level of antigen specific rosette forming cells reflects very well the clinical signs of rejection. Because of early occurrence of immunological reactivity in the case of frequent (daily) testing this test is suitable for a relative sure prediction of rejection episodes. In spite of their relative good correlations to the increase of serum creatinine, posttransplant increase and decrease of active rosette forming cells are not always in an uniform temporal relation to the rejection process. For that reason this test alone is not suitable for diagnosis of rejection. However, high preoperative values (greater than or equal to 18% active T cells) refer to an increased readiness to immunological reactivity of recipient against the graft and reflect contraindication to transplantation. If active rosette forming cells (greater than or equal to 18%) and antigen specific rosette forming cells show maxima at the same time, than follow in high significance strong cell mediated rejections. On this way the active E-rosette test completes the values of the antigen specific rosette test.

Animals↗

[Antigen-specific rosette inhibition test with autologous serum--a possibility for the detection of blocking factors in chronic rejection of allogeneic orthotopic kidney transplants].

After allogeneic renal transplantation in 26 female pigs the kinetics of the immunological reactivity have been investigated in order to diagnose a rejection crisis. The animals were not treated with immunosuppressive substances. The antigen specific rosette test is an useful parameter for estimation of immune reactions against a graft. Moreover, the inhibition of this test by autologous serum taken in the course of a chronic graft rejection is caused by blocking factors. Therefore this inhibition test would be suitable for an exact determination of specific immune reaction against the graft. By exclusion of false positive results by means of the rosette reaction test a high significant correlation between the antigen specific rosette formation and the clinical symptoms of the rejection could be observed. As long as blocking factors are protecting the graft against activities of immunocompetent cells respectively their effector molecules, recipient serum is able to inhibit the rosette formation. On the other hand a strong increase of rosette forming cells in a pig whose serum does not show an inhibitory activity is correlated with clinical symptoms of a rejection.

Animals↗

Problems of anal continence operations.

After operation for high rectal atresia, incontinence is common. The various operations that are used to cure incontinence can undoubtedly produce considerable improvement. Our own experience and the results published in the literature show that improvement in continence is mainly due to the creation of an elastic barrier that will induce the development of ampullary function in the neorectum. In this connection the mental development of the child is of great importance, as he or she has to become aware of the afferent impulses and act accordingly.

Adolescent↗

Methotrexate and methotrexate polyglutamates in human sarcoma metastases after high-dose methotrexate therapy.

The methotrexate concentrations in the lungs or cutaneous metastases of patients with osteogenic or soft-tissue sarcoma were determined at different times after a high-dose methotrexate therapy. The levels in the metastases were 0.964 to 2.96 X 10(-7) molar six to nine days after the end of MTX infusion. They were thus 7.8 to 28 times higher than the corresponding serum levels. At the same time, an appreciable rise of dihydrofolate reductase activity was observed in the metastases. After chromatographic separation over Sephadex G15, MTX polyglutamates could be demonstrated in all tumor samples investigated so far; these amounted up to 68.3% of the total MTX. Taking into account the slower efflux of MTX polyglutamates compared to unchanged MTX, a new hypothesis for the principle of action of high-dose methotrexate therapy is discussed: the very high MTX doses lead to such high intracellular MTX concentrations even in transport-resistant tumor cells that at least part of the MTX is converted into MTX polyglutamates. Unchanged MTX flows relatively rapidly out of the cells, whereas the MTX polyglutamates only break down very slowly and thus can be cytostatically effective over a long period of time.

Biotransformation↗

[Vitamin B12 as a regulator and methotrexate as an antagonist of folic acid metabolism. Pathophysiologic and clinical aspects].

Biochemical investigations show a decreased bioavailability of 5-methyl-tetrahydrofolic acid in vitamin B12 deficient human cell cultures and bone marrow cells. Tetrahydrofolic acid cannot be liberated from its storage form. This so-called methyl-folate-trap results in a functional folic acid deficiency which is the pathogenetic principle of the defect in the cell proliferation in patients with vitamin B12 deficiency. This knowledge of biochemical mechanisms leads to the identification of rare disorders in the metabolism of vitamin B12 and folic acid. After methotrexate treatment a rescue effect with its antidote Leucovorin can only be achieved, if the ratio antidote: methotrexate is at least 10:1. This ratio is important in cell cultures as well as in bone marrow cells in vivo. The results lead to a formula for the calculation of the optimal dosis to reach a secure rescue for individual patients after high-dose methotrexate treatment. This makes the high-dose methotrexate regimen a treatment modality for malignant tumors without any side effects.

DNA↗

[Bone marrow transplantation in adults in acute leukemia, aplastic anemia and paroxysmal nocturnal hemoglobinuria. Results of the Medical Clinic IIi of LMU (Ludwig-Maximilians University) Munich].

Eleven adults have been transplanted for various reasons between July 1979 and July 1982: 2 with aplastic anemia (AA), 1 with paroxysmal nocturnal hemoglobinuria (PNH), 8 with acute leukemia (AL). Four patients suffered from acute lymphocytic leukemia (ALL) and four from acute non-lymphocytic leukemia (ANLL). Two of them were transplanted in relapse, 1 in a partial remission, and 5 in complete remission. All patients were in their late stage of disease. The PNH-patient had an identical twin, 8 patients had an HLA- and MLC compatible sib, 1 an unrelated donor, and 1 was transplanted from his father. Four patients are alive, 2 more than 3 years: 1 with AA and 1 with ALL who was transplanted in relapse. Six patients died of infectious complications (4 of interstitial pneumonia, 1 of a candida sepsis, 1 of acute toxoplasmosis). Patients living more than 3 weeks had a take. Acute graft-versus-host (GvH) disease did not present a major problem. All patients received methotrexate for GvH-prophylaxis, in three instances the marrow was additionally pre-incubated with anti-T-cell globulin.

Acute Disease↗

Treatment and metabolic findings in extreme short-bowel syndrome with 11 cm jejunal remnant.

A full term girl survived nonresected, subtotal small-bowel gangrene. The length of the small-bowel remnant (only jejunum) measured 11 cm. Anastomosis was performed with insertion of a 3-cm-long antiperistaltic segment. The ileocecal valve remained intact. The jejunal remnant showed an increase in length of at least 1 m. The resorptive functions of the bowel residue recovered incompletely, particularly the ileal functions. Disturbances of calcium and phosphorus metabolism are now in the foreground; nevertheless, the child now manages to live without parenteral feeding.

Female↗

First rank symptoms as predictors of ECT response in schizophrenia.

First rank symptoms (FRS) in association with affective features predict improvement on ECT. When affectivity was disregarded in 142 schizophrenic probands given ECT and the relationship between FRS alone and ECT response examined, those without FRS had a significantly better ECT outcome score than those with FRS. In various schizophrenic sub-samples, defined in terms of hypothesized predictive abilities of different sets of FRS, no differences came to light.

Electroconvulsive Therapy↗

[Employment of the antigen-specific rosette test in the diagnosis of rejection following allogeneic orthotopic kidney transplantation in the pig].

Investigations of the course were performed by means of an antigenspecific rosette test using a poolantigen from tissue samples of approximately 100 pigspleens with the help of the model of allogenic renal transplantation in 26 female pigs. The animals received no immunosuppressive treatment. In our study with this test 75% all of the rejection episodes by clinical acute and chronic rejection were predictably. In acute rejection a maximum rosette forming cell response was examined in general 2-3 days before a pathological rise of serum creatinine or in the course of a bad clinical state. Under chronic rejection this reaction can be seen 5-14 days before the kidney function will go poor. In spite of the high individuality of original curves statistical analyses indicate a good correlation of the number of antigenbinding cells toward pathological deviation of serum creatinine, as long as blocking factors not protect the transplant against the attack of persisting immunocompetent cells or their effectors. These blocking factors can be monitored in a rosette inhibition test with autolog serum.

Animals↗

Results of postoperative treatment of ileus in infants and children by means of gastrocecal tube splinting of the intestine.

Since 1966, gastrocecal tube splinting of the small intestine has been used in 77 instances of postoperative ileus, the over-all mortality being 5.2 per cent. Six to seven patients in whom the operation had been performed at least one year ago, a mean value of 3.5 years, had follow-up examinations. One child had a recurrence of ileus, and in one patient, postoperative invagination was observed. Seventy per cent of the children having follow-up examinations were completely asymptomatic, 24 per cent had slight complaints and 6 per cent did not respond. The method described can, therefore, be recommended for the prevention and therapy of postoperative ileus, provided these contraindications are observed: severe disturbances of intestinal circulation; enterocolitis and ulcerations of intestinal mucosa; meconium ileus, in primary operations, and gastroschisis, in primary operations.

Child↗

Pharmacokinetics of erythrocyte methotrexate after high-dose methotrexate.

Erythrocyte methotrexate (MTX) concentrations were determined in 10 patients with metastatic osteogenic or soft tissue sarcoma after 52 cycles of high-dose methotrexate (HDMTX). In contrast to serum MTX, pharmacokinetics of erythrocyte MTX showed three distinct phases: A rapid decrease to a nadir 2-3 days after MTX was followed by a significant rise of erythrocyte MTX until days 10-14. Subsequently there was a third phase, with a definite decrease of erythrocyte MTX concentrations with half-lives of 30-40 days. Short-term repititions of HDMTX had considerable influence on the first two phases of the kinetics. Each curve surpassed that of the previous therapy, and erythrocyte MTX concentrations increased continuously to the values measured at the end of the HDMTX infusion. The following mechanisms of MTX enrichment in erythrocytes is discussed: In erythro- and normoblasts MTX is converted to polyglutamate forms, which are retained inside the cell and are probably the reason for the relatively high sensitivity to MTX. Upon resumption of erythropoiesis the release of freshly prepared erythrocytes containing MTX and predominantly MTX polyglutamates causes the renewed increase in blood MTX levels.

Adult↗

[Adriamycin and autologous bone marrow transplantation. Preclinical studies in dogs (author's transl)].

We investigated the toxicity of adriamycin (ADM) in dogs with regard to autologous bone marrow transplantation (BMT). Gastrointestinal toxicity limited the dose of ADM in single administration (3.0 mg/kg) and chronic cardiotoxicity in repeated administration (9 X 1.5 mg/kg every two weeks). The recovery of hemopoiesis was complete within 25 days after single and repeated doses of ADM as indicated by the restoration of blood counts and concentration of hemopoietic precursors (CFUc) as well as proliferate activity of bone marrow. At this time bone marrow was obtained and reinfused after total body irradiation (TBI) with 10 Gy. Single and repeated doses of 1.5 mg/kg ADM did not delay recovery of blood counts after autologous BMT as compared to transplantation of untreated marrow - in contrast a single dose of 3.0 mg/kg ADM did. Our results indicate that toxicity of ADM is not influenced by autologous BMT. Previous shorter therapy with conventional doses of ADM does not preclude autologous BMT.

Animals↗