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Biomedical subjects

J Grimm

Publications and source records attributed to J Grimm.

At least 55 records · Page 3Linked to original sources
PubMed1998

Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta.

Control of stability of beta-catenin is central in the wnt signaling pathway. Here, the protein conductin was found to form a complex with both beta-catenin and the tumor suppressor gene product adenomatous polyposis coli (APC). Conductin induced beta-catenin degradation, whereas mutants of conductin that were deficient in complex formation stabilized beta-catenin. Fragments of APC that contained a conductin-binding domain also blocked beta-catenin degradation. Thus, conductin is a component of the multiprotein complex that directs beta-catenin to degradation and is located downstream of APC. In Xenopus embryos, conductin interfered with wnt-induced axis formation.

Adenomatous Polyposis Coli Protein↗
PubMed1998

Soluble interleukin-2 receptor serum levels after allogeneic bone marrow transplantations as a marker for GVHD.

Acute GVHD (aGVHD) is one of the major problems after allogeneic BMT. The diagnosis of aGVHD is difficult to establish, relying mainly on clinical evaluations and symptoms of aGVHD, often resembling those of organ toxicity, infection or drug rash. In 21 patients after BMT several serum cytokine levels (soluble interleukin-2 receptor (sIL-2R), sTNF-R, SCF, IL-6, IL-8, G-SCF and ICAM-1) were determined in order to evaluate their value as an indicator for aGVHD. The maximum levels of sIL-2R (and none of the other evaluated cytokines) correlated significantly (r = 0.8, P = 0.008) with the severity of aGVHD. We also found a significant correlation between the day of engraftment (neutrophil count >0.5 x 10(9)/l) and the severity of aGVHD (r = 0.5, P = 0.03): engraftment was earlier in patients without aGVHD (median of day 11) than in those with aGVHD (median of day 18). No correlation between sIL-2R and fever or organ toxicity could be found. Our data suggest that the sIL-2R level might be an indicator for aGVHD, reflecting the severity of the disease. In patients with late engraftment the risk of aGVHD seems to be increased, therefore these patients especially should be monitored closely, possibly using sIL-2R levels.

Adolescent↗
PubMed1997

Long-term follow-up of leukaemia patients after related cryopreserved allogeneic bone marrow transplantation.

We have previously shown that allogeneic bone marrow transplantation (BMT) with cryopreserved donor marrow cells can be used without prolonging the engraftment time or interfering with the reconstitution of haemopoiesis. In this report we extend our initial observations of the first 40 patients who underwent allogeneic bone marrow transplantation from related donors with cryopreserved donor bone marrow for haematological malignancies, including the long-term follow-up data of the previously reported patients. The outcome of these patients was compared with that of 40 related BMT recipients receiving fresh donor bone marrow (historic control group). Time until engraftment of all patients receiving cryopreserved bone marrow was not different from the control group (ANC > 0.5 x 10(9)/l 17d (range 11-24 d) versus 17.5 d (range 10-28 d): platelets > 20 x 10(9)/l 21 d (range 11-85 d) versus 22 d (range 13-69 d), respectively). There was the same incidence of acute and chronic GvHD in patients receiving either cryopreserved bone marrow or fresh bone marrow (acute GvHD > or = II 61% v 60% and chronic GvHD 56% v 52%, respectively). Chimaerism studies showed no difference between the patient groups. Furthermore, the two groups did not differ in day 100 survival (82% v 72%). With a median follow-up of 520 d (range 47-1365 d) and 1289 d (range 48-1849 d), 60% of the patients receiving cryopreserved and 53% of the patients receiving fresh allogeneic donor bone marrow, respectively, are alive. We conclude that cryopreservation of allogeneic related donor bone marrow does not adversely affect engraftment, does not decrease the incidence of severe acute GvHD, and does not seem to affect the day 100 survival or long-term haemopoiesis.

Adolescent↗
PubMed1997

Antimycotic therapy with liposomal amphotericin-B for patients undergoing bone marrow or peripheral blood stem cell transplantation.

Suspected deep or systemic mycosis in patients undergoing high-dose therapy and autologous or allogeneic bone marrow transplantation (BMT) requires an immediate systemic antimycotic therapy. Intravenous therapy with the standard drug conventional amphotericin-B is associated with severe adverse effects like nephrotoxicity and chills. Furthermore, BMT patients often receive other potential nephrotoxic drugs such as CsA or virustatics. In this study, we report 74 BMT-patients treated with liposomal amphotericin-B for culture-documented aspergillosis (n = 5) or candidiasis (n = 6), or for serologically (n = 35) or clinically suspected mycosis or as prophylaxis (n = 2). Therapy was initiated with a median dose of 2.8 (0.64-5.09) mg/kg body-weight and continued for 13 (1-55) days. The drug was excellently tolerated and only in one was therapy stopped due to severe chills and fever. Severe organ impairment was not observed under therapy with liposomal amphotericin-B. Creatinine decreased in five patients after an increase under preceding therapy with the conventional formulation. Influence of liposomal amphotericin-B on bilirubin and transaminases was difficult to evaluate due to therapy-related toxicity, veno-occlusive disease (VOD), and graft-versus-host disease (GvHD). 10/11 culture-positive patients died from aspergillosis (5/5) or candidiasis (5/6), but in 9/11 of these subjects the immunity was additionally compromised by GvHD, steroid therapy, and VOD. Liposomal amphotericin-B was effective in preventing relapse of systemic mycosis in 10/12 patients with a history of aspergillosis (n = 11) or candidiasis (n = 1). We conclude, that favourable toxicity of liposomal amphotericin-B should encourage dose escalation studies of liposomal amphotericin-B randomised against the conventional formulation and that the comparison of patients undergoing BMT with patients under standard chemotherapy might be difficult because of additional risk factors of the BMT-patients.

Adolescent↗
PubMed1997

High dose chemotherapy with busulfan, cyclophosphamide, and etoposide as conditioning regimen for allogeneic bone marrow transplantation for patients with acute myeloid leukemia in first complete remission.

We explored the combination of busulfan/cyclophosphamide/etoposide as conditioning regimen prior to bone marrow transplantation in 31 patients with acute myeloid leukemia (AML) in first complete remission. The preparative regimen consisted of 16 mg/kg busulfan, 30-60 mg/kg VP-16, and 120 mg/kg cyclophosphamide. With a median follow-up of 30.5 months (range, 5-60 months), 25 patients are alive in continuous complete remission. Estimated disease-free survival at 5 years is 80.5%. Death was due to transplant-related toxicity (graft-versus-host disease and cytomegalovirus infection, graft-versus-host disease and pneumonia, sepsis and mucositis, respectively). None of the patients have relapsed. As demonstrated by the results of this analysis, the conditioning regimen busulfan/cyclophosphamide/etoposide is effective and well tolerated in patients with AML in first complete remission. Main nonhematological toxicities were mucositis and hepatotoxicity. The low mortality and relapse rate appears to justify allogeneic bone marrow transplantation for patients with AML in first complete remission who have an HLA-identical donor. Whether this regimen offers a substantial improvement in disease-free and overall survival over presently used regimens warrants further investigation.

Acute Disease↗
PubMed1996

Prospective 12-year follow-up study of clinical and hemodynamic sequelae after deep vein thrombosis in low-risk patients (Zürich study).

BACKGROUND: No prospective study of the long-term sequelae of more than 10 years after acute deep vein thrombosis exists so far. Therefore, 58 low-risk patients with DVT were included in a prospective study to evaluate the natural history of postthrombotic syndrome. METHODS AND RESULTS: Clinical and hemodynamic examinations were performed at the time of admission; after 3, 6, and 12 months; after the 2nd, 3rd, 4th, 5th years; and finally after the 12th year. All patients received heparin initially and oral anticoagulants subsequently. After 12 years, 64% of the patients exhibited normal findings. Mild skin changes were found in 28%, marked trophic changes in 5%, and only one venous ulcer occurred. Regular use of compression stockings was reported by 54% of the patients with multilevel thrombosis. Although mean maximum venous outflow was significantly reduced from the acute event to 12 years later (P<.003) compared with the contralateral leg, a significant (P<.05) improvement was observed 6 months later. Recanalization of calf vein thrombosis was detected by Doppler sonography after 3 months. Sixty-four percent of the multilevel thromboses were recanalized completely or in part after 1 year; in 69%, valvular incompetence was found. CONCLUSIONS: In contrast to earlier reports, this prospective study up to 12 years after deep vein thrombosis demonstrates a low incidence of postthrombotic syndrome by administration of oral anticoagulants and regular compression therapy. However, the adverse clinical event rate (mortality 14%) and a recurrence rate of 24% show that the prognosis after deep vein thrombosis does not appear favorable even in low-risk patients.

Administration, Oral↗
PubMed1995

Separation and characterization of mobilized and unmobilized peripheral blood progenitor cells by counterflow centrifugal elutriation.

Peripheral blood stem cell (PBSC) harvests are highly contaminated with lymphocytes. In allogeneic transplantations with PBSC, this might lead to an increased risk of graft-vs.-host disease (GVHD). Marrow graft T cells depletion (TCD) by counterflow centrifugal elutriation (CCE) has been performed to decrease the incidence of GVHD, but in some cases, it has also led to a reduction in the PBSC content of the graft due to the distinct elutriation properties of these cells. We studied the ability of CCE to deplete lymphocytes from recombinant human granulocyte colony-stimulating factor (rhG-CSF)-mobilized PB mononuclear cells (PBMNC) and from unmobilized PBMNC from healthy volunteers. We characterized the elutriation properties of circulating mobilized and unmobilized hematopoietic progenitors. With an experimental three-flow rate CCE procedure, originally described for separation of bone marrow, fractions 24, 28, and Rotor Off (RO) were obtained without impairing yield or viability. This CCE procedure can also be used for the separation of PBMNC harvests by reducing the T cell contamination to or below the range seen in bone marrow grafts; CD3+ cell contamination in the RO fractions of mobilized and unmobilized PBMNC was reduced to < 10% of the input. This could bring allogeneic PBSCT within the range of feasibility. In unmobilized PBMNC, 25% of the recovered CD34+ cells were found in fraction 24, where no colonies were detected, and 50% of the recovered CD34+ cells were found in fraction RO, where most of the colonies were detected. In mobilized PBMNC, 80% of the recovered CD34+ cells were found in fraction RO, together with 90% of the colonies, but almost no colonies or CD34+ cells were detected in fraction 24. CD34+ cells in fraction 24 expressed less CD13, and antigen found on more mature myeloid cells. Mobilization with rhG-CSF causes a shift of CD34+ cells from smaller cells (fraction 24) to larger cells (fractions 28 and RO).

Antigens, CD↗
PubMed1994

Bone metastasis from cervical cancer.

BACKGROUND: This retrospective analysis examines the frequency, distribution, and the pattern of disease progression of bone metastasis in patients treated for cervical cancer and the use and results of palliative intent radiation therapy. METHODS: Charts, films, and other available records were reviewed for the 41 patients with bone metastasis of the 496 patients with invasive cervical cancer treated at the Gershenson Radiation Oncology Center, Detroit, Michigan, from 1980 through 1989. RESULTS: Several patterns of bone metastasis were observed: (1) direct extension into bone from the parametrial extensions of the primary or recurrent pelvic tumor, (2) direct extension into bone from parenchymal metastasis to distant lymph nodes or lung, (3) regional hematogenous metastasis compatible with Batson's venous plexus distribution, and (4) systemic hematogenous metastasis to distant bones. Eighty percent of the patients were irradiated, and of those, 70% experienced pain relief. CONCLUSIONS: Bone metastasis in patients with cervical cancer is an infrequent but significant occurrence with associated severe dysfunction, other signs of local and distant failure, and short life expectancy. Radiation therapy provides moderate palliation for treatable patients.

Adenocarcinoma↗
PubMed1994

Clinical significance of coronary flow reserve: effect of papaverine and exercise.

BACKGROUND: The clinical significance of coronary flow reserve (CFR) was evaluated after pharmacological (papaverine) and physiological (exercise) vasodilation in patients with coronary artery disease (CAD). METHODS: CFR was determined using parametric imaging in 10 patients with normal coronary arteries (group 1) and in 10 with CAD (group 2). Contrast density and mean appearance time were measured (region of interest = 249 pixels) in the perfusion beds of the left circumflex and the left anterior descending coronary arteries at rest, 45 s after 10 mg intracoronary papaverine, and during supine bicycle exercise. CFR was calculated from coronary perfusion after papaverine divided by perfusion at rest and coronary perfusion during exercise divided by perfusion at rest. Perfusion zones in patients with CAD were subdivided into regions supplied by a non-stenosed (group 2a) and a stenosed (group 2b) coronary artery. RESULTS: In control patients, heart rate increased from 75 beats/min at rest to 125 beats/min during exercise, and in patients with CAD from 63 to 107 beats/min, respectively. Mean aortic pressure showed a significant increase during exercise in both groups. Mean pulmonary artery pressure increased significantly during exercise from 19 to 28 mmHg in control patients and from 22 to 42 mmHg in the CAD group (P < 0.001). Coronary driving pressure (mean aortic minus diastolic pulmonary artery pressure) tended to increase during exercise in the control group (from 90 to 101 mmHg, NS) and remained nearly unchanged in patients with CAD (from 92 to 94 mmHg, NS). In the control group, CFR was significantly higher during exercise than after papaverine (4.0 versus 3.5, respectively; P < 0.01). However, coronary resistance (coronary driving pressure divided by coronary flow index) was similar after papaverine and during exercise. In patients with CAD, papaverine-dependent CFR was significantly reduced in the perfusion zone of the stenosed (2.1) but not of the non-stenosed coronary artery (3.0). In contrast, CFR during exercise was significantly decreased in both perfusion zones (2.5 in non-stenosed arteries and 1.5 in stenosed vessels). CONCLUSIONS: In control patients, CFR is slightly but significantly larger during exercise than after papaverine because of the exercise-induced increase in coronary driving pressure. In contrast, CFR is smaller during exercise than after papaverine in patients with CAD, most probably as a result of secondary mechanisms such as exercise-induced narrowing of stenosed vessels or an increase in extravascular resistance. Thus, CFR based on papaverine appears to be of limited value for assessing the functional significance of a stenotic lesion.

Adolescent↗
PubMed1993

Is atrial pacing needed for determination of coronary flow reserve by parametric imaging?

Heart rate changes during determination of coronary flow by parametric imaging may influence the flow measurement. Thus, the question is whether atrial pacing is mandatory for determination of coronary flow reserve (CFR) by this technique. CFR was calculated by digital subtraction angiography (parametric imaging) in 10 patients (8 with coronary artery disease and 2 control subjects) during sinus rhythm and during atrial pacing. Flow measurements were determined in the perfusion region of the left anterior descending and circumflex coronary artery, both at rest and after maximal coronary vasodilation with 10 mg intracoronary papaverine. CFR was defined as coronary flow during hyperemia divided by coronary flow at rest. Spontaneous heart rate was 71 +/- 15 min-1 at baseline, 73 +/- 15 min-1 after papaverine injection and 85 +/- 10 min-1 during atrial pacing. Heart rate variations during coronary arteriography were 4 +/- 3 min-1 at baseline and 5 +/- 4 min-1 after papaverine administration. CFR was 2.61 +/- 1.01 during sinus rhythm and 2.67 +/- 1.05 during atrial pacing. Mean absolute difference in CFR between sinus rhythm and atrial pacing was 0.31 +/- 0.31 (12 +/- 10% of CFR during pacing). Spontaneous heart rate variations during coronary arteriography are not associated with significant changes in CFR. Thus, atrial pacing is not mandatory for the determination of CFR by parametric imaging.

Angiography, Digital Subtraction↗
PubMed1993

Rapid purification of rabbit reticulocyte lipoxygenase for electron paramagnetic spectroscopy characterization of the non-heme iron.

An efficient three-step purification technique has been developed for the reticulocyte 15-lipoxygenase from rabbit. Ammonium sulfate fractionated reticulocyte lysate was purified by size exclusion chromatography and preparative scale isoelectric focusing. The entire procedure was complete in less than eight hours and was carried out in batches which typically yielded 10 mg of purified enzyme. The identity and purity of the enzyme were evaluated by N-terminal sequencing, sodium dodecylsulfate polyacrylamide gel electrophoresis and specific activity determinations. The enzyme contained approximately one g-atom iron per mole of protein. The iron was present in an electron paramagnetic spectroscopy (EPR) silent, presumably high spin iron(II), form in the isolated enzyme. Treatment with one equivalent of 13-hydroperoxy-9(Z),11(E)-octadecadienoic acid resulted in the appearance of an EPR signal around g6.

Animals↗
PubMed1993

Regional diastolic dysfunction in postischaemic myocardium in calf: effect of nisoldipine.

OBJECTIVE: The aim was to assess the effect of nisoldipine on left ventricular systolic and diastolic function during prolonged myocardial ischaemia. METHODS: The left circumflex coronary artery was ligated for 2 h and reperfused for 4 h in 12 calves. The animals were randomised to a control group (n = 6) or to treatment with 1.25 mg.h-1 intravenous nisoldipine (n = 6) during 2 h of ischaemia. Circulatory support by a ventricular assist device was performed throughout the experiment except for the time of haemodynamic measurements. Regional wall thickening of a normal and an ischaemic left ventricular region was determined using pairs of ultrasonic crystals. Left ventricular pressure was measured by micromanometry. Left ventricular wall thickness and regional wall stiffness at a common preload of 10 mm Hg were calculated using an elastic model with shifting asymptote. RESULTS: Ten animals survived after 6 h. No difference was observed in systolic function between controls and nisoldipine treated animals. Systolic thickening of the ischaemic wall remained depressed 4 h after reperfusion and showed some recovery after dopamine infusion. Ischaemic wall stiffness at a common preload was lower after nisoldipine during ischaemia and reperfusion than in controls. Control wall stiffness remained unchanged during the whole experiment with and without nisoldipine. Diastolic thinning of the ischaemic wall was prevented by nisoldipine during ischaemia and after reperfusion. CONCLUSIONS: Prolonged myocardial ischaemia is associated with increased myocardial stiffness of the ischaemic wall. Mechanical unloading can help to bridge the acute phase but cannot prevent postischaemic diastolic dysfunction of the ischaemic wall. Nisoldipine has a beneficial effect on regional diastolic function during ischaemia and reperfusion by decreasing regional wall stiffness and preventing diastolic thinning of the ischaemic wall.

Animals↗
PubMed1992

[Digital subtraction angiography for the assessment of myocardial perfusion].

Coronary angiography does not only permit to evaluate the severity of coronary disease but also to assess coronary flow reserve in various myocardial perfusion areas by digital processing. Use of colour flow mapping allows the assessment of both, density as well as distribution velocity of contrast-medium (= parametric imaging). The advantage of this technique is given by the possibility to assess coronary flow reserve not only at rest but also under physiologic situations such as bicycle ergometry. Clinical investigations have shown that coronary flow reserve determined after papaverine administration does not correlate with physiologic conditions such as physical exercise.

Angiography, Digital Subtraction↗
PubMed1992

Effect of aortic valve stenosis (pressure overload) and regurgitation (volume overload) on left ventricular systolic and diastolic function.

In secondary hypertrophy from chronic pressure or volume overload, or both, systolic as well as diastolic abnormalities of left ventricular (LV) function have been described, but their relation has not been defined. In 58 patients with aortic valve disease (28 with aortic valve stenosis, and 30 with aortic regurgitation) and in 11 control subjects, LV biplane cineangiography was performed simultaneously with LV high-fidelity pressure measurements. LV ejection performance was assessed by ejection fraction, and diastolic function by the time constant of LV pressure decay, the early and late peak filling rates, and the constants of chamber (pressure-volume relation) and myocardial stiffness (stress-strain relation). In the entire cohort (n = 69), ejection fraction was inversely related to the time constant of LV relaxation (r = -0.58, p less than 0.001) and to the constant of myocardial stiffness (r = -0.62, p less than 0.001). Despite preserved systolic contractile function (as evaluated from the ejection fraction-mean systolic stress relation), abnormalities in LV diastolic function were present in 9 of 18 patients with pressure overload and 20 of 22 with volume overload. None of the 58 patients with aortic valve disease had a reduced early peak filling rate, whereas a reduction in late peak filling rate was observed in 3 with aortic stenosis, but in none with aortic regurgitation. This, it appears that abnormalities of relaxation and passive diastolic myocardial stiffness precede alterations in myocardial contractility. Assessment of peak filling rates is not helpful to detect diastolic dysfunction in patients with aortic valve disease.

Adolescent↗
PubMed1992

[Epiphyseal dysplasia of the hip joint, its diagnosis and differential diagnosis with MRT].

Sixteen hip joints of eight patients with multiple epiphyseal dysplasia were examined by clinical investigation, plain films and by magnetic resonance imaging (MRI), using T1- and T2-weighted images and gradient echoes. MRI is useful in demonstrating the congruity of the joint, in the changes of the epiphyseal signal intensities and the epiphyseal line. Individual changes of the signal intensity patterns on T1- and T2-weighted scans are described. Although MRI exhibits a variety of patterns in different patients, a clearcut differentiation from Legg-Calvé-Perthes' disease is possible.

Adolescent↗
PubMed1992

Oppositional defiant and conduct disorders: issues to be resolved for DSM-IV.

Oppositional defiant disorder (ODD) and conduct disorder (CD) are reasonably distinct both in terms of statistical covariation among symptoms and ages of onset. The two disorders are related in similar ways to impairment and family history of antisocial behavior, but the association is stronger for CD than ODD. Virtually all clinic-referred youths with prepubertal onset of CD have retained the symptoms of ODD that emerged at earlier ages. Furthermore, a set of serious antisocial behaviors characteristically emerges at later ages in some youths with CD, suggesting further developmental progression within CD. These findings are consistent with a conceptualization of ODD and CD as developmentally staged, hierarchically organized levels of severity of the same disorder, but two findings argue for distinguishing separate disorders in DSM-IV: (1) many youths with ODD never develop CD, and (2) CD that emerges for the first time in adolescence appears to be independent of ODD.

Acting Out↗
PubMed1992

[Osteochondrosis dissecans of the elbow joint].

Thirty-one elbow joints in 29 patients (28 males, only 1 female), operated on for osteochondritis dissecans, were available for follow-up after an average of 10 years. The mean age at diagnosis was 24.4 years, but 11 patients were younger than 20. In 23 out of 29 patients the right elbow was involved, including 2 cases with bilateral involvement. In 20 cases removing the free bodies was the only surgical procedure performed, but in 2 cases it was combined with resection of the radial head. At follow-up, only one-third of the patients had no complaints. Nevertheless, daily activity was not restricted for any of the cases. Degenerative arthritic changes were found in only a few cases. These results are illustrated by means of three typical cases, which are compared with six similar cases in the international literature.

Adolescent↗