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Biomedical subjects

M Grimm

Publications and source records attributed to M Grimm.

At least 19 recordsLinked to original sources
PubMed1998

Benign prognosis of early sinus node dysfunction after orthotopic cardiac transplantation.

Previous reports raised concern about the prognosis of patients with sinus node (SN) dysfunction after cardiac transplantation and led to a low threshold for permanent pacemaker (PM) placement at most institutions. The present study addresses the survival in patients with normal and impaired post operative SN function and the effect of permanent pacing with respect to overall and cardiac mortality. There were 120 patients with normal (corrected SN recovery time < 520 ms, group I) and 47 patients with imparied SN function (corrected SN recovery time > 520 ms and/or sinus arrest +/- escape rhythms). Pacing support was deemed unnecessary in 23 of 47 patients with SN dysfunction (group II; asymptomatic SN bradycardia and corrected SN recovery time 3,812 +/- 5,800 ms) while a total of 24 patients had PM placement a mean of 29 +/- 44 days after transplantation (symptomatic bradycardia or absence of sinus rhythm at discharge, group III). Patients were followed for a mean of 46.7 months. Thirty-five deaths occurred during the study period. Sixteen deaths were cardiac but none were causally related to the SN dysfunction (graft failure due to rejection or atheropathy n = 14; myocardial infarction n = 2). Four of these cardiac deaths were sudden and all occurred in the presence of widespread structural abnormalities (rejection/vasculopathy/myocardial infarction). SN dysfunction was not related to overall (P = 0.25) or cardiac mortality (P = 0.33). Regarding either endpoint, patients who had permanent PM placement did no better than their unpaced counterparts in group II (P = 0.53 and P = 0.33, overall and cardiac mortality, respectively). Likewise, survival did not differ between groups I and III for either endpoint (P = 0.77, P = 0.65, respectively). These data suggest that patients with mild SN abnormality, who are in sinus rhythm at the time of discharge, can be followed by observation without specific therapy.

Adult↗
PubMed1998

WAF1/p21 regulates proliferation, but does not mediate p53-dependent apoptosis in urothelial carcinoma cell lines.

The WAF1/p21 gene product is an inhibitor of cyclin-dependent kinases which can be induced by the tumor suppressor p53 and mediate some of its effects, or function in p53-independent pathways of cell cycle regulation. Although a potential tumor suppressor gene, WAF1/p21 is expressed in bladder cancer. To elucidate the function of p21 in tumor cells we have investigated in urothelial carcinoma cell lines: i) WAF1/p21 mRNA and protein expression, ii) the biological effects of p21 overexpression or down-regulation and (iii) whether p21 can be induced by p53. WAF1/p21 mRNA levels examined in four cell lines were comparable to bladder mucosa. One cell line, HT1376, failed to express p21 protein due to a frame shift mutation. Overexpression of WAF1/p21 cDNA inhibited clone formation in three cell lines, whereas transfection with antisense WAF1 increased clone sizes and numbers. WAF1 sense clones showed diminished cell proliferation compared to the parental cell line. Apoptosis- induced wild-type p53 was not inhibited by overexpression of antisense WAF1/p21. In a cell clone derived from line VMCub1 by stable transfection with wild-type p53 under the control of a metallothionein promotor, p21 was induced along with p53 upon activation of the promoter with zinc chloride. This induction was accompanied by a decrease in cell proliferation but by little apoptosis. These data suggest that p21 inhibits proliferation in a p53-dependent or independent manner but does not mediate p53-induced apoptosis in urothelial carcinoma cells.

Apoptosis↗
PubMed1997

Simultaneous heart and kidney transplantation as treatment for end-stage heart and kidney failure.

BACKGROUND: The aim of the present analysis was to define the role of simultaneous heart and kidney transplantation (HNTX) using organs from the same donor by evaluation of clinical strategy and achieved outcome compared with a reference group of concurrently single heart transplant (HTX) and kidney transplant (NTX) recipients. Compared with other organ combinations (pancreas-kidney, heart-lung), HNTX has been performed infrequently and is reported mainly as case records in the literature. Because of expansion of recipient selection criteria for HTX and NTX, the number of patients requiring simultaneous replacement of both organs is increasing. METHODS: Six HNTX recipients, three of them suffering from long-standing type I diabetes, received transplants between September 1990 and March 1996 and were analyzed in terms of clinical and immunological demographics and outcome. They were compared with 379 HTX and 769 NTX recipients operated upon within this period. RESULTS: Survival for HNTX is 100% with a mean follow-up of 32.7+/-21.1 months. Cold ischemic time of the kidney was significantly shorter for HNTX than for NTX (6.5+/-1.0 hr vs. 22.1+/-6.8 hr, P<0.005). Although HNTX patients received HLA-unmatched grafts, no rejection of the kidney has been observed to date. There was no difference for rejection of the heart in HNTX compared to HTX recipients. CONCLUSIONS: Satisfying results are obtained by HNTX and justify the use of two organs for one recipient. The favorable immunological behavior of the kidney despite use of HLA-unmatched grafts is most probably explained by higher immunosuppression and short cold ischemic time, although a combination effect cannot be excluded.

Adult↗
PubMed1997

The differential ability of IL-8 and neutrophil-activating peptide-2 to induce attenuation of chemotaxis is mediated by their divergent capabilities to phosphorylate CXCR2 (IL-8 receptor B).

IL-8 and neutrophil-activating peptide-2 (NAP-2) are two closely related C-X-C chemokines that differ in their abilities to induce chemotaxis of human polymorphonuclear leukocytes (PMN). Although two IL-8R types are expressed by PMN, only CXCR2 binds NAP-2 and IL-8 with equally high affinity. By using enriched CXCR2-transfected 293 cells, we show that high doses of IL-8 induce attenuation of chemotaxis, while equivalent doses of NAP-2 do not. Phosphorylation analysis shows that IL-8 induces higher levels of phosphorylation of the carboxyl terminus of CXCR2 than does NAP-2, suggesting that the level of phosphorylation contributes to the ability of the chemokines to attenuate the chemotactic response. To directly evaluate this difference, we analyzed the ability of receptors mutated to delete regions that highly express potential phosphorylation sites to be phosphorylated and to mediate chemotactic attenuation. We found that a carboxyl terminus-truncated mutant of CXCR2 was not phosphorylated by high doses of IL-8, as determined by in vivo phosphorylation assays and by analysis of the electrophoretic mobility of the receptors on SDS-PAGE gels. This mutated receptor had a significantly lower ability to attenuate IL-8-induced chemotaxis, indicating that the attenuation of chemotaxis is mediated by chemokine-induced receptor phosphorylation. In conclusion, the data show that the greater ability of IL-8 to induce receptor phosphorylation contributes to its more potent attenuation of chemotaxis as compared with NAP-2. This differential phosphorylation by IL-8 and NAP-2 of CXCR2 provides a basis for the divergent outcome of PMN-induced inflammation in response to these two closely related C-X-C chemokines.

Cells, Cultured↗
PubMed1997

Postimport methylation of the small subunit of ribulose-1,5-bisphosphate carboxylase in chloroplasts.

Electron impact mass spectronomy analysis of the amino-terminal amino acid of the small subunit (SSU) of ribulose-1,5-bisphosphate carboxylase (Rubisco) showed that the amino-terminal methionine residue is post-translationally modified to N-methyl-methionine. Modification of the amino-terminal methionine residue was found in mature SSU proteins from the dicotyledonous plants pea and spinach as well as the monocotyledonous plants barley and corn. SSU methyltransferase is a soluble protein in the chloroplast stroma and accepts heterologously expressed non-methylated SSU as a substrate using S-adenosylmethionine as methyl-group donor. We show that this modification occurs after post-translational uptake of the precursor form of SSU into chloroplasts and processing to its mature size. This reaction represents a new step in the import and assembly pathway of Rubisco holoenzyme.

Chloroplasts↗
PubMed1997

Prostaglandin E1--bridge to cardiac transplantation. Technique, dosage, results.

BACKGROUND: Heart transplantation candidates who remain severely symptomatic despite therapy are normally hospitalized. Continuous infusion of intravenous drugs from a portable pump may allow such patients to live a fairly active life until a donor heart is found. AIM: To investigate in an open pilot study if heart transplantation can be safely accomplished if these patients are continuously bridged with various regimens including inotropic support with low-dose dobutamine in conjunction with dopamine and prostaglandin E1. METHODS: We report on 5 years' experience with prostaglandin E1, a potent vasodilator with proven efficacy in severe heart failure when coupled with catecholamines. From 1990 to 1995 54 heart transplantation candidates were bridged with prostaglandin E1 in addition to dobutamine 5 micrograms.kg-1. min-1 and dopamine 3 micrograms.kg-1 min-1 (group A; n = 32) or in addition to 3 micrograms.kg-1 min-1 dopamine alone (group B; n = 22), and 11 heart transplantation candidates were bridged with dobutamine 5 micrograms.kg-1. min-1 and dopamine 3 micrograms.kg-1 min-1 only (group C; n = 11). In an initial dose-ranging test, prostaglandin E1 was uptitrated to side effect limit (29 +/- 1 ng.kg-1.min-1). Haemodynamics, except for stroke volume index, were similar in all patients at baseline and a sufficient haemodynamic response (20% increase in stroke volume) was observed during the acute study. Fifty percent of the peak dose was used for initiating chronic therapy; the dose of prostaglandin E1 was further reduced if side effects recurred. RESULTS: Twenty-nine (54%) patients in groups A and B and six in group C could be discharged home with chronic therapy via a Hickman catheter connected to a portable pump. After 4 weeks in six patients in group A and in 13 patients in group B, when prostaglandin E1 had been reduced from 15 +/- 2 ng.kg-1.min-1 to 8 +/- 1 ng.kg-1 min-1 increases in cardiac index and decreases in systemic vascular resistance were sustained, and a permanent decrease in pulmonary vascular resistance index was observed in group B. Intravenous therapy was changed in nine patients (3/1/5) because of side effects and worsening heart failure. Prostaglandin E1 was withdrawn in three of these patients because of an increase in serum creatinine (3 mg.100 ml-1), and in one because of noncompliance. In total, there were 17 cardiac deaths (9/6/2), 42 heart transplants (22/14/6) and six (1/2/3) weaned survivors (including one non-cardiac death) in this study. Overall outcome was similar in groups A and B, but distribution after 2 months appeared to be different (P < 0.05) based on more transplantations in group A. CONCLUSION: We concluded that chronic infusions with prostaglandin E1 at reduced dosages is a feasible and safe therapeutic adjunct to bridge end-stage heart failure patients and may yield desirable effects in a subset of patients in the absence of inotropic support by dobutamine.

Alprostadil↗
PubMed1997

Prostaglandin E1 infusion compared with prostacyclin infusion in patients with refractory heart failure: effects on hemodynamics and neurohumoral variables.

Prostaglandin E1 or prostacyclin were randomly infused in 18 patients with severe chronic heart failure who did not respond to oral treatment. Maximally tolerated dosages of both agents increased cardiac index; however, only prostacyclin decreased mean arterial pressure and increased plasma norepinephrine significantly. Twelve hours after 50% peak dose reduction, atrial natriuretic peptide levels, right atrial pressure, mean pulmonary artery pressure, and mean arterial pressure continued to decrease with prostaglandin E1, whereas the increase in cardiac index was sustained; in contrast, at 50% prostacyclin dose reduction, cardiac index decreased toward baseline, suggesting that, with reduced dosages for chronic infusions, desired hemodynamic changes seem to be sustained with prostaglandin E1 only.

Alprostadil↗
PubMed1996

Cyclosporine may affect improvement of cognitive brain function after successful cardiac transplantation.

BACKGROUND: The effects of cardiac transplantation on cognitive brain function are uncertain. METHODS AND RESULTS: We measured cognitive brain function and quality of life in out-of-hospital cardiac transplant candidates (n = 55; ejection fraction, 19.9%; age, 54.8 years [means]). After transplantation, the patients were serially reevaluated at 4 months (n = 25) and at 12 months (n = 19). Brain function was measured objectively by cognitive P300 evoked potentials. Additionally, standard psychometric tests (Trail Making Test A, Mini-Mental State Examination, and Profile of Mood State test) were performed. Cognitive P300 evoked potentials were impaired in cardiac transplant candidates (359 ms, recorded at vertex) compared with 55 age- and sex-matched healthy subjects (345 ms, P < .01). Trail Making Test A was also abnormal (45 versus 31 seconds in 55 healthy subjects, P < .01). After transplantation, P300 measures were normalized at 4 months (345 ms, P < .05 versus before transplantation) but declined again at 12 months (352 ms, P = NS versus before transplantation). Stepwise multiple regression analysis revealed that cumulative cyclosporine dosage was the only predictor of individual cognitive brain function 4 months (753 mg/kg body wt, P < .05) and 12 months (2006 mg/kg body wt, P < .01) after transplantation, respectively. CONCLUSIONS: Objective cognitive P300 auditory evoked potential measurements indicate that cognitive brain function is significantly impaired in patients suffering from stable end-stage heart failure. Successful cardiac transplantation is effective to fully normalize impaired brain function. Subsequent relative long-term decline of cognitive brain function after successful cardiac transplantation is strongly suggested to be related to cumulative cyclosporine neurotoxicity.

Affect↗
PubMed1996

Decrease in pacemaker incidence after orthotopic heart transplantation.

A decrease in sinus node dysfunction and pacemaker requirement after orthotopic heart transplantation was observed over a 6.5-year period, probably indicating the effect of a learning curve. Indirect evidence suggests a traumatic genesis of sinus node dysfunction after cardiac transplantation.

Arrhythmia, Sinus↗
PubMed1996

Nutritional status, ICU duration and ICU mortality in lung transplant recipients.

OBJECTIVE: To determine the relation of malnutrition and underlying diagnosis to the length of stay in the Intensive Care Unit (ICU) and to mortality after lung transplantation (LTX). DESIGN: Retrospective ICU chart review. SETTING: Cardiothoracic ICU in a University hospital. PATIENTS: Fifty-one consecutive patients who suffered from end-stage lung disease from April 1992 to January 1994. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The median time spent in the ICU was 5 days (range, 2-123 days). Patients with an underlying diagnosis of obstructive lung disease had significantly shorter ICU stays (median 4 days; range, 2-28 days) than those with restrictive lung disease (median 7 days; range, 2-123 days) (p = 0.005) or pulmonary hypertension (median 10 days' range, 2-38 days) (p = 0.041). Significant differences in ICU duration were observed between patients after double lung transplantation (median 10 days; range, 2-123 days) and those after single lung transplantation (median 4 days; range, 2-36 days) (p = 0.004). No statistically significant difference in ICU duration was found between patients with different nutritional statuses. In those patients who could not be discharged from the ICU before the 5th day, a body mass index (BMI) below the 25th percentile was a statistically significant risk factor for ICU mortality (p = 0.05). CONCLUSIONS: We conclude that the type of transplant procedure and the underlying diagnosis are important predictive indicators of ICU duration. A poor nutritional status (BMI below the 25th percentile) is a risk factor for ICU mortality in cases of patients who stay for 5 days or longer in the ICU.

Adolescent↗
PubMed1996

Impact of glutaraldehyde on calcification of pericardial bioprosthetic heart valve material.

BACKGROUND: This study was conducted to investigate the impact of the preservation method of bioprosthetic heart valve materials on calcification rates and biocompatibility of the biologic tissue. METHODS: In subcutaneous rat implants, conventionally preserved bioprosthetic heart valve material was compared with bovine pericardium that was treated with L-glutamic acid to reduce residual glutaraldehyde released from the fixed tissue. Both these methods were compared with bovine pericardium that was stabilized by a dye-mediated photooxidation reaction without glutaraldehyde. Biocompatibility of these biomaterials was tested in vitro using human endothelial cell cultures. RESULTS: Conventionally preserved bovine pericardium with a high amount of glutaraldehyde incorporated into the tissue resulted in severe calcification 63 days after subcutaneous implantation in rats (165.4 +/- 20 mg Ca2+/g dry weight). Postfixation treatment with L-glutamic acid, which reduces free, unbound aldehyde groups, showed a significant decrease in calcification (89.6 +/- 14 mg Ca2+/g dry weight). Glutaraldehyde-free preservation by dye-mediated photooxidation showed no calcification after 63 days of subcutaneous implantation (1.0 +/- 0.4 mg Ca2+/g dry weight). Regular endothelial cell proliferation was observed on photooxidized and L-glutamic acid-treated tissue, whereas conventionally treated tissue caused endothelial cell death. CONCLUSIONS: This study underlines the detrimental role of glutaraldehyde in the calcification process of bioprosthetic heart valve materials and emphasizes alternative preservation methods that reduce or avoid the use of glutaraldehyde.

Animals↗
PubMed1996

Acceptance of a pump-driven infusion therapy with prostaglandin E1 as a bridge to heart transplantation.

Ambulatory pump-driven intravenous infusions are a novel and - compared with hospitalization-cost-effective procedure to bridge refractory heart failure patients to cardiac transplantation. In the present study 13 patients received chronic infusions with prostaglandin E1 alone or in conjunction with catecholamines and the acceptance of this bridging therapy was investigated over a period of seven weeks. Prostaglandin E1 was uptitrated from 2.5 ng/kg/min to a maximum of 40 ng/kg/min, according to individual tolerance. 50% of the maximum tolerated dose of prostaglandin E1 was used for chronic infusion with a further dose reduction if side effects occurred. Altogether 8 patients who completed the therapy were analysed; of the remaining 5 three patients had a heart transplant, one patient died and one patient did not comply with the protocol. The drugs were administered by an automatic portable pump, which was connected to a subcutaneous tunneled catheter. During hospitalization patients and their relatives were instructed how to prepare drug solutions and to handle the infusion system. Patients' perceptions were investigated by visual analog scale questionnaires (rating scale zero to ten) before, and at weekly intervals during bridging therapy. Initial acceptance was documented as belief in therapy (9.4 +/- 1.2 SD), absence of fear of handling the pump (8.9 +/- 1.2 SD) and confidence of receiving help of close relatives (8.7 +/- 1.8 SD). During the observation period there were no statistically significant differences compared with this favorable starting position and no significant disruption of life style occurred. Pain in the joints-a prostaglandin E1-associated side effect-increased significantly (p < 0.05) at week 5, but returned to baseline levels during the following two weeks. At study end patients confirmed that they would repeat the experience (7.6 +/- 1.4 SD) and advise other patients to undergo this form of therapy (8.2 +/- 1.9 SD). Thus, this pilot study suggests that ambulatory pump-driven intravenous infusion therapy comprising prostaglandin E1 and catecholamines is acceptable to patients as a bridge to heart transplantation and that there should be no major difficulties regarding compliance.

Adult↗
PubMed1995

Measuring extracellular matrix turnover in the serum of patients with idiopathic or ischemic dilated cardiomyopathy and impact on diagnosis and prognosis.

Circulating levels of extracellular matrix components were measured by radioimmunoassays and tested if they were useful for clinical staging in chronic heart failure. In 41 patients with dilated cardiomyopathy (33 idiopathic and 8 ischemic cases), the serum concentrations of procollagen type III aminoterminal peptide (PIIINP), type I collagen telopeptide (ICTP), and basement membrane laminin were significantly higher than in 30 healthy controls regardless of the underlying etiology. Patients with serum values of PIIINP, ICTP, and laminin > 7 micrograms/L, 7.6 micrograms/L, and 2.3 U/ml, respectively, were at higher relative risk for advanced clinical stage, poor hemodynamic condition, hyponatremia, heart transplantation, and death during follow-up than patients with low levels, with the exception that serum laminin > 2.3 U/ml was not significantly associated with hyponatremia and heart transplantation. Despite their interdependence on liver function, circulating levels of PIIINP and ICTP were independent predictors of mortality. In 17 of the 41 patients with cardiomyopathy whose explanted hearts were available for histologic evaluation, serum PIIINP, ICTP, and laminin significantly correlated with the myocardial area fractions of their tissue analogues (PIIINP vs myocardial collagen type III, r = 0.784, p = 0.0013; serum ICTP vs myocardial collagen type I, r = 0.603, p = 0.0527; and serum laminin vs myocardial laminin, r = 0.605, p = 0.0411). In conclusion, the increase in extracellular matrix turnover, which may partially be derived from fibrosis in the myocardium, can be measured in the serum of patients with dilated cardiomyopathy, and has an impact on risk stratification and prognosis.

Cardiomyopathy, Dilated↗
PubMed1995

ICD therapy in survivors of sudden cardiac death awaiting heart transplantation.

The impact of implantable cardioverter defibrillator (ICD) therapy on survival of heart transplant candidates is of major socioeconomic and ethical interest. However, efficacy is even uncertain for patients at highest risk of tachyarrhythmic death on the waiting list. We studied 60 selected heart transplant candidates (mean age, 55.8 years; mean left ventricular ejection fraction, 0.15; functional class III and IV) with a history of successful resuscitation by external electric defibrillation for spontaneous, syncopal ventricular tachyarrhythmia during the study period from March 1992 through September 1994. At the time of registration for transplantation, 30 patients had ICD devices implanted, whereas 30 patients lacked ICD therapy for various nonmedical reasons. Both therapy groups were comparable in clinical and hemodynamic characteristics as well as in intention to transplant (median waiting time to transplantation, 5.7 and 6 months, respectively; not significant by log-rank method). Survival on the waiting list was significantly improved by ICD therapy; only 1 of the 30 ICD patients (19 transplanted) but 7 of the 30 non-ICD patients (14 transplanted) died on the waiting list (p < 0.05 by log-rank method). Implantable cardioverter defibrillator therapy did not affect survival after transplantation as compared with non-ICD patients (not significant by log-rank method). During the waiting time, 26 of the ICD patients (87%) experienced adequate ICD discharges, and 12 of the non-ICD patients were treated successfully by external electric defibrillation (40%).(ABSTRACT TRUNCATED AT 250 WORDS)

Death, Sudden, Cardiac↗