Chronic anemia after lung transplantation: treatment with human recombinant erythropoietin.
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Adult↗
Biomedical subjects
M Grimm
Publications and source records attributed to M Grimm.
Therapeutic whole-blood levels of cyclosporin A in heart and lung transplantation.
The use of cyclosporin A (CyA) as an immunosuppressive drug is limited because of its serious side effects. In order to minimise these toxic side effects while utilising immunosuppressive properties of CyA, the dosage of CyA is generally administered on the basis of the individual CyA whole blood level. Therefore, a frequent determination of CyA whole blood levels is necessary. The aim of our study was to establish therapeutic whole blood levels for patients after heart (HTX) and lung (LuTX) transplantation depending on the interval of time after transplantation. CyA levels were determined by HPLC and by fluorescence polarisation immunoassay (FPIA) with a monoclonal and a polyclonal antibody. Two hundred and ninety-five patients after HTX and 48 patients after LuTX were investigated and patients with rejection and/or pathological kidney and liver function were excluded. No significant differences between the two groups of patients were detected. Therefore, common therapeutic ranges for CyA can be used for adequate immunosuppression for patients after HTX and LuTX.
Antibodies, Monoclonal↗
Failure mode of a new pericardial valve prosthesis (Sorin Pericarbon). A morphological study.
Between February 1986 and February 1992, 144 patients (mean age 69 years) received 149 bovine pericardial valve bioprostheses (Sorin Pericarbon). Out of this group 10 patients required reoperation because of valvular dysfunction. Defect bioprostheses (7 aortic valves, 3 mitral valves), removed 34 to 81 months after implantation, were studied by X-ray analysis as well as light and electron microscopy. Seven out of ten valves were explanted because of valvular stenosis, two valves had to be replaced because of valvular regurgitation and one because of paravalvular leakage. X-ray analysis revealed severe clacification of the cusps in all cases. Mineralization occurred predominantly next to commissural attachment zones. Cuspal tearing, associated with calcific degeneration of the tissue, was observed in two cases. Beside the commissures, accelerated tissue degeneration could be detected near the basal suture line: disintegration of collagen bundles by invading macrophages and mineral deposits was prominent in these regions. Scanning electron microscopy revealed the presence of circumscribed areas of endothelial-like cell lining on both surfaces of the cusps of five explants. Valvular stenosis, caused by severe calcification of commissural as well as basal regions of the leaflets, is the principal failure mode of the Sorin Pericarbon heart valve prostheses. As an additional aspect, the basal suture line must be assumed to be a critical determinant in accelerating tissue degeneration. Long-term clinical studies will be required to evaluate the clinical performance of this valve, focusing on thromboembolic complications, hemodynamic function and long-term durability.
Aged↗
Changes following in vitro endothelial cell lining of ePTFE prostheses: late morphologic evaluation of six failed grafts.
This paper describes the morphologic appearance during long term follow-up of in vitro endothelialised ePTFE grafts (IVECL) implanted in patients with crural reocclusions. Between June 1989 and December 1990, 13 femorocrural IVECL bypasses were implanted. Follow-up angiograms demonstrated stenoses in the middle of the graft in six patients. Two of these patients developed symptoms, and the grafts were biopsied approximately 1.5 years after implantation during a patchplasty procedure. The remaining four patients with asymptomatic stenoses refused elective reoperation and suffered a graft occlusion 53 to 619 days after implantation, all leading to amputation. Biopsy specimens and explanted grafts were examined with standard and electron microscopy. Both biopsies demonstrated multiple layers of degenerating myofibroblasts (MFB). The four explanted grafts also showed altered MFB in addition to necrosis of the graft surface. No endothelial cells were seen on any of the preparations. Long term follow up of IVECL protheses in the crural position has demonstrated that it is possible to lastingly bind cells on an artificial surface. Whether the MFB found are a substitute of lost endothelial cells, or are an end product of metaplastic and/or degenerative alterations, can only be clarified through further biopsy studies.
Arterial Occlusive Diseases↗
Sinus node dysfunction after orthotopic heart transplantation: the Vienna experience 1987-1993.
In the present study, the annual incidence of postoperative sinus node dysfunction and the type of sinus node abnormality after cardiac transplantation were followed over a 6 1/2-year period in 185 patients. Each year the sinus node function was systematically characterized by rhythm and corrected sinus node recovery time in a significant number of patients. Over the entire study period, there were 131 patients with normal sinus node function (corrected sinus node recovery time 318 +/- 55 msec) while 54 patients had latent (n = 24, sinus rhythm, corrected sinus node recovery time 8,053 +/- 2,198 msec) or manifest (n = 30, absence of sinus rhythm or pacemaker dependence) sinus node dysfunction. Twenty-nine patients had pacemaker placement. The incidence of sinus node dysfunction declined in absolute terms and when indexed by the actual number of patients transplanted per year (index 1987: 38.5; 1998: 17.6; 1989: 23.2; 1990: 29.1; 1991: 10.4; 1992: 7.5; 1993: 2.2). Among those with sinus node dysfunction, the annual percentage of patients presenting with prolonged recovery time, escape rhythm, and those reverting back to sinus rhythm until discharge did not change significantly over the study period (P = 0.22). On multivariate analysis, only the date of transplantation was significantly associated with the occurrence of postoperative sinus node deficiency (P = 0.0007) while age of recipient (P = 0.85) or donor (P = 0.96), the type of cardioplegia used (P = 0.09) and ischemic time (P = 0.09) were insignificant.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Thoracoabdominal aneurysm repair: spinal cord protection using profound hypothermia and circulatory arrest.
Between January 1991 and February 1993, 14 patients (11 male, 3 female) between 21 and 79 years of age (median 50 years) underwent reconstruction of the thoracic (n = 7) and thoracoabdominal aorta (n = 7). Four patients had previously undergone operation of the ascending aorta, and in three patients coronary artery bypass grafting had previously been performed. All patients were operated on a via a posterolateral thoracotomy using cardiopulmonary bypass with continuous blood cardioplegia and hypothermic circulatory arrest (11 degrees C nasopharyngeal temperature, flat-EEG). All patent lower intercostal and lumbar arteries (T3 to L5) were reimplanted. The 30-day mortality after repair of the thoracic aorta was 0%; after replacement of the thoracoabdominal aorta, mortality was 28.5% (n = 2). One patient died 70 days after replacement of the thoracic aorta as a consequence of a perioperative stroke. None of the surviving 11 patients developed a permanent neurological deficit or renal or cardiac dysfunction. The average intensive care stay was 6 days for patients after replacement of the thoracic aorta and 18 days for patients after replacement of the thoracoabdominal aorta. Our results suggest that use of elective hypothermia and circulatory arrest for spinal cord protection is highly effective. We, therefore, recommend this method for complex reconstructions of the thoracoabdominal aorta.
Adult↗
Effect of lung transplantation on right and left ventricular volumes and function measured by magnetic resonance imaging.
To evaluate the effect of lung transplantation on right ventricular (RV) and left ventricular (LV) volumes and function, magnetic resonance imaging (MRI) was performed in 11 patients before and 6 to 24 months after single (n = 7) or double (n = 4) lung transplantation as well as in 15 healthy control subjects. Prior to transplantation, RV end-diastolic (RVEDVI, ml/m2) and end-systolic (RVESVI, ml/m2) volume indices were significantly increased in patients compared with those in control subjects. RV ejection fraction (RVEF, %), although within the lower normal range, was significantly reduced. In contrast, LV volume indices (ml/m2) were significantly smaller in patients than in control subjects, whereas LV ejection fraction (LVEF, %) was not different from that in normal subjects. After lung transplantation, MRI revealed a significant reduction in RVEDVI from 73 +/- 29 to 54 +/- 14 (p = 0.03) and RVESVI from 38 +/- 23 to 20 +/- 6 (p = 0.01) with a concomitant significant increase in RVEF from 48 +/- 14 to 63 +/- 6 (p = 0.01). Consecutively, the LV expanded to normal (LVEDVI from 49 +/- 12 to 65 +/- 14, p = 0.01; LVESVI from 23 +/- 9 to 28 +/- 7, p = 0.05), whereas LVEF remained unchanged (55 +/- 9 versus 56 +/- 8).
Adult↗
[HIV retrospective study of the German Red Cross blood donation service in Germany].
OBJECTIVE: It was tried to retrospectively identify HIV infections in recipients of transfusions from donors who were tested HIV positive at a subsequent donation. These lookback data were traced back to answer the following questions: 1. How many transfusion recipients were infected before the start of the routine HIV testing in 1985? 2. How great is the risk of HIV infections from infected but not yet HIV antibody-positive donors? 3. Furthermore, the transfusion of HIV-infected transfusion recipients was traced back to the involved donor to establish causality. DESIGN: Retrospective ('lookback') study. SETTING: HIV Study Group of the Red Cross Blood Banks of the Federal Republic of Germany. PARTICIPANTS: Preceding donations of HIV antibody-positive repeat donors were traced back to the transfusion recipients in order to establish their HIV antibody status. In a second lookback study, HIV-infected transfusion recipients and their corresponding donors were investigated after they had been reported to the blood bank as infected by transfusion-associated HIV. INTERVENTIONS: None. RESULTS: Recipients of 156 respectively 133 transfusions from repeat donors found to be Western blot-positive were investigated from 1985 to 1987 and from 1987 to 1992, respectively. About 50% of the recipients had died. About 40% of the recipients could not be examined, because they either were not available for testing or refused to be tested or because it was impossible to clarify the fate of the blood products. 25 HIV recipients were identified from 1981 to 1985, when routine HIV testing began. Nine transfusion-associated HIV infections were identified from 1985 to 1992. 25 million units of blood were prepared during this period. CONCLUSIONS: The risk of HIV transmission by tested transfusions is extremely rare (in the order of 1:1 million). The second lookback study suggests that in more than 50% of the blood recipients in whom HIV infection was attributed to transfusion, a causal relationship to an infected donor could not be established.
AIDS Serodiagnosis↗
[Cytomegalovirus infection following lung transplantation].
The significance of cytomegalovirus (CMV) infection after lung transplantation was investigated in 20 patients (ten women and ten men; mean age 46 [21-67] years). Indications for transplantation were emphysema (n = 6), cystic fibrosis (n = 2), primary pulmonary hypertension (n = 2), pulmonary fibrosis (n = 5), obliterating bronchiolitis (n = 2), cystic lung (n = 2) and bronchiectasis (n = 1). Incidence, diagnostic parameters (serology, virus isolation and histology) and efficacy of prophylactic and therapeutic measures were recorded. 16 of the 20 patients developed a CMV infection, which in 12 was clinically significant. CMV pneumonia developed in two patients, proving fatal in one. The infection occurred a median of 47 (17-200) days after the transplantation. Administration of Ganciclovir (5 mg/kg twice daily intravenously) brought about remission of symptoms in all but one of the patients and improved the clinical parameters.--This experience demonstrates that regular monitoring of the patients for possible CMV infection and its early therapy can achieve a low death rate.
Adult↗
Successful lung transplantation in a long-term ventilator-dependent patient.
Ventilator dependence has been postulated to be a major contraindication for successful lung transplantation. We describe the case of a 44-year-old female patient mechanically ventilated for 10 months after adult respiratory distress syndrome. After a program of physical training the patient underwent successful bilateral sequential lung transplantation. Six months postoperatively she is in good physical condition and is able to carry out the activities of normal daily living. We conclude that in selected patients long-term mechanical ventilatory support is not a contraindication for lung transplantation.
Activities of Daily Living↗
Exercise chronotropy in patients with normal and impaired sinus node function after cardiac transplantation.
The chronotropic response during graded, symptom limited exercise was investigated in 32 cardiac transplant recipients a mean of 49 +/- 18 days after transplantation. All patients had systematic evaluation of postoperative donor sinus node (SN) function and the cardioacceleratory response was compared according to the SN function. Twenty-one patients had normal postoperative SN studies (corrected SN recovery time < 520 msec, group I) while the SN function was impaired postoperatively in the remainder (n = 11, group II; corrected SN recovery time 4,149 +/- 6,283 msec in 5 patients, junctional escape rhythm in 6 patients). All patients had regained sinus rhythm at time of the exercise test. Patients in group II had lower basal sinus rates at the beginning of exercise (91.5 +/- 11 vs 101.4 +/- 7 beats/min, P < 0.02). This lower chronotropy was maintained over every incremental step (F rate between groups = 30, P = 0.0001, F rate vs workload = 15, P = 0.0001 by two-way ANOVA) and resulted in a significantly lower heart rate at individual peak exercise (108.3 +/- 20 vs 124.2 +/- 13 beats/min, P < 0.02). A total of 14/16 patients in group I but only 2/16 patients in group II accomplished a peak heart rate > or = 120 beats/min (P = 0.009). The workload achieved did not differ between the groups (107 +/- 29 vs 102 +/- 32 watts, P > 0.5). These data show a lower SN chronotropy during rest and at peak exercise in cardiac transplant recipients with postoperative SN deficiency and apparent normalization of SN function.
Adult↗
Early bacterial infections in lung transplant recipients.
Early bacterial pulmonary infections within 2 weeks after lung transplantation were studied in 29 patients undergoing surgery between December 1989 and May 1992. Suspected pulmonary infections occurred in 11 patients (38 percent). The most common bacterial organisms isolated were Klebsiella pneumoniae (45 percent; 5/11), Pseudomonas aeruginosa (36 percent; 4/11), Escherichia coli (27 percent; 3/11), Staphylococcus aureus (18 percent; 2/11), and Enterobacter cloacae (18 percent; 2/11). The mortality due to infection was 3 percent (1/29) in the early postoperative period. None of the following variables was found to be of prognostic significance: positive donor cultures, ischemic time of the graft, use of cardiopulmonary bypass, number of courses of methylprednisolone for acute rejection, duration of postoperative intubation, and type of surgical procedure. The presence of infection in the early postoperative period did not influence long-term survival. In the absence of prognostic parameters, prompt adjustment of antibiotic therapy to the results of antibiograms remains the most important therapeutic step in the management of infections in the early postoperative period after lung transplantation.
Adult↗
In vitro and in vivo endothelialization of glutaraldehyde treated bovine pericardium.
In an experimental study, endothelial cell seeding on glutaraldehyde-fixed and detoxified bioprosthetic tissue, suitable for valve fabrication, was investigated in vitro. These findings were compared to spontaneous endothelial cell ingrowth on vascular grafts fabricated from the same materials. Special consideration was given to the quality of cell attachment with regards to improved shear stress resistance in the endothelial layer covering the bioprosthetic surface. On glutaraldehyde detoxified bovine pericardium, in vitro endothelial cell seeding resulted in uninhibited cell proliferation, but the cells were loosely bound to the underlying tissue. In vivo, endothelial cells grew spontaneously over the surface of vascular implants in direct contact with the bioprosthetic material. In contrast to standard fixed bovine pericardium, a significant decrease in thrombotic appositions could be observed. Cells exhibited intensive production of extracellular matrix, which renders the method of spontaneous in vivo cell ingrowth as the most promising approach for further research.
Animals↗
Early experience with sequential bilateral lung transplantation.
We performed 20 sequential bilateral lung transplantation in 19 consecutive patients from April 1990 to May 1992. Perioperative mortality was low (2 patients). One-year actuarial survival was 70%. All survivors had normal blood oxygen tension (82 mm Hg, mean) while breathing room air and continuing improvement of pulmonary function. Bronchial dehiscence did not occur. Stents were implanted in 7 patients to control bronchial stenosis. Aggressive treatment of graft rejection has been effective in preventing obliterative bronchiolitis.
Bronchial Diseases↗
Cyclosporine A increases angiotensin-converting enzyme activity in heart transplant patients.
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Amino Acid Sequence↗
Decreased tissue reaction to bioprosthetic heart valve material after L-glutamic acid treatment. A morphological study.
Degenerative alterations of two different glutaraldehyde (GA)-fixed bioprosthetic heart valve materials were investigated in subcutaneous rat implants: Bovine pericardium, prepared according to clinically used bioprosthetic heart valve material (BHV) was compared to alternatively preserved pericardium (APHV), which was fixed in GA and treated with L-glutamic acid. Following 63 days of subcutaneous implantation, calcification of APHV implants was significantly lower as compared to BHV implants (13 +/- 6 versus 158 +/- 18 micrograms Ca/mg dry weight tissue; p less than 0.05). In BHV implants ultrastructural investigations showed nucleation of plate-shaped hydroxyapatite crystals at the surface of collagen fibrils and in remnants of connective tissue cells; no signs of calcification could be detected in APHV implants. The time-course of the inflammatory reaction was determined by quantification of immunohistochemical stained mononuclear host-cells invading the implants. In both preparation groups inflammatory reaction reached maximum 42 days after implantation. However, infiltration rate of inflammatory cells was markedly decreased in APHVs as compared to BHVs (p less than 0.05).
Animals↗
Management of severe bronchial ischemia after bilateral sequential lung transplantation.
A case of severe diffuse bronchial ischemia after bilateral sequential lung transplantation is presented. A combination of initial conservative treatment with silicone stenting and late bilateral retransplantation under stable conditions resulted in good clinical outcome. Factors in decision making and technical aspects of the stenting procedure are discussed.
Adult↗
Epidermal growth factor receptor and transforming growth factor alpha expression in human ovarian carcinomas.
The varying tumorbiological behaviour of ovarian carcinomas probably influences operability, response to chemotherapy, being one of the most relevant prognostic factors. Because it is believed that an activation of the epidermal growth factor/transforming growth factor alpha (EGF/TGF alpha) signal pathway could be involved, we analysed the expression of epidermal growth factor receptor (EGFR) and TGF alpha with molecular-chemical, biochemical and immunohistochemical methods in 42 ovarian carcinomas, 4 ovarian metastasis, 2 other malignant ovarian tumours, and in 25 nonmalignant tissues (ovary, myometrium). No major rearrangements or amplification of the EGFR or TGF alpha genes were found. In non-malignant tissues no strong EGFR or TGF alpha signals were detected. TGF alpha is mainly produced by the tumour cells as shown by immunohistochemistry. Four different high molecular weight forms (20-48 kD) were detected in malignant tissues by western blot analysis.
Blotting, Northern↗