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Biomedical subjects

R Zimmermann

Publications and source records attributed to R Zimmermann.

At least 91 records · Page 5Linked to original sources

Functional disturbances due to structural remodeling in the failing human heart.

In severely hypertrophied hearts structural remodeling occurs continuously and finally leads to heart failure. The remodeling process involves all structural components of the cardiomyocyte and all protein families and it consists of cellular enlargement accompanied by degeneration in addition to the occurrence of fibrosis. Nuclei are increased in size but the nuclear volume/cell volume ratio is reduced. Transcription and translation are downregulated for contractile and sarcomeric skeleton proteins but both are upregulated for cytoskeletal and membrane-associated proteins. The connexin43 content is significantly reduced. Chronic degeneration finally leads to cell death by ubiquitin-related autophagy, and acute ischemic cell death (oncosis) is also observed. Apoptosis seems to be of minor importance. The morphological alterations described here are the structural correlate of the typical clinical characteristics of heart failure in human patients: of reduced contractile function, of increased ventricular stiffness represented by an increased left end-diastolic pressure and of ventricular arrhythmia.

Arrhythmias, Cardiac↗

Compression stockings prophylaxis of emergent varicose veins in pregnancy: a prospective randomised controlled study.

QUESTIONS UNDER STUDY: To determine the efficacy of compression stockings in preventing emergent varicose veins in pregnancy. METHODS: A prospective randomised controlled study in the outpatient department of the University Hospital of Zurich, Switzerland, including women with uncomplicated pregnancies <12 weeks at outset of study. A no-stockings control group (n = 15) was compared with two treatment groups: group 1 (n = 12) wore compression class I stockings (18-21 mm Hg) on the left leg and class II stockings (25-32 mm Hg) on the right; in group 2 (n = 15), the compression classes were reversed. Stockings were worn from study entry to term. Endpoints were emergence and worsening of superficial varicose veins, long saphenous vein reflux at the sapheno-femoral junction, and leg symptoms (pain, discomfort, cramps) during pregnancy. RESULTS: Both classes of compression stockings failed to prevent the emergence of superficial varicose veins. However, long saphenous vein reflux at the sapheno-femoral junction was observed in the third trimester in only 1/27 treated women vs. 4/15 controls (p = 0.047); in addition, more treated women reported improved leg symptoms (7/27 vs. 0/15 controls; p = 0.045). Emergent varicose changes, however, did not differ significantly (7/14 controls vs. 5/12 in group 1 and 8/14 in group 2; 3x3 table, Fisher's exact = 0.94). CONCLUSIONS: Although compression stockings do not prevent the emergence of gestational varicose veins, they significantly decrease the incidence of long saphenous vein reflux at the sapheno-femoral junction and improve leg symptoms. Our results also suggest that superficial varices and deep venous insufficiency may have a different aetiology.

Adult↗

A mobile mass spectrometer for comprehensive on-line analysis of trace and bulk components of complex gas mixtures: parallel application of the laser-based ionization methods VUV single-photon ionization, resonant multiphoton ionization, and laser-induced electron impact ionization.

A newly developed compact and mobile time-of-flight mass spectrometer (TOFMS) for on-line analysis and monitoring of complex gas mixtures is presented. The instrument is designed for a (quasi-)simultaneous application of three ionization techniques that exhibit different ionization selectivities. The highly selective resonance-enhanced multiphoton ionization (REMPI) technique, using 266-nm UV laser pulses, is applied for selective and fragmentationless ionization of aromatic compounds at trace levels (parts-per-billion volume range). Mass spectra obtained using this technique show the chemical signature solely of monocyclic (benzene, phenols, etc.) and polycyclic (naphthalene, phenathrene, indol, etc.) aromatic species. Furthermore, the less selective but still fragmentationless single photon ionization (SPI) technique with 118-nm VUV laser pulses allows the ionization of compounds with an ionization potential below 10.5 eV. Mass spectra obtained using this technique show the profile of most organic compounds (aliphatic and aromatic species, like nonane, acetaldehyde, or pyrrol) and some inorganic compounds (e.g., ammonia, nitrogen monoxide). Finally, the nonselective ionization technique laser-induced electron-impact ionization (LEI) is applied. However, the sensitivity of the LEI technique is adjusted to be fairly low. Thus, the LEI signal in the mass spectra gives information on the inorganic bulk constituents of the sample (i.e., compounds such as water, oxygen, nitrogen, and carbon dioxide). Because the three ionization methods (REMPI, SPI, LEI) exhibit largely different ionization selectivities, the isolated application of each method alone solely provides specific mass spectrometric information about the sample composition. Special techniques have been developed and applied which allow the quasi-parallel use of all three ionization techniques for on-line monitoring purposes. Thus, a comprehensive characterization of complex samples is feasible jointly using the characteristic advantages of the three ionization techniques. Laboratory applications show results on rapid overview characterization of mineral oil-based fuels and coffee headspace. The first reported field applications include timely resolved on-line monitoring results on automobile exhausts and of waste incineration flue gas.

Journal Article↗

Quantum mechanical repulsion of exciton levels in a disordered quantum well.

Spatially resolved photoluminescence spectra of a single quantum well are recorded by near-field spectroscopy. A set of over four hundred spectra displaying sharp emission lines from localized excitons is subject to a statistical analysis of the two-energy autocorrelation function. An accurate comparison with a quantum theory of the exciton center-of-mass motion in a two-dimensional spatially correlated disordered potential reveals clear signatures of quantum mechanical energy level repulsion, giving the spatial and energetic correlations of excitons in disordered quantum systems.

Journal Article↗

No benefit from post-caesarean wound drainage.

AIM OF THE STUDY: A prospective randomized controlled trial to determine the benefit of caesarean wound drainage in 305 low-risk pregnant women. METHODS: Pregnant women at low risk of haemorrhage undergoing caesarean section in the Department of Obstetrics, University Hospital, Zurich, between June 1998 and July 1999 were randomised after informed consent into a no-suction group (n = 154) without post-caesarean wound drainage versus a control group with wound drainage (subfascial and subcutaneous) (n = 151). Outcome measures were perioperative decrease in haemoglobin (Hb), postpartum fever (> 38.5 degrees C for > 2 days), sonographic haematoma and other complications requiring revision, cumulative opiate dose adjusted to body weight, length of hospitalisation and operation time. RESULTS: 305 patients completed the study. Decrease in Hb and the rates of fever, haematoma and revision were similar in both groups. However, cumulative opiate dose was lower in the no-suction group (4.5 +/- 1.8 vs 2.8 +/- 1.4 injections, p = 0.0001), and hospital stay was shorter (6.5 +/- 2.4 vs 7.4 +/- 2.8 days, p = 0.0058), as was operation time (32.7 +/- 11.3 v 36.1 +/- 10.5 min; p = 0.0071). CONCLUSIONS: Routine post-caesarean wound drainage is not only useless but cost-ineffective. In the light of our results, wound drainage may be questioned and should be analysed generally.

Adult↗

Prognostic value of Doppler echocardiographic mitral inflow patterns: implications for risk stratification in patients with chronic congestive heart failure.

OBJECTIVES: This prospective study tested whether transmitral flow patterns add incremental value to peak oxygen consumption (VO2) in determining the prognosis of patients with chronic congestive heart failure (CHF) and systolic dysfunction. BACKGROUND: Peak VO2 is an objective marker of functional capacity and is routinely used as a criterion to identify heart transplant candidates. Diastolic dysfunction limits functional capacity, but its prognostic importance relative to that of peak VO2 is unknown. METHODS: Peak VO2 and mitral inflow velocities were prospectively measured in 311 consecutive patients (mean age 54 years, 84% male) with impaired left ventricular function (ejection fraction <40%; 88 patients with ischemic and 223 with dilated cardiomyopathy) who were evaluated for heart transplant candidacy. RESULTS: During a mean follow-up period of 512 +/- 314 days, 65 patients died and 43 patients underwent heart transplantation. Diastolic filling patterns, peak VO2 and left ventricular end-diastolic diameters were independent predictors of cardiac mortality. In patients with peak VO2 < or = 14 ml/min per kg body weight, the outcome was markedly poorer in the presence of restrictive filling patterns as compared with their absence (two-year survival rate 52% vs. 80%). Similarly, despite peak VO2 levels >14 ml/min per kg, the outcome was less favorable in the presence of restrictive filling patterns (two-year survival rate 80% vs. 94%). A risk-stratification model based on the identified independent noninvasive predictors separated groups into those with high (93%), intermediate (65%) and low (39%) two-year survival rates. CONCLUSIONS: Transmitral flow patterns add incremental value to peak VO2 in determining the prognosis of patients with CHF and impaired systolic function.

Blood Flow Velocity↗

Emission of nonchlorinated and chlorinated aromatics in the flue gas of incineration plants during and after transient disturbances of combustion conditions: delayed emission effects.

The profiles of different products of incomplete combustion (PIC) in the flue gas of a 1 MW pilot combustion facility were investigated under normal steady-state and disturbed combustion conditions. The behavior of emission profiles after disturbed combustion conditions was investigated in order to obtain a better understanding of emission memory effects. Highly time-resolved, quantitative on-line measurements of several aromatic species down to low ppbv or higher pptv concentrations were performed by a mobile resonance-enhanced multiphoton ionization time-of-flight mass spectrometer. Conventional analytical methods (gas chromatography-mass spectrometry and high-performance liquid chromatography) were also applied for measurement of polycyclic aromatic hydrocarbons (PAH) and polychlorinated dibenzo-p-dioxins and -furans (PCDD/F). The sampling point was located in the high-temperature region of the plant at the outlet of the post-combustion chamber at temperatures between 650 and 880 degrees C, prior to any emission reduction devices. The investigation pointed out that after a short phase of disturbed combustion conditions, e.g., due to process changes, transient puffs, or malfunctions, the composition of combustion byproducts in the flue gas can be changed drastically for a very long time ("memory emission" effect). It is suggested that carbonaceous layers, deposited on the inner walls in the high-temperature zone of the plant, might be responsible for the observed memory emission of some PAH species. Drastic changes in the profiles of the PCDD/F homologues were also observed during memory emission conditions. The PAH memory most likely is due to pyrolytic degradation of the carbonaceous layers, while the altered PCDD/F homologue pattern may be mediated by the high catalytic activity of the freshly formed deposit layers. Finally, it should be emphasized that a rich pattern of aromatic species, including PCDD/F, was found in a temperature regime well above the typical temperature window (approximately 300 degrees C) for de novo PCDD/F formation.

Air Pollutants↗

Association of immune complexes and plasma viral load with CD4+ cell depletion, CD8+ DR+ and CD16+ cell counts in HIV+ hemophilia patients. Implications for the immunopathogenesis of HIV-induced CD4+ lymphocyte depletion.

OBJECTIVE: There is evidence that HIV induces CD4+ depletion in part by the formation of immune complexes (IC) that attach to CD4+ blood lymphocytes. In the present study we examined the relationship of IC-coated CD4+ blood cells with retroviral replication in HAART-treated patients. PATIENTS AND METHODS: 52 hemophilia patients were studied from 1997 to 1999. Lymphocyte subsets, IgM, IgG and gp120 on CD4+ blood cells, in vitro responses of lymphocytes to mitogens, plasma neopterin and plasma viral load were measured. RESULTS: Patients with detectable viral replication and without ICs on CD4+ blood lymphocytes had a lower viral load (4100 versus 21000 HIV-1 mRNA copies/ml; P = 0.079) and higher CD4+ cell counts (310/microl versus 161/microl; P = 0.035) than patients with ICs on circulating CD4+ lymphocytes. Among patients with < 80 HIV-1 mRNA copies/ml, IC- individuals had slightly higher CD4+ lymphocyte counts than IC+ patients (384/microl versus 316/microl; n.s.). Further evidence for the clinical relevance of the ICs was obtained when 18 patients who had an undetectable viral load at previous investigations were analyzed. Among patients with a stable undetectable viral load, CD4+ counts increased in 6 of 8 IC- but in none of 2 IC+ individuals. In patients whose viral load increased during the observation period, 5 of 6 IC- but none of 2 IC+ individuals showed higher CD4+ cell counts. Impaired virus killing is suggested by lower CD16+ (35/microl versus 107/microl; P = 0.016), higher CD3+ DR+ (178/microl versus 66/microl; P = 0.006), and higher CD8+ DR+ (142/microl versus 34/microl; P = 0.017) cell counts in IC(-) patients compared to IC- patients without detectable viral load. Strong retroviral replication induced strong T cell dysfunctions. Fewer CD3+ 25+ blood lymphocytes (19/microl versus 47/microl; P = 0.006) and a lower in vitro response of T lymphocytes to the mitogens Con A (RR: 0.3 versus 1.2; P=0.023) and CD3 mab (RR: 0.5 versus 2.4; P = 0.012) was observed in IC+ patients with detectable versus undetectable viral load. CONCLUSION: Our data suggest that ICs on circulating CD4+ blood lymphocytes are primarily associated with CD4+ lymphocyte depletion whereas the plasma viral load is primarily associated with decreased T lymphocyte activation, lower CD16+ counts, and higher CD8+ DR+ lymphocytes which might be the effector cells for virus elimination.

Antigen-Antibody Complex↗

Increased soluble Fas in HIV-infected hemophilia patients with CD4+ and CD8+ cell count increases and viral load and immune complex decreases.

Previous studies interpreted increases of soluble Fas (sFas) in the plasma during disease progression in HIV-infected patients as evidence of increased apoptosis of CD4(+) lymphocytes. We studied whether sFas and sFas ligand (sFasL) plasma levels are associated with CD4(+) and CD8(+) lymphocyte counts, plasma viral load, and IgM, IgG, C3d, and gp120 complexes on circulating CD4(+) blood lymphocytes in long-term surviving HIV-infected hemophilia patients, most of whom were receiving HAART. Twenty-six hemophilia patients who were infected with HIV in the early 1980s were investigated in 1997, 1998, and 1999. HAART was initiated in 1996 and 1997 in most patients. Lymphocyte subpopulations and immune complex-coated CD4(+) lymphocytes in the blood were investigated by flow cytometry, plasma viral load (HIV-1 mRNA copies/ml plasma) was tested with HIV-1 QT Nuclisens kits, sFas (ng/ml) and sFasL (ng/ml) plasma levels were measured with MBL ELISA kits, and the in vitro response of patient lymphocytes was tested in cell cultures. During the period from 1997 to 1999 we observed an increase in sFas plasma levels (p = 0.003) as well as in CD4(+) (p = 0.004) and CD8(+) (p = 0.023) cell counts; a decrease in IgG (p = 0.047), C3d (p = 0.024), and gp120 (p = 0.001)-coated CD4(+) lymphocytes in the blood; and a decrease in the number of impaired mitogen stimulation assays (p = 0.013). sFas was negatively associated with viral burden (r = -0.662, p = 0.0002) as well as with CD4(+)IgM(+) (r = -0.554, p = 0.004), CD4(+)IgG(+) (r = -0.431, p = 0.031), CD4(+)C3d(+) (r = -0.551, p = 0.041), and CD4(+)gp120(+) (r = -0.430, p = 0.041) blood lymphocytes, CD8(+)DR(+) cell counts (r = -0.700, p = 0.016), and impaired in vitro responses of patient lymphocytes to PHA (r = -0.475, p = 0.016). sFasL was negatively associated with total lymphocyte counts (r = -0.433, p = 0.027), as well as with absolute numbers of CD3(+) (r = -0.492, p = 0.011) and CD8(+) (r = -0.432, p = 0.027) cells. We conclude that, contrary to expectations, sFas plasma levels increased in long-term surviving HIV-infected hemophilia patients receiving HAART, concomitant with increases in CD4(+) and CD8(+) cell counts. Increased sFas may reflect the growing pool of T lymphocytes that recovers because of a decreasing viral burden and a decreasing immune complex load of CD4(+) lymphocytes.

Antigen-Antibody Complex↗

Translocation of a human focal adhesion LIM-only protein, FHL2, during myofibrillogenesis and identification of LIM2 as the principal determinants of FHL2 focal adhesion localization.

LIM domain proteins are found to be important regulators in cell growth, cell fate determination, cell differentiation, and remodeling of the cell cytoskeleton. Human Four-and-a-half LIM-only protein 2 (FHL2) is expressed predominantly in human heart and is only slightly expressed in skeletal muscle. Since FHL2 is an abundant protein in human heart, it may play an important role in the regulation of cell differentiation and myofibrillogenesis of heart at defined subcellular compartment. Therefore, we hypothesized that FHL2 act as a multi-functional protein by the specific arrangement of the LIM domains of FHL2 and that one of the LIM domains of FHL2 can function as an anchor and localizes it into a specific subcellular compartment in a cell type specific manner to regulate myofibrillogenesis. From our results, we observed that FHL2 is localized at the focal adhesions of the C2C12, H9C2 myoblast as well as a nonmyogenic cell line, HepG2 cells. Colocalization of vinculin-CFP and FHL2-GFP at focal adhesions was also observed in cell lines. Site-directed mutagenesis, in turn, suggested that the second LIM domain-LIM2 is essential for its specific localization to focal adhesions. Moreover, FHL2 was observed along with F-actin and focal adhesion of C2C12 and H9C2 myotubes. Finally, we believe that FHL2 moves from focal adhesions and then stays at the Z-discs of terminally differentiated heart muscle.

Actins↗

Paired comparison of apheresis platelet function after storage in two containers.

Platelet quality after storage strongly depends on the pre-storage quality as well as on the storage conditions determined by the storage container. In this paired study, we evaluated two different containers (MedSep CLX and Delmed DPL-110). The Fresenius AS104 cell separator was used to prepare 17 platelet concentrates that were split and distributed into the containers to be compared. Cell counts, blood gas analysis, morphological scores, glucose and lactate levels, platelet activation, and platelet aggregation were measured before splitting at the day of preparation and after storage at day 3 and day 5. At day 3, there was no significant difference between the two bags apart from increased lactate and decreased pCO(2) concentrations in the CLX bags. At day 5 there were significantly higher lactate concentrations, pO(2) levels, and aggregation after stimulation in the CLX group, while the glucose and pCO(2) concentrations were significantly lower in these platelet concentrates as compared to the DPL-110 group. However, these parameters did not influence the functional parameters tested. While the platelet quality decreased during storage in all bags, the functional changes were nearly identical in both bags tested. We conclude that both bags are equivalent for 5-day storage of platelet concentrates.

Blood Preservation↗

Storage of single donor platelet concentrates: paired comparison of storage as single or double concentrates.

Modern cell separators allow the collection of two plateletpheresis concentrates (PCs) at one session. This study evaluates the quality of PCs stored as double concentrates in standard storage containers of two manufacturers. We collected 20 PCs that contained 4.5 x 10(11) platelets in 375 ml plasma (10 using the COBE Spectra and 10 using the Fresenius AS.TEC 204 with 500 ml bags) that were split into one unit of 3.0 x 10(11) platelets in 250 ml (3.0-PC) and one of 1.5 x 10(11) platelets in 125 ml (1.5-PC). Storage of one 3.0-PC per bag of a two-bag system corresponded to storage conditions for double PCs and storage of one 1.5-PC per bag to storage conditions of single PCs. Cell counts, blood gas analysis, glucose and lactate levels, platelet aggregation, and activation and plasma levels of beta- thromboglobulin (beta-TG) and complement factor 3a (C3a) were measured before storage and again on days 3 and 5. COBE 3.0-PCs demonstrated less pH rise, lactate production, CD 62P expression and beta-TG plasma levels, and better aggregability after storage than COBE 1.5-PCs. Fresenius 1.5-PCs had similar platelet quality to COBE 3.0-PCs. Fresenius 3.0-PCs showed a fall of pH (day 5: 6.22 +/- 0.56), the highest amount of anaerobic glycolysis compared to all other storage conditions investigated, high CD 62P- expression and beta-TG plasma levels, and impaired aggregability on days 3 and 5. The highest C3a levels were found in COBE 1.5-PCs. 3.0 x 10(11) platelets in 250 ml plasma should be stored either in one bag of the COBE system or in two 500 ml bags of the Fresenius system. The COBE two-bag system allows the storage of two PCs without loss of platelet quality. Two PCs should not be stored in the Fresenius C4L 500 ml storage containers.

Blood Chemical Analysis↗

[40 years to Flegel's disease (hyperkeratosis lenticularis perstans)].

A case report of hyperkeratosis lenticularis perstans (Flegel) is presented. The disease is characterized clinically, histologically and with electron microscope. The evolution of the disease since Flegel described it 40 years ago is considered, with emphasis on etiology, pathogenesis and unanswered questions.

Aged↗

Systolic and diastolic properties and myocardial blood flow in the heterotopically transplanted rat heart during acute cardiac rejection.

The aim of the study was to characterize the course of systolic and diastolic function, myocardial blood flow, and histologic changes during acute rejection in a model of heterotopic transplantation in rats. For this purpose isogenic Lewis-to-Lewis and allogenic DA (Dark Agouti)-to-Lewis rat cardiac transplants were studied 1 hour and 1, 3, and 5 days, respectively, after heterotopic intraabdominal transplantation. Myocardial tissue blood flow (MBF) was assessed by the hydrogen-clearance method. An implanted balloon was used to measure pressure-volume relations in the transplanted heart. Myocardial water content was determined at the end of the experiments, and histologic examinations were performed. The MBF recovered during the first day postoperatively in both groups and decreased again in the allogenic group after 3 and 5 days (p < 0.05); it remained stable in the isogenic group. Myocardial relaxation was already prolonged in the allogenic group after 3 days and deteriorated further. Left ventricular end-diastolic pressure progressively increased in the allogenic group, whereas it remained unchanged in the isogenic group up to 5 days. After recovery from ischemia, the left ventricular peak systolic pressure was stable in the isogenic group for the entire further observation period, but it significantly decreased in the allogenic group after 5 days (p < 0.05). Myocardial water content showed a significant increase in the allogenic group compared to that in the isogenic group after 5 days. In the allogenic group histologic examination confirmed mild to moderate rejection after 3 days and severe acute rejection after 5 days. Thus, after recovery from ischemia, mild to moderate cardiac rejection was associated with reduced MBF and impaired relaxation. In a typical sequence, generation of edema and impaired diastolic compliance were terminally followed by systolic dysfunction during severe rejection.

Animals↗

Prenatal diagnosis of a fetus with lumbar myelocystocele.

We present a case of a fetal lumbar myelocystocele, a rare congenital malformation, characterized by herniation of the central canal through a bony spina bifida. Routine ultrasound examination at 11 weeks' gestation by the primary obstetrician showed a suspicious cyst on the fetal back. Initially, the suspected diagnosis was a meningocele. After sonographic detection of newly developed fetal brain anomalies at 22 weeks' gestation the patient was referred to us. The enlarged cyst, which floated freely in the amniotic fluid, had a funnel-like appearance and was covered by a very thin layer of skin. With the help of ultrafast fetal magnetic resonance imaging the diagnosis of a fetal myelocystocele was made.

Adult↗

Reference values of fetal peak systolic blood flow velocity in the middle cerebral artery at 19-40 weeks of gestation.

OBJECTIVES: The objectives of this prospective study were (i) to establish new reference values of peak systolic blood flow velocity measurement in the fetal middle cerebral artery (MCA-PSV) following validated methodological guidelines and (ii) to develop a method to calculate Z-scores of MCA-PSV. PATIENTS AND METHODS: Cross-sectional data were obtained from 331 pregnant women between 19 and 40 weeks' gestation. Reference ranges for MCA-PSV were constructed and for each measurement linear regression models were fitted separately to the mean and standard deviations (SD) as a function of gestational age. An application to calculate Z-scores was developed. A comparison was made between the reference ranges produced in our study and those of a previous one. RESULTS: A new chart, table of centiles and regression equations of MCA-PSV are presented. Comparison of our reference ranges with ones produced in a previous study showed similar 5th centile values. However, the values for the 50th and 95th centiles between 19 and 28 gestational weeks were lower in our study. CONCLUSIONS: We have constructed reference ranges for MCA-PSV which, because they are derived from a larger number of examinations in the 15-20-week period and because the methodological flaws of the previously published study have been eliminated, we consider to be more accurate and therefore more useful for clinical practice.

Blood Flow Velocity↗

Collection of MNCs with two cell separators for adoptive immunotherapy in patients with stage IV melanoma.

BACKGROUND: MNCs for adoptive immunotherapy may be collected by leukocytapheresis with a cell separator. STUDY DESIGN AND METHODS: Six healthy cytapheresis donors donated two MNC concentrates on a cell separator (AS.TEC 204, Fresenius): one on the standard MNC program and one on a modified MNC program with reduced centrifuge velocity that leads to a lower platelet contamination. Seventeen patients with malignant melanoma donated 26 MNC concentrates: 5 on the AS.TEC 204 MNC program, 9 on the modified AS.TEC 204 MNC program, and 12 on another modified MNC program (Spectra, COBE). RESULTS: In the course of cultivation of MNCs to dendritic cells (DCs), the donor MNC concentrates with the lower platelet contamination (475 +/- 85 x 10(9)/L) had a significantly higher relative DC yield (low platelet contamination: 3.9 +/- 1.6% of the plated cells; high platelet contamination: 2.5 +/- 1.8% of the plated cells; p = 0.019) than the concentrates with the higher platelet contamination (2364 +/- 448 x 10(9)/L). No significant difference was found in the yields of MNCs and CD14+ cells in the three protocols used for the collection of MNCs from patients with melanoma. The components obtained by the standard AS.TEC 204 MNC program had a significantly higher platelet contamination (1768 +/- 994 x 10(9)/L) than the components obtained by the modified AS.TEC MNC program (360 +/- 98 x 10(9)/L; p<0.05) and the modified Spectra MNC program (636 +/- 266 x 10(9)/L); p<0.05). Because of the low number of investigated components, no significant difference in the DC yield of the three protocols could be detected (mean DC yield after cultivation: 746 +/- 429 x 10(6)). CONCLUSION: A high platelet contamination of MNC concentrates intended for adoptive immunotherapy can lead to a significant impairment of the DC yield after cultivation. Both the modified AS.TEC 204 and the modified Spectra MNC programs are well suited for collecting MNC concentrates with high MNC yields and low platelet contamination from patients with malignant melanoma.

Adult↗