Biomedical subjects

H Bartels

Publications and source records attributed to H Bartels.

At least 55 records · Page 3Linked to original sources

PubMed1998

Intensified conditioning regimen in bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia.

We investigated an intensified conditioning regimen including fractionated total body irradiation (12 Gy), etoposide (30-45 mg/kg) and cyclophosphamide (120 mg/kg), followed by autologous (n = 5), allo-related (n = 13) or allo-unrelated (n = 6) bone marrow (n = 22) or peripheral stem cell (n = 2) transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. One patient received busulfan (16 mg/kg) instead of TBI. Nineteen patients were transplanted in 1CR, two in 2CR, one in 1PR and two in relapse. Major toxicity was mucositis grade II according to the Bearman scale in all patients. The treatment-related mortality was 25%, mainly due to infection or GVHD after allogeneic transplantation. After a median follow-up of 45 months (range 2-93), nine patients (37.5%) remain alive in CR. Nine patients (37.5%) relapsed and eight (33.3%) of these subsequently died. After autologous transplantation, four of five patients (80%) relapsed and died. Late relapse was seen after allogeneic, as well as autologous transplantation, at 33 and 59 months, respectively. The Kaplan-Meier estimate of leukemia-free survival for all patients is 38% at 3 years (95% CI: 18-58%) and 35% at 5 years (95% CI: 15-55%). For allogeneic transplants in first CR (n = 15) the estimate of disease-free survival was 46% at 3 years (95% CI: 19-73%) and 34% at 5 years (95% CI: 17-51%). Patients aged below 30 years had a better estimated overall survival at 3 years (61% vs 11%, P < 0.001). The bcr-abl fusion transcript (p210 vs p190 vs p210/190) did not affect disease-free or overall survival. In our experience, an intensified conditioning regimen seems to improve the results of bone marrow transplantation in patients with Ph+ acute lymphoblastic leukemia. However, the high relapse rate warrants novel approaches to enhance anti-leukemic efficacy.

Adolescent↗

PubMed1998

Correlation of cytogenetic, molecular cytogenetic, and clinical findings in 59 patients with ANLL or MDS and abnormalities of the short arm of chromosome 12.

Abnormalities of the short arm of chromosome 12 (12p) are found in about 5% of acute nonlymphocytic leukaemias (ANLL) and myelodysplastic syndromes (MDS). They are described to be characteristic of secondary leukaemias, especially after prior mutagenic exposure, and to be associated with a poor prognosis. In our series of 59 patients with 12p abnormalities and ANLL or MDS, exposure to genotoxic agents was proven only in five patients, but in 13/44 patients ANLL evolved from an MDS. Patients with a small deletion del(12)(p11.2p13) having a mild clinical course were distinguished from those with a large del(12)(p11.2), additional chromosomal anomalies, and a poor clinical course. Among the 31 patients with translocations or dicentric chromosomes involving 12p, a group of eight with t/dic(12;13) was the most frequent and was associated with a poor prognosis. The clinical outcome was adverse in the majority of patients with complex karyotype abnormalities, but in some patients a milder clinical course seems likely. A new, hitherto undescribed, abnormality in an MDS case with a duplication dup(12)(p11.2p13) was the amplification of the signal of the yeast artificial chromosome (YAC) clone 964c10 (D12S736). In 38 cases with deletions or unbalanced translocations/dicentrics one YAC signal was lost. Five patients with balanced translocations demonstrated breakpoints within the YAC, containing the ETV6 (TEL) gene. The breakpoints were telomeric to the YAC 964c10 in seven cases and centromeric in one patient.

Adult↗

PubMed1998

Preoperative risk analysis and postoperative mortality of oesophagectomy for resectable oesophageal cancer.

BACKGROUND: Postoperative mortality after oesophagectomy for oesophageal cancer depends largely on the preoperative physiological status of the patient. METHODS: A composite scoring system to predict the risk of oesophagectomy based on objective preoperative parameters was developed based on a retrospective review of patients operated on and evaluated prospectively in two subsequent patient groups. RESULTS: An initial retrospective multivariate analysis of 432 patients who had oesophagectomy identified a compromised general status (P < 0.001) and poor cardiac (P < 0.001), hepatic (P < 0.05) and respiratory (P < 0.05) function as independent predictors of a fatal postoperative course. Based on the relative risk associated with the individual impaired organ functions, a composite risk score was established. A prospective study in 121 patients confirmed that this composite scoring system provides a better identification of high-risk patients than any of the individual parameters. Inclusion of the composite score into the process of patient selection and choice of the procedure resulted in a decrease of postoperative mortality rate from 9.4 per cent (52 of 553) to 1.6 per cent (four of 252) (P < 0.001). CONCLUSION: The risk of death after oesophagectomy for oesophageal cancer can be assessed objectively before surgery and quantified by a composite risk score. This score provides a useful tool for refining the criteria of patient selection for resection or the choice of procedure.

Esophageal Neoplasms↗

PubMed1998

Studies of persistent infection by Chlamydia trachomatis serovar K in TPA-differentiated U937 cells and the role of IFN-gamma.

Inoculation of phorbol ester-differentiated U937 cells as a model for human macrophages with Chlamydia trachomatis of the urogenital serovar K resulted in a persistent infection, with maximal growth at day 7, until day 10 post-infection. At these times inclusion bodies were present in 0.5-2% of the cells. Typical inclusion bodies containing elementary bodies and reticulate bodies were observed by electron microscopy. Furthermore, single chlamydial particles resembling atypical elementary or intermediate bodies were identified in the cytoplasm in > 80% of the host cells. IFN-gamma exerts antichlamydial activity in epithelial and fibroblastoid cells, but the infection of U937 cells by C. trachomatis was not affected by IFN-gamma. The activity of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) was not detected in untreated or in IFN-gamma-treated or chlamydiae-infected or mock-infected U937 cells. The presence of atypical persisting chlamydiae and the lack of IDO expression in U937 cells indicates that the development of these atypical bacteria is independent from IFN-gamma-mediated tryptophan deprivation and other IFN-gamma-mediated effects. Evaluation of persistently infected cells revealed that the expression of the chlamydial major outer-membrane protein, heat-shock protein (hsp60) and lipopolysaccharide (LPS) antigens was not significantly altered in the course of the culture. An intense staining of the LPS on the surface of the host cells was demonstrated by immunofluorescence. The data show that phorbol ester-differentiated U937 cells restrict chlamydial growth strongly but not completely through a mechanism distinct from IDO-mediated tryptophan deprivation. The mechanisms of persistence of chlamydiae in monocytes, which differ considerably from those described for other cells, require further investigation.

Antigens, Bacterial↗

PubMed1998

[Respiratory burst and phagocytosis activity in patients with infection after surgical abdominal interventions].

Phagocyte functions such as respiratory burst or phagocytic activity allow the determination of septic courses. Already in case of surgical stress a reduced constitutive generation of reactive oxygen metabolites could be shown, which is assumed to influence the outcome of following septic courses. The results of septic patients suggest that in spite of a functioning uptake of particles and germs (phagocytosis) a defect of intracellular killing (respiratory burst) exists.

Abdomen↗

PubMed1998

[Special therapeutic approaches for interrupting the cascade--from systemic inflammatory response syndrome to multiple organ failure].

SIRS, sepsis and MOF are clinical sequelae related to persistent, uncontrolled inflammation. Therefore, different strategies for treatment were designed to block the cascade from SIRS to MOF (anti-inflammatory therapies). However, clinical trials using these agents have failed to demonstrate any benefit. In sepsis the body also mounts an anti-inflammatory response, which has been largely ignored. If the anti-inflammatory reaction is sufficiently severe, we might increase the susceptibility to infection or even exacerbate immunosuppression by using anti-inflammatory agents. In contrast, agents to stimulate the immune system--like IFN-gamma or G-SCF--may prove beneficial.

Adjuvants, Immunologic↗

PubMed1998

[Early extubation vs. late extubation after esophagus resection: a randomized, prospective study].

UNLABELLED: In the present study, so far 131 patients with transmediastinal esophagectomy and 104 patients with transthoracic esophagectomy were investigated concerning clinical results (complication rate/mortality) following early extubation (within 6 h postoperatively) or prolonged ventilation (> 24 h). Age tumor stage and risk profile did not differ between the two patient groups. RESULTS: Following transmediastinal esophagectomy, early extubation is superior concerning "stay in the ICU" (7.1 days vs 12.3 days) and complication rate (13.4% vs 32.8%). In contrast, following transthoracic esophagectomy, hospital lethality increases after early extubation (9.8% vs 1.9%).

Esophagectomy↗

PubMed1998

[Achalasia and carcinoma of the esophagus: incidence, prevalence and prognosis].

Although the prevalence of patients with achalasia developing an esophageal carcinoma is low the risk is nearly 140-fold; there is no difference in prognosis between patients with achalasia-carcinoma and those with esophageal cancer without achalasia. We propose a follow-up with biennial endoscopies after 15-20 years of known achalasia. This is accordance with a recent consensus conference, which accepted the recommendation of the American Society of Gastrointestinal Endoscopy [3]. In doubtful findings we recommend brush cytologies and/or biopsies, especially if there should be a recurrence of "old symptoms" or the appearance of "new difficulties" which suggest the possibility of a malignant growth.

Adolescent↗

PubMed1997

Radical transhiatal esophagectomy with two-field lymphadenectomy and endodissection for distal esophageal adenocarcinoma.

Distal adenocarcinoma of the esophagus is defined as a tumor originating from an endobrachyesophagus or a tumor with its main tumor mass (more than two-thirds) located in the distal tubular esophagus. Controversy exists about the optimal mode of surgical resection. Some favor transthoracic esophagectomy, whereas others prefer transhiatal (blunt) esophagectomy. A radical transhiatal esophagectomy (RTE) combined with two-field lymphadenectomy and mediastinoscopic dissection of the upper thoracic esophagus (endodissection) is described herein. We assessed the short- and long-term results of this technique and compared them to a historical group of patients undergoing conventional transhiatal esophagectomy (THE) for adenocarcinoma of the distal esophagus. Altogether 124 patients underwent transmediastinal esophagectomy because of adenocarcinoma of the distal esophagus in our department between January 1986 and May 1995. Thirteen of these patients were excluded from this analysis because of preoperative chemotherapy. The remaining 109 patients were divided into two groups: 62 patients who underwent THE between January 1986 and March 1991 (51 men, 11 women; mean age 65.3 years, range 31-83 years) and 47 patients who had RTE between April 1991 and May 1995 (44 men, 3 women; mean age 63.4 years, range 41-84 years). To compare the long-term results of RTE and THE, we used a matched-pairs analysis considering tumor stage and age. The hospital (30-day) mortality was marginally lower in the RTE group (4.3% versus 6.4%), resulting in an overall mortality of 5.5%. The rate of pulmonary complications was insignificantly lower in the RTE group [19.1% RTE versus 25.8% THE; not significant (NS), and the rate of postoperative cardiac abnormalities significantly decreased after RTE (2.6% RTE versus 19.3% THE; p < 0.05). The overall rate of R0 resections was 87.2% (82.2% RTE, 87.1% THE). Overall survival was similar within the two study groups. Complete tumor removal, T and N stages, and the lymph node ratio were identified as prognostic factors for long-term survival. Overall survival was better after RTE than after conventional THE in patients with involved lymph nodes. The mean number of resected lymph nodes per patient in the RTE group was 26.7. Positive lymph nodes were most common in the paracardial region and at the lesser curvature (72%/10.8% of all invaded abdominal nodes). In the mediastinum positive nodes were most common in the paraesophageal and paraaortal region (48%/27% of all mediastinal nodes). Patients with positive abdominal and mediastinal lymph nodes had a poor long-term prognosis. Distal adenocarcinoma of the esophagus can be safely resected by RTE with two-field lymphadenectomy and endodissection. This technique allows radical "enbloc" resection of the tumor-bearing distal third of the esophagus, which includes the primary area of lymph node metastasis of adenocarcinoma of the distal esophagus: the lower mediastinum and paracardial region. The analysis showed that RTE incurred fewer cardiac complications and a better overall survival in N1-positive patients when compared retrospectively to THE. Intraoperative mediastinoscopy allows controlled dissection of the upper mediastinum and biopsy of several mediastinal lymph nodes, with the advantage of providing additional staging information.

Adenocarcinoma↗

PubMed1997

[Risk assessment].

The aim of preoperative risk analysis is to reduce postoperative morbidity and mortality by identification of compromised organ function which can be improved by targeted preoperative measures and problem-oriented postoperative therapy. Ideally, therefore, preoperative risk assessment, influences the timing of the surgical procedure, the choice of the surgical approach, and the postoperative management. Identification of preexisting relevant disorders that may influence the postoperative course is an essential prerequisite of risk analysis. While preoperative risk analysis today gains in importance with the increasing extent of elective surgical procedures, preoperative risk evaluation still plays a minor role in the emergency situation when the given patient-dependent risk usually has to be accepted. Objective risk evaluation depends on the general and nutritional status, the pulmonary, cardio-vascular, hepatic, and renal function, and the cooperation of the patient. These factors, however, clearly have to be seen in relation to the type and extent of the planned surgical procedure. The selection of additional tests of organ function, exceeding the standard tests required prior to any surgical intervention, must be guided by the extent of the planned surgical procedure, the physiologic alterations associated with the surgical procedure, and the suspected underlying organ dysfunction. Generally accepted multi-factorial classification systems to identify patients at risk for a wide spectrum of surgical procedures are currently not available. Using the model of esophagectomy in patients with esophageal cancer we could, however, demonstrate that a quantitative assessment of the peri- and postoperative risk based on preoperatively available physiologic parameters is possible and markedly reduces postoperative mortality when applied prospectively. The development and validation of similar risk-score systems for other surgical procedures should be considered.

Chronic Disease↗

PubMed1997

Expression of the gap junction protein connexin43 in the subependymal layer and the rostral migratory stream of the mouse: evidence for an inverse correlation between intensity of connexin43 expression and cell proliferation activity.

Connexins constitute the channel-forming proteins of gap junctions. Gap junctions are considered to be involved in the regulation of cell proliferation. To verify this hypothesis for connexin43, the most abundant connexin in brain tissue, we have analyzed the expression of this gap junction protein in the subependymal layer and the rostral migratory stream of the murine telencephalon. These regions reveal high proliferative activity, even during postnatal stages and in adulthood. Proliferating cells were labeled in vivo by means of the bromodeoxyuridine method and were later processed for double immunocytochemistry by using an antibody to connexin43. The relationship between connexin43 expression and cell proliferation was also determined in primary cell cultures of olfactory bulbs from newborn mice. The intercellular coupling efficiency of cultured bulbar cells was also analyzed by dye-transfer experiments in combination with the bromodeoxyuridine technique. In the rostral migratory stream, connexin43 was upregulated during postnatal development, coinciding with a decrease of BrdU incorporation. Comparative quantification of the intensity of connexin43 immunoreactivity by confocal laser microscopy and of BrdU-labeled cells showed a clear reverse correlation between connexin43 expression and cell proliferation in the rostral migratory stream during postnatal development. A marked reverse correlation of both parameters was also observed in primary cell cultures from olfactory bulbs at day 6 after seeding.

Animals↗

PubMed1997

Sequential high-dose therapy and autologous stem cell transplantation for treatment of mantle cell lymphoma.

BACKGROUND: Mantle cell lymphoma (MC) is not curable with conventional chemotherapy. To improve the prognosis of patients with this disease, we prospectively studied an intensive sequential therapy consisting of the Dexa-BEAM regimen (dexamethasone, BCNU, etoposide, ara-C, melphalan) followed by myeloablative therapy with autologous stem cell reinfusion. PATIENTS AND METHODS: Nine consecutive patients with stage III/IV MC were included. Two had untreated disease, four were in first remission, whereas three had more advanced disease. All patients underwent one to two cycles of Dexa-BEAM chemotherapy to reduce the tumor load and to mobilize peripheral blood progenitor cells (PBPC). Subsequently, patients were treated with high-dose radiochemotherapy followed by PBPC reinfusion and were prospectively analyzed for residual disease by clinical methods as well as by PCR amplification clonal CDRIII rearrangements. RESULTS: With an overall response rate of 100%, the initial Dexa-BEAM cycles effectively reduced the tumor load. All patients proceeded to high-dose therapy and subsequent stem cell rescue. Engraftment was prompt, and procedure-related deaths did not occur. With a median follow-up of 12 (3-33) months post transplant, all patients are alive in continuing clinical and molecular remission. CONCLUSIONS: Sequential intensive therapy consisting of Dexa-BEAM and high-dose radiochemotherapy appears to be a highly effective treatment for patients with MC. However, the data are still preliminary, and larger patient numbers and a longer follow-up are required.

Adolescent↗

PubMed1997

Boerhaave's syndrome: analysis of the literature and report of 18 new cases.

Postemetic spontaneous rupture of the esophagus is an intrathoracic disaster which is generally lethal if untreated. The tragedy seems to strike more often than commonly suspected. The current literature review focuses on publications since 1980 and includes the retrospective review of 18 additional patients treated in our hospital for spontaneous rupture of the esophagus. Frequently, a wide variety of unspecific symptoms has led to the mistaken diagnosis of an acute abdomen, pancreatitis or cardiac arrest. About 40% of the patients with spontaneous rupture of the esophagus presented a history of alcoholism or heavy drinking and 41% suffered from gastroduodenal ulcer disease. Pain (83%) and vomiting (79%) often associated with dyspnea (39%) and shock (32%) are the major symptoms. This unspecific symptomatology delayed the correct diagnosis of the Boerhaave's syndrome and resulted in a significant complication rate. The mortality rate associated with Boerhaave's syndrome was 50% from the first successful surgical repair in 1947 by Barrett to 1980. After 1980, however, the mortality rate dropped to 31%, because of earlier diagnosis, surgical repair and improvement in intensive care. When surgery is delayed, the prognosis of patients with spontaneous rupture of the esophagus is in general severe.

Abdomen, Acute↗

PubMed1997

Distinct mechanisms of immunosuppression as a consequence of major surgery.

Altered host defense mechanisms after major surgery or trauma are considered important for the development of infectious complications and sepsis. In the present study, we demonstrate that major surgery results in a severe defect of T-lymphocyte proliferation and cytokine secretion in response to coligation of the antigen receptor complex and CD28. During the early postoperative course, reduced cytokine secretion was observed for interleukin-2 (IL-2), gamma interferon, and tumor necrosis factor alpha, which are associated with the Th1 phenotype of helper T lymphocytes, and for IL-4, the index cytokine of Th2 cells. During the late postoperative course, T-cell cytokine secretion increased to normal levels. Production of the anti-inflammatory cytokine IL-10 was altered, with different kinetics being selectively elevated during the late postoperative course. In contrast, the capacity of peripheral blood monocytes to present bacterial superantigens and to stimulate T-cell proliferation was normal or enhanced after surgery despite a significant loss of cell surface HLA-DR molecules. Thus, the level of major histocompatibility complex class II protein expression does not appear to predict the antigen-presenting capacity of monocytes obtained from surgical patients with uneventful postoperative recovery. Secretion of IL-1beta and IL-10 by endotoxin-stimulated peripheral blood monocytes was increased at different time points after surgery. Major surgery therefore results in a distinct pattern of immune defects with a predominant defect in the T-cell response to T-cell receptor- and CD28 coreceptor-mediated signals rather than an impaired monocyte antigen-presenting capacity. Suppression of T-cell effector functions during the early phase of the postoperative course may define a state of impaired defense against pathogens and increased susceptibility to infection and septic complications.

Aged↗

PubMed1997

Dose-response relationship of complementary radiotherapy following four cycles of combination chemotherapy in intermediate-stage Hodgkin's disease.

PURPOSE: To determine the appropriate irradiation dose after four cycles of modern combination chemotherapy in nonbulky involved field (IF/BF) and noninvolved extended-field (EF/IF) sites in patients with intermediate-stage Hodgkin's disease (HD). MATERIALS AND METHODS: HD patients in stage I to IIIA with a large mediastinal mass, E stage, or massive spleen involvement were treated with two double cycles of alternating cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by EF irradiation in two successive trials (HD1 and HD5). In the HD1 trial (1983 to 1988), 146 patients who responded to chemotherapy were randomized to receive 20 Gy (70 patients) or 40 Gy (76 patients) of EF irradiation in all fields outside bulky disease sites. A cohort of 111 patients who fulfilled the same inclusion criteria in the subsequent trial HD5 (1988 to 1993) were treated with 30 Gy. Bulky disease always received 40 Gy. RESULTS: Freedom-from-treatment-failure (FFTF) and survival (SV) curves showed no differences between the 20-, 30-, and 40-Gy groups. However, acute toxicities were more frequent in the 40-Gy arm. Analysis of relapse patterns showed that 18 of 26 relapsing patients either failed to respond in initial bulky sites (n = 5) or had an extranodal relapse (n = 9) or both (n = 4). After 5 years, the cumulative risk for relapse in bulky sites is 10%, despite 40 Gy of radiation. CONCLUSION: Our results strongly suggest that there is no relevant radiotherapy dose effect in the range between 20 Gy and 40 Gy in IF/BF and EF/IF after 4 months of modern polychemotherapy in patients with intermediate-stage HD. Relapse patterns indicate that patients destined to relapse need more systemic, rather than local, treatment. Based on our data, we conclude that 20 Gy is sufficient in EF/IF of intermediate-stage HD following four cycles of modern polychemotherapy.

Adolescent↗

PubMed1997

[Acute renal failure].

Acute renal failure is defined as a multifactorial syndrome that occurs--depending of definition and selection of patients--in 2%-25% of all ICU patients. Most frequent in surgery (approximately 70%), ARF is caused by septic complications. Renal replacement therapy is managed today by dialysis, hemofiltration or the combination of both. Lethality of ARF ranges from 50% to 80%. High lethality rates are not related to ARF itself, but to uncontrolled septic MOF. The consequences for surgical ICU patients are: First of all, protective measures are mandatory. If ARF occurs, septic complications have to be considered. Renal replacement therapy has to be integrated into the management of septic MOF.

Acute Kidney Injury↗

PubMed1997

[Interventional therapy of intra-abdominal abscess: outcome and limits].

The postoperative course following digestive surgical procedures was prospectively analysed in 2985 patients between 6/92 and 12/96. A CT-guided percutaneous drainage of intraabdominal abscesses was performed in 144 patients (4.8%). In 123 patients (85.4%) percutaneous abscess drainage (PAD) was successful, additional surgery was not required. Twenty-one patients (14.6%) underwent additional surgery. Reasons for drainage failure were abscesses caused by internal fistulas (8 patients), pancreas involvement of the abscesses (5 patients), infected clots impossible to drain (3 patients), multiple abscesses (3 patients) and persistent abscess formation despite drainage (2 patients). Puncture-related complications were seen in 8 patients (5.5%). Puncture-related mortality was 0.7%.

Abdominal Abscess↗

PubMed1996

Determination of rifabutin by high-performance liquid chromatography using on-line concentration and column switching.

A simple HPLC method has been developed that allows the sensitive determination of rifabutin (RBT) in human serum using on-line concentration and column switching. After pretreatment of the serum with acetonitrile and centrifugation, the samples were applied to a concentration column (CC) (Zorbax CN). Washing with phosphate buffer-methanol removed most of the contaminating substances. Via a six-port valve the CC was switched to the analytical mode. RBT was separated on a Chromspher RP 8 column (acetonitrile-phosphate buffer pH 7.4/sodium chloride) and determined photometrically at 278 nm. The lower limit of quantification for 200 microliters serum precipitated with 200 microliters acetonitrile and after injection of 2 x 150 microliters was 33 micrograms/l and linearity was observed up to 27 mg/l. Different modes of sample application (single, repeated, and different injection volume portions), as well as washing time, cycle time and different CC materials were investigated.

Antitubercular Agents↗