Induction of Apoptosis Reduces Immunogenicity of Human T-Cell Lines in Mice

Apoptotic cells, e.g. postinflammatory neutrophils, were reported to be engulfed by phagocytes without induction of an inflammatory response. We investigated the humoral immune response of BALB/c mice after repeated injection of viable or apoptotic human T cells. Following interleukin-2 (IL-2) deprivation, phytohaemagglutinin (PHA)/IL-2 expanded human T-cell lines were irradiated with UV-B light to induce apoptosis, confirmed by propidium iodide staining of Triton X-100-lysed cells. Indirect immunofluorescence was used to detect antilymphocyte antibodies 7 days after each injection. We found high levels of antilymphocyte antibodies in all animals immunized with viable T cells, whereas animals injected with apoptotic cells showed a significantly reduced humoral immune response. We conclude that apoptotic cells induce poor xenoreactive T-cell responses when compared with viable cells.     

Prophylactic nasal continuous positive airway pressure after major vascular surgery: results of a prospective randomized trial

BACKGROUND: The efficacy of nasal continuous positive airway pressure (nCPAP) as a prophylactic method for preventing cardiopulmonary complications after major vascular surgery has not been investigated. PATIENTS/METHODS: In a prospective randomized trial, 204 patients undergoing elective midline laparotomy for vascular surgery were randomized to receive standard therapy ( n=105) or additional prophylactic nCPAP ( n=99) for the first postoperative night. Postoperative oxygenation, incidence of severe cardiac, and pulmonary complications, length of intensive care surveillance and length of total postoperative hospital stay (LOS) were compared. RESULTS: Prophylactic nCPAP significantly reduced the number of patients with severe oxygenation disturbances defined as paO(2) < 70 mmHg with FiO(2) > or = 0.7 (5 versus 17, P=.01). There were no differences with respect to death, cardiac and pulmonary complications, length of intensive care surveillance or LOS. CONCLUSION: Prophylactic 12 h nCPAP significantly reduces the occurrence of postoperative oxygenation disturbances but has no effect on cardiac or pulmonary complications, need for intensive care, LOS or mortality after major vascular surgery.     

Extended pericranial flap and bone graft reconstruction in anterior skull base surgery.

OBJECTIVES: The objectives of this study was to establish a rationale for repairing large anterior skull base defects with an extended pericranial flap and split calvarial bone graft; to define large anterior skull base defects as those spanning the anterior cranial measuring at least 3.0 x 4.0 cm; and to describe the surgical technique and compare it with alternative strategies.Study design Thirty-four patients underwent anterior craniofacial resection of anterior skull-based tumors of varying histology with reconstruction using an extended pericranial flap and split calvarial bone graft. RESULTS: The survival of the pericranial flap and bone graft was maintained in 33 of 34 patients. There was 1 episode of postoperative cerebrospinal fluid leak, 1 episode of osteomyelitis of the bone graft and an epidural abscess, and 1 episode of asymptomatic pneumocephalus. CONCLUSION: Split calvarial bone graft with an extended pericranial flap is an effective technique for reconstructing large anterior skull base defects.     

Transforming growth factor alpha treatment alters intracellular calcium levels in hair cells and protects them from ototoxic damage in vitro

To determine if transforming growth factor alpha (TGFα) pretreatment protects hair cells from aminoglycoside induced injury by modifying their intracellular calcium concentration, we assayed hair cell calcium levels in organ of Corti explants both before and after aminoglycoside (i.e. neomycin, 10⁻³M) exposure either with or without growth factor pretreatment. After TGFα (500ng/ml) treatment, the intracellular calcium level of hair cells showed a five-fold increase as compared to the levels observed in the hair cells of control cultures. After ototoxin exposure, calcium levels in hair cells of control explants showed an increase relative to their baseline levels, while in the presence of growth factors pretreatment, hair cells showed a relative reduction in calcium levels. Pretreatment of organ of Corti explants afforded significant protection of hair cell stereocilia bundle morphology from ototoxic damage when compared to explants exposed to ototoxin alone. This study correlates a rise in hair cell calcium levels with the otoprotection of hair cells by TGFα in organ of Corti explants.     

Interpersonal distress as a mediator between avoidance goals and goal satisfaction in psychotherapy inpatients

Interpersonal behavior is assumed to be motivated by personal goals that an individual develops ontogenetically to satisfy and protect psychological needs. Interpersonal problems are hypothesized to (1) occur as a consequence of strong avoidance goals and (2) lead to decreased satisfaction of the person's approach goals. The hypotheses are tested using the self‐report data of 284 subjects with predominantly anxiety, affective and eating disorders who applied for treatment in a clinic offering inpatient cognitive–behavioral psychotherapy. Results indicate that interpersonal problems mediate the relationship between avoidance goals and the satisfaction of approach goals. Additional analyses explore specific associations between avoidance goals and certain kinds of interpersonal problem. Avoidance goals are then located within the interpersonal circle structure. Copyright © 2006 John Wiley & Sons, Ltd.     

Renale und enterale Elimination der Koproporphyrin-Isomeren bei Rotor-Syndrom

Summary Urinary and fecal total, isomer I, and isomer III coproporphyrin excretion of a Rotor's syndrome patient and his family were determined. The proprositus showed increased urinary total coproporphyrin excretion (248 µg/24 h) and a shift of the coproporphyrin isomer I/III relation (70%/30%). The propositus's father and two siblings also had elevated renal excretion of coproporphyrin I. Total coproporphyrin excretion was enhanced only in the propositus's father and one sibling, while being normal in another sibling. All family members that could be investigated showed considerably decreased fecal porphyrin excretion. In Rotor's syndrome porphyrin excretion is mainly renal. The coproporphyrin isomer I/III relation is shifted towards isomer I. Phenotypically normal relatives with normal bilirubin plasma levels may have alterations in both their renal and enteral coproporphyrin excretion.

Herrn Professor Dr. med. N. Zöllner zum 65. Geburtstag gewidmet     

Letermovir in lung transplant recipients with cytomegalovirus infection: A retrospective observational study

Letermovir is a new antiviral drug approved for the prophylaxis of CMV infection in allogeneic stem cell transplants. The aim of the study was to assess the therapeutic efficacy of letermovir in difficult to treat CMV infections in lung transplant recipients. All lung transplant recipients between March 2018 and August 2020, who have been treated with letermovir for ganciclovir-resistant or refractory CMV infection were included in the study and analysed retrospectively. In total, 28 patients were identified. CMV disease was present in 15 patients (53.6%). In 23 patients (82.1%), rapid response was noticed, and CMV-viral load could be significantly decreased (>1 log₁₀) after a median of 17 [14–27] days and cleared subsequently in all of these patients. Five patients (17.9%) were classified as non-responder. Thereof, development of a mutation of the CMV UL56 terminase (UL-56-Gen: C325Y) conferring letermovir resistance could be observed in three patients (60%). Common side effects were mild and mostly of gastrointestinal nature. Mild adjustments of the immunosuppressive drugs were mandatory upon treatment initiation with letermovir. In addition to other interventions, letermovir was effective in difficult to treat CMV infections in lung transplant recipients. However, in patients with treatment failure mutation conferring letermovir, resistance should be taken into account.     

Detection of syphilitic hearing loss.

Syphilis can cause sensorineural hearing loss that is potentially treatable. To determine the incidence of positive serological findings in patients with sensorineural hearing loss, the rapid plasma reagin card test (RPRCT) and the FTA-ABS test were performed in a study group composed of patients with sensorineural hearing loss of obscure origin. Of the 306 patients with sensorineural hearing loss, 20 (6.5%) demonstrated a positive FTA-ABS as compared with two of 100 (2%) of the control group. Considerable variation was found in the rate of the false-negative and the biological false-positive RPRCT as performed by our hospital and state laboratories when compared with the results of the FTA-ABS test. Syphilis should be considered in any patient with sensorineural hearing loss of obscure origin, despite a negative history for syphilis. The FTA-ABS is the preferred test to exclude hearing loss of syphilitic origin.     

Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment.

PURPOSE: To evaluate the time course of therapy-induced changes in tumor glucose use during chemoradiotherapy of esophageal squamous cell carcinoma (ESCC) and to correlate the reduction of metabolic activity with histopathologic tumor response and patient survival. PATIENTS AND METHODS: Thirty-eight patients with histologically proven intrathoracic ESCC (cT3, cN0/+, cM0) scheduled to undergo a 4-week course of preoperative simultaneous chemoradiotherapy followed by esophagectomy were included. Patients underwent positron emission tomography with the glucose analog fluorodeoxyglucose (FDG-PET) before therapy (n = 38), after 2 weeks of initiation of therapy (n = 27), and preoperatively (3 to 4 weeks after chemoradiotherapy; n = 38). Tumor metabolic activity was quantitatively assessed by standardized uptake values (SUVs). Results Mean tumor FDG uptake before therapy was 9.3 +/- 2.8 SUV and decreased to 5.7 +/- 1.9 SUV 14 days after initiation of chemoradiotherapy (-38% +/- 18%; P <.0001). The preoperative scan showed an additional decrease of metabolic activity to 3.3 +/- 1.1 SUV (P <.0001). In histopathologic responders (< 10% viable cells in the resected specimen), the decrease in SUV from baseline to day 14 was 44% +/- 15%, whereas it was only 21% +/- 14% in nonresponders (P =.0055). Metabolic changes at this time point were also correlated with patient survival (P =.011). In the preoperative scan, tumor metabolic activity had decreased by 70% +/- 11% in histopathologic responders and 51% +/- 21% in histopathologic nonresponders. CONCLUSION: Changes in tumor metabolic activity after 14 days of preoperative chemoradiotherapy are significantly correlated with tumor response and patient survival. This suggests that FDG-PET might be used to identify nonresponders early during neoadjuvant chemoradiotherapy, allowing for early modifications of the treatment protocol.     

Treatment of refractory Hodgkin's lymphoma patients with an iodine-131-labeled murine anti-CD30 monoclonal antibody.

PURPOSE: Hodgkin's lymphoma (HL) has been demonstrated to be a good target for immunotherapy since lymphocyte activation markers such as CD30 are expressed in high numbers on the malignant cells. Thus, we developed a new radioimmunoconjugate consisting of the murine anti-CD30 monoclonal antibody (MAb) Ki-4 labeled with iodine-131 ((131)I). PATIENTS AND METHODS: The biodistribution of (131)I-Ki-4 was assessed via dosimetry after preinfusion of 5 mg native Ki-4 followed by 250 to 300 MBq (131)I-labeled Ki-4. Whole-body scintigraphy was performed 1 hour, 24 hours, 48 hours, 72 hours, and 6 days after the infusion. Dosimetry was calculated using the programs NucliDose ICON-IDL (version 5.0.2; Siemens, Erlanger, Germany) and MIRDOSE (version 3.1; Oak Ridge National Laboratories; Oak Ridge, TN). The therapeutic dose was given on day 8 after preinfusion of unlabeled Ki-4. RESULTS: We treated 22 patients with relapsed or refractory CD30-positive HL. Preinfusion of 5 mg native Ki-4 was sufficient to bind the soluble CD30. Imaging demonstrated localization of involved areas measuring 5 cm in diameter or more in four patients and 2.5 cm in one patient. Patients received total body doses of 0.035 Gy to 0.99 Gy. Acute toxicity was mild with grade 1 fatigue in 19 of 22 assessable patients. Seven patients experienced grade 4 degrees hematotoxicity 4 to 8 weeks after treatment. Response included one complete remission, five partial remissions, and three minor responses. CONCLUSION: Treatment with (131)I-Ki-4 is effective but can be associated with severe hematotoxicity.