[Rare cause of necrotizing pneumonia : A case report]. / Seltene Ursache einer einschmelzenden Pneumonie : Ein Fallbericht.

A 29-year-old Indian patient was admitted to the authors' pulmonary clinic with cough and fever. Community-acquired pneumonia was initially suspected. Various antibiotic therapies were administered, which did not lead to any clinical improvement. Despite detailed diagnostics, no pathogen was found. Computed tomography showed rapidly progressive pneumonia in the left upper lobe. Since the infection could not be managed conservatively, upper lobe resection was performed. Histologically, an amoebic abscess was found to be the cause of the infection. Since cerebral and hepatic abscesses were also found, hematogenous dissemination may be assumed.

Type 4 hypersensitivity development in a case due to mifamurtide.

BACKGROUND: This report aims to discuss the mechanism of pleural and pericardial effusion related to mifamurtide which is an immunological agent used as adjuvant chemotherapy in osteosarcoma. CASE: Mifamurtide (2 mg/m < sup > 2 < /sup > ) and European and American Osteosarcoma Studies (EURAMOS) protocol were used together intravenously after complete surgical resection. No side effects occurred except for fever after the first dose. However, pleural, pericardial effusion, and splenic nodule formation began 11 months after discontinuation of mifamurtide treatment. Pleural biopsy revealed a type 4 hypersensitivity reaction. We treated the patient with 1,5 mg per day colchicine. Pericardial effusion attacks and nodules in the spleen disappeared. The patient had a mild pleural effusion attack which has not yet repeated. CONCLUSION: Mifamurtide, which activates macrophages, can also activate immunity with a stand by effect and cause a hypersensitivity reaction.

Skinfold thickness of preterm newborns when they become late preterm infants.

BACKGROUND: Nutrition of very low-birth-weight newborns is important for a good physical and neurologic outcome. Body composition assessment, together with anthropometric measurements, is considered necessary to monitor adequate nutrition and growth. Objectives of this study were to assess body fat changes in newborns ≤32 weeks gestation by weekly skinfold thickness (SFT) measurements and to compare them with those of late preterm infants born at 34, 35, and 36 weeks once they reached 34, 35, and 36 weeks corrected age (CA). MATERIALS AND METHODS: Preterm infants ≤32 weeks gestation had SFT measured from 4 body sites, including biceps, triceps, and subscapulary and suprailiac regions, by a Holtain caliper starting from 48 hours of age at weekly intervals until 34, 35, and 36 weeks CA. The measurements were compared with those of late preterm controls born at 34, 35, and 36 weeks gestation. RESULTS: There were 37 preterm infants in the patient group. When reaching 34, 35, and 36 weeks CA, preterm infants had higher SFT values compared with controls in all body sites. Median and range of total SFT were 14.6 mm (9.6-18.9 mm) in patients and 11 mm (7.8-16.4 mm) in controls at 34 weeks CA, 15.5 mm (10.7-21.8 mm) in patients and 12.3 mm (7-17 mm) in controls at 35 weeks CA, and 16.4 mm (11.8-23.7 mm) in patients and 12.9 mm (7-17.8 mm) in controls at 36 weeks CA (P = .001 in all). No sex difference was observed at 34 and 35 weeks. CONCLUSION: These results show that preterm infants start accumulating excess fat even from early weeks of life. Careful assessment of growth by tools other than simple anthropometric measurements is essential to avoid future complications.

Synergistic antimyeloma effects of zoledronate and simvastatin.

Despite advances in the treatment of multiple myeloma, it remains an incurable disease because of primary and secondary drug resistance. Mevalonate pathway inhibitors like bisphosphonates and statins have antimyeloma activity in vitro at very high concentrations, which may probably not be reached in vivo. NCI-H929, OPM-2, U266 and RPMI-8226 myeloma cell lines were treated in the presence or absence of bone marrow stromal cells with simvastatin or zoledronate in combination with classical antimyeloma drugs like melphalan or bortezomib. Zoledronate did not show substantial antimyeloma activity at low and intermediate concentrations, whereas simvastatin potently induced apoptosis in myeloma cells without signs of primary, cell-adhesion-mediated drug resistance. Furthermore, sequential blockage of the mevalonate pathway by zoledronate and simvastatin demonstrated synergistic induction of apoptosis and reversal of cell-adhesion-mediated drug resistance. Our data provide a rationale for combining zoledronate and simvastatin with classical antimyeloma drugs.

The HMG-CoA reductase inhibitor simvastatin overcomes cell adhesion-mediated drug resistance in multiple myeloma by geranylgeranylation of Rho protein and activation of Rho kinase.

Primary drug resistance is a major problem in multiple myeloma, an incurable disease of the bone marrow. Cell adhesion-mediated drug resistance (CAM-DR) causes strong primary resistance. By coculturing multiple myeloma cells with bone marrow stromal cells (BMSCs), we observed a CAM-DR of about 50% to melphalan, treosulfan, doxorubicin, dexamethasone, and bortezomib, which was not reversed by secreted soluble factors. Targeting the adhesion molecules lymphocyte function-associated antigen 1 (LFA-1) and very late antigen 4 (VLA-4) by monoclonal antibodies or by the LFA-1 inhibitor LFA703 reduced CAM-DR significantly. Only statins such as simvastatin and lovastatin, however, were able to completely restore chemosensitivity. All these effects were not mediated by deadhesion or reduced secretion of interleukin 6. Targeting geranylgeranyl transferase (GGTase) and Rho kinase by specific inhibitors (GGTI-298 and Y-27632), but not inhibition of farnesyl transferase (FTase) by FTI-277, showed similar reduction of CAM-DR. Addition of geranylgeranyl pyrophosphate (GG-PP), but not of farnesyl pyrophosphate (F-PP), was able to inhibit simvastatin-induced CAM-DR reversal. Our data suggest that the 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA)/GG-PP/Rho/Rho-kinase pathway mediates CAM-DR and that targeting this pathway may improve the efficacy of antimyeloma therapies by reduction of CAM-DR.