Scintigraphic molecular imaging

Modern medicine is currently focusing its basic and clinical research towards "molecular medicine". This trend, together with the decoding of the human genome and the resulting design and use of transgenic mouse models of human diseases, demands that innovative imaging approaches are developed for man and mice. Non-invasive imaging modalities capable of quantifying molecular processes in vivo (collectively defined as "molecular imaging" techniques) are extremely interesting in this respect. This review focuses on the clinical and experimental scintigraphic molecular-imaging modalities SPECT and PET, and summarizes their actual and future impact in medicine.     

Case report: successful interdisciplinary treatment of cerebrally disseminated invasive pulmonal aspergillosis in a child with acute myeloid leukemia

Invasive pulmonary aspergillosis (IPA) is a life-threatening infection in immunocompromised patients. Mortality rates of cerebrally disseminated IPA approach 100%. We report on a case of a 9-year-old girl with acute myeloid leukemia, who acquired cerebrally disseminated IPA during chemotherapy-induced leukopenia. Longtime survival was achieved by left pneumonectomy and neurosurgical resection of the intracerebral lesion combined with systemic application of itraconazole and liposomal amphotericin B. A review of literature revealed 7 other cases of cerebrally disseminated IPA with survival of more than 12 months.     

Hypocitraturia as a risk factor for nephrocalcinosis after kidney transplantation

Calcium-oxalate crystal deposition in kidney transplant biopsy specimen led us to investigate the impact of calcineurin inhibitor treatment on urinary excretion of lithogenic and stone inhibitory substances in 53 children after successful kidney transplantation (KTx) receiving cyclosporine A (CsA) or tacrolimus. We compared the values obtained with those of 12 patients with recurrent nephrotic syndrome under CsA and of 6 patients with Rasmussen encephalitis (RE) under tacrolimus therapy. Renal ultrasound examinations were repeatedly performed. Hypocitraturia was found in 69% of patients, with KTx patients having a significantly lower urinary citrate excretion than those receiving calcineurin inhibitors for other reasons. Secondly, we found hyperoxaluria in 35% of patients, again especially in those after KTx. No significant difference in urinary substances was seen comparing CsA with tacrolimus treatment. Urolithiasis was found in one and calcium-oxalate crystal deposition in biopsy specimen of three KTx patients. Calcineurin inhibitor treatment can lead to significant hypocitraturia, especially in patients after KTx receiving the highest dose of medication. Hyperoxaluria is primarily the result of a removal of significant body oxalate stores, deposited during dialysis, but may not be suspected as a specific side effect of calcineurin inhibitor therapy. Both findings can increase the risk for urolithiasis or nephrocalcinosis.     

In vitro antifungal susceptibilities of Sporothrix schenckii in two growth phases

We have determined the antifungal susceptibilities of 34 clinical isolates of the dimorphic fungus Sporothrix schenckii to 11 drugs using a microdilution method. In general, the type of growth phase (mycelial or yeast) and the temperature of incubation (30 or 35 degrees C) exerted a significant influence on the MICs.     

Successful treatment of chronic recurrent multifocal osteomyelitis with tumor necrosis factor-alpha blockage

We describe the case of an 18-year-old girl with chronic recurrent multifocal osteomyelitis (CRMO) over a period of 10 years. She had suffered predominantly from very painful recurrent swelling of her cheeks. Various therapeutic regimens including nonsteroidal antiinflammatory drugs and steroids had shown only a partial or temporary response. Because tumor necrosis factor-alpha-blocking agents have been successfully applied in Crohn's-associated CRMO and the related SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome, tumor necrosis factor-alpha-blocking therapy with infliximab was initiated. Thereafter, apart from 1 mild episode, no additional recurrences were observed during 21 months of follow-up. Infliximab was well tolerated, and steroids were tapered off. Our observation indicates that infliximab may be an effective therapeutic option in CRMO.     

Expression and regulation of ROR-1 during early avian limb development

ROR-1 is a member of the ROR family of tyrosine kinase like orphan receptors and is highly conserved among various species. We have isolated the chick ROR-1 (cROR-1) and show that cROR-1 expression is high and restricted to the proximal limb region until HH-stage 25. At later stages, expression spreads towards the distal limb region. In order to determine the signals that control cROR-1 expression, factors known to be involved in limb patterning (FGFs, BMPs, SHH, retinoic acid) were applied to the developing limb. Whereas neither FGFs, BMPs, nor SHH affected cROR-1 expression, upregulation could be achieved by ectopic application of retinoic acid to the distal limb region. As retinoic acid also upregulated retinoic acid receptor beta (Rar-), we assume that cROR-1 upregulation is mediated by Rar-. We conclude that ROR-1 signaling is an independently regulated pathway, which is involved in late rather than early limb development.