Prevention of palmoplantar erythrodysesthesia in patients treated with pegylated liposomal doxorubicin (Caelyx®).

PURPOSE: Palmoplantar erythrodysesthesia (PPE) is one of the most frequent side effects during systemic treatment with pegylated liposomal doxorubicin (PLD, Caelyx®). PPE lesions show a range of symptoms, from numbness to painful erosions, and can have a major impact on the quality of life in affected patients. Previously, a possible pathomechanism of PPE was found in doxorubicin-treated patients based on radical formation in the skin. Here, a preventive strategy using a topically applied ointment with a high radical protection factor was investigated. METHODS: In this randomized placebo-controlled double-blind study the antioxidant-containing ointment was compared with a placebo ointment regarding PPE grade III occurrence, overall PPE grade I-III occurrence and PPE severity in PLD patients. The verum or placebo cream was topically applied for a period of 16 weeks, starting 3 days prior to the first cycle of chemotherapy. Clinical evaluations were carried out by a dermatologist prior to the first cycle of chemotherapy and every 4 weeks for the duration of 16 weeks. RESULTS: Thirty-two patients were enrolled in total, of which 17 (66%) completed the study. No PPE grade III was found in the verum group, while five out of seven patients (71%) had to be unblinded in the placebo arm due to PPE grade III (p = 0.003). General PPE occurrence of all grades was 60% under verum and 86% under placebo treatment. CONCLUSIONS: The preventive application of an antioxidant-containing ointment was shown to be significantly more effective in the prevention of PPE grade III compared to placebo treatment.

[Bilateral bisphosphonate-associated osteonecrosis of the external ear canal : a rare case]. / Beidseitige bisphosphonatassoziierte Osteonekrose des Gehörgangs : Ein seltener Fall.

Osteonecrosis of the mandible is a well-known and dreaded complication after the administration of bisphosphonates. Only a few cases of bisphosphonate-associated osteonecrosis of the external ear canal have been described. Especially after long-lasting bisphosphonate therapy, for example in patients with multiple myeloma, an ulceration of the floor of the bony external auditory canal should be treated surgically and be distinguished from radioosteonecrosis, malignant external otitis, or carcinoma of the external ear.

The N-terminal part of the E.coli DNA binding protein FIS is essential for stimulating site-specific DNA inversion but is not required for specific DNA binding.

FIS protein is involved in several different cellular processes stimulating site-specific recombination in phages Mu and lambda as well as transcription of stable RNA operons in E.coli. We have performed a mutational analysis of fis and provide genetic and biochemical evidence that a truncated version of FIS lacking the N-terminal region is sufficient for specific DNA binding and for stimulating lambda excision. These mutants also retain their ability to autoregulate fis gene expression. Such mutant proteins, however, cannot stimulate the enhancer dependent DNA inversion reaction.

Site-specific recombination in bacteriophage Mu: characterization of binding sites for the DNA invertase Gin.

Site-specific DNA inversion in phage Mu is catalysed by the phage-encoded DNA invertase Gin and a host factor FIS. We demonstrate that purified Gin protein binds specifically to 34-bp sequences that flank the G segment as inverted repeats. Each inverted repeat (IR) contains two binding sites for Gin which have to be arranged in a specific configuration to constitute a recombinogenic site. While one of these sites is bound when present alone, the other site is bound only in conjunction with the first one, suggesting cooperative binding. In addition to the sites within the IR, Gin binds with lower affinity to AT-rich sequences adjacent to the IR. We demonstrate that these sites do not participate in the inversion reaction. The IR itself can be shortened to 25 bp without effect on inversion frequency. Using gel mobility shift experiments on circular permuted fragments containing the IR we show that Gin bends DNA upon binding. We discuss the possibility that DNA bending is related to the formation of a productive synaptic complex.

Purification and properties of the DNA invertase gin encoded by bacteriophage Mu.

The host range of bacteriophage Mu is regulated through an invertible segment. Inversion requires the presence of two properly oriented recombination sites and a recombinational enhancer sis. The reaction is catalyzed by the Mu-encoded DNA invertase Gin and a host factor termed factors for inversion stimulation (FISs). We present a novel purification scheme for Gin. Purified Gin alone catalyzes the inversion reaction at very low efficiency recombining less than 0.8% of substrate molecules. When supplemented with FIS substrates containing the recombinational enhancer are recombined efficiently. Stoichiometric amounts of Gin are required for recombination.

[The variation of the depth of the cervices in the ground surface of the tooth]. / Die Variation der Ritztiefe auf der Schliffoberfläche eines Zahnes

Variations in the depth of scratches in a transverse section of a premolar was studied. The scratches were produced by a Vickers diamond whose vertical deviations during scratching were measured by an inductive distance recorder and continually registered by an xy-recorder. The depth of scratches in all areas of the enamel was almost constant with only minimal variation. In the dentine, too, the variations were small, the constant being greater than in the enamel. The greatest depth was measured in interglobular dentine.