Avascular osteonecrosis after hyperthermia in children and adolescents with pelvic malignancies: a retrospective analysis of potential risk factors.

PURPOSE: In children with locally advanced or recurrent malignant tumours, prognosis can be improved by regional deep hyperthermia (RHT) in combination with platin-based chemotherapy. However, because of the increasing number of patients that achieve long-time remission with this therapy, it is necessary to evaluate long-term sequelae of thermochemotherapy. During the years 1993-2004 one has observed avascular osteonecrosis (AON) of the femoral head after RHT in seven children with pelvic germ cell tumours or rhabdomyosarcomas. METHODS: Although AON may develop in patients with malignancies treated with chemo- or radiotherapy alone, RHT might nevertheless contribute to the occurrence of AON. In order to determine potential risk factors for AON after RHT, this study analysed the relationship of AON to the patient's age, medical history and treatment parameters such as thermal dose equivalent and power output. RESULTS AND CONCLUSIONS: In the present study AON was associated with young age as well as intensity of hyperthermia indicated by high power levels that exceed 20 W per kg body weight and/or application of eight or more heat sessions as well as additional radiotherapy. Based on this observation, it was assumed that an optimized three dimensional thermal field modelling may be helpful to avoid hazardous temperatures in the femoral heads during RHT treatment and to reduce AON of the femoral heads.     

Hypoxic ventilatory response in successful extreme altitude climbers.

A very high ventilatory response to hypoxia is believed necessary to reach extreme altitude without oxygen. Alternatively, the excessive ventilation could be counterproductive by exhausting the ventilatory reserve early on. To test these alternatives, 11 elite climbers (2004 Everest-K2 Italian Expedition) were evaluated as follows: 1) at sea level, and 2) at 5,200 m, after 15 days of acclimatisation at altitude. Resting oxygen saturation, minute ventilation, breathing rate, hypoxic ventilatory response, maximal voluntary ventilation, ventilatory reserve (at oxygen saturation = 70%) and two indices of ventilatory efficiency were measured. Everest and K2 summits were reached 29 and 61 days, respectively, after the last measurement. Five climbers summited without oxygen, the other six did not, or succeeded with oxygen (two climbers). At sea level, all data were similar. At 5,200 m, the five summiters without oxygen showed lower resting minute ventilation, breathing rate and ventilatory response to hypoxia, and higher ventilatory reserve and ventilatory efficiency, compared to the other climbers. Thus, the more successful climbers had smaller responses to hypoxia during acclimatisation to 5,200 m, but, as a result, had greater available reserve for the summit. A less sensitive hypoxic response and a greater ventilatory efficiency might increase ventilatory reserve and allow sustainable ventilation in the extreme hypoxia at the summit.     

The European Menopause Survey 2005: women's perceptions on the menopause and postmenopausal hormone therapy.

OBJECTIVES: To identify and describe current women's thoughts about the menopause, hormone treatment (HT) and perceptions about breast cancer. METHODS: Between December 2004 and January 2005, 4201 postmenopausal women in seven European countries were interviewed via a standardized computer-aided telephone interview protocol. RESULTS: Almost all women reported to have experienced climacteric symptoms, and 63% of the women rated them as being severe. Only 52% of women were aware of the benefits of HT for relief of climacteric symptoms. Although 84% felt that severe symptoms should be treated, only 40% had used HT at some point in time. Thirty-four percent of the women preferring treatment with natural products did so because of the risk of breast cancer associated with HT. HT was recognized by 59% of the women as one of the most important contributors to an increased breast cancer risk. Most women received their information about HT and breast cancer risk from the media. CONCLUSIONS: This European survey reveals that the majority of women experience climacteric symptoms but that their decision whether or not to use HT is highly dependent on their concern about breast cancer risk. An increase in knowledge of the benefits and risks of HT is required for women to make appropriate decisions about hormone use.     

Quantitative immunocytology as a marker for indications and follow-up of recurrence prevention of superficial urinary bladder cancers

In 1985, we initiated a prospective clinical trial to evaluate the risk of recurrence for superficial bladder cancer. Up to now, 41 patients subjected to TUR have subsequently been monitored by immunocytology with a monoclonal antibody (mab 486 p) recently developed in our laboratory. Of these patients, 15 (36.6%) remained marker-negative and received no prophylactic therapy. There was only one recurrence (6.7%) in this subset of patients, whereas 10 out of 26 (38.5%) marker-positive patients have so far developed recurrent malignancies. In all cases, the conversion of immunocytological characteristics preceded visible recurrence by 2-5 months. These preliminary results indicate that immunocytology might make it possible to identify patients at low risk of recurrence more accurately than has so far been feasible with standard cytology or flow-cytometry.     

Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome

Table 1     

Alternaria alternata NADP-dependent mannitol dehydrogenase is an important fungal allergen.

BACKGROUND: Alternaria alternata is one of the most important allergenic fungi worldwide. Mannitol dehydrogenase (MtDH) has previously been shown to be a major allergen of Cladosporium herbarum and cross-reactivity has been demonstrated for several fungal allergens. OBJECTIVE: The present study's objective was to clone the MtDH from an A. alternata cDNA library, express and purify the recombinant non-fusion protein and test its IgE-binding properties. Methods A cDNA library prepared from A. alternata hyphae and spores was screened for mannitol dehydrogenase by DNA hybridization with the radioactively labelled C. herbarum homologue as a probe. The resulting clone was sequenced and heterologously expressed in Escherichia coli as a recombinant non-fusion protein, which was purified to homogeneity and analysed for its IgE-binding capacity. RESULTS: The coding sequence of the full-length cDNA clone comprises 798 bp encoding a protein with a molecular mass of 28.6 kDa and a predicted pI of 5.88. Protein sequence analysis revealed an identity of 75% and a homology of 86% between the MtDHs of A. alternata and C. herbarum. The functional mannitol dehydrogenase was expressed in the E. coli strain BL21(DE3) transformed with the vector pMW172 and purified to homogeneity. The enzyme catalyses the NADPH-dependent conversion of d-fructose to d-mannitol. In IgE-ELISA and immunoblots, MtDH is recognized by 41% of A. alternata-allergic patients. In vivo immunoreactivity of the recombinant MtDH was verified by skin prick testing. Finally, inhibition-ELISA experiments confirmed cross-reactivity between the MtDHs of A. alternata and C. herbarum. CONCLUSION: Mannitol dehydrogenase (Alt a 8) represents an important new allergen of the ascomycete A. alternata that might be suitable for improving diagnostic and therapeutic procedures.     

Receptor-mediated lipoprotein transport in laying hens

In laying hens, VLDL and vitellogenin (VTG) are secreted by the liver and eventually taken up by the growing oocyte via receptor-mediated endocytosis. Both macromolecules bind to the same receptor, termed the VLDL/VTG receptor, localized on the oocyte plasma membrane. Once taken up by the growing zygote, apolipoprotein B, the major protein constituent of VLDL, is proteolytically cleaved by a chicken-specific cathepsin-D. Systemic cholesterol homeostasis in the chicken is maintained by expressing a different apoprotein B-specific receptor in somatic cells, which in terms of its function is very similar to the mammalian LDL receptor. The phenotype of the Restricted Ovulator hen, characterized by hereditary hyperlipidemia and the absence of egg laying, was identified as a lack of expression of functional VLDL/VTG receptors in the oocytes without affecting somatic apoprotein B receptors.     

The spring-back phenomenon: does the final position of the nipple areola complex correspond to the pre-operative markings in reduction mammoplasty?

This study investigates whether tissue recoil or patient intrinsic factors influence the final position of the nipple areola complex (NAC) after reduction mammoplasty. The age, pre-operative ptosis, BMI and weight of the tissue resected were recorded as patient intrinsic factors in 37 patients undergoing reduction mammoplasty. The “spring-back” value was defined as the distance from the sternal notch to a nipple landmark on the breast meridian with the patient sitting up, minus the same measurement repeated with the patient recumbent to eliminate the pull of gravity on the breast. Spring back was measured pre-operatively for the nipple and nipple mark then post-operative for the nipple. The difference in centimeters between the final post-operative distance from the sternal notch to the nipple and the level intended by the pre-operative nipple mark was termed the “judgment error.” The final position of the post-operative nipple and the judgment error was compared to the spring-back values and patient intrinsic factors. Pre-operative ptosis was statistically related to increasing patient BMI and mass of tissue resected per breast. Pre-operative spring-back values for the nipple increased with increasing ptosis, BMI and decreasing age. Spring-back values were greater in the lower pole of the breast than in the upper pole. The final position of the nipple was higher than the pre-operative mark in 65% of cases, lower in 8% and as marked in 27% of cases. The post-operative NAC was, on average, 0.6 cm higher than planned pre-operatively. The post-operative distance from the sternal notch to the nipple increased with increasing pre-operative ptosis, mass of breast tissue resected per breast and all three spring-back values. The difference between the level of the pre-operative mark and the final nipple position showed a weak correlation with post-operative spring-back values. The parameters of ptosis, BMI, weight of tissue resected per breast and pre-operative nipple spring back reflect body habitus and breast size. Spring-back values vary between the upper and lower pole of the breast. The final NAC position was higher than that intended at pre-operative marking in the majority of cases. The surgeon instinctively marks the nipple lower in patients with greater pre-operative ptosis and in whom a larger resection is anticipated. Judgment error did not relate to intrinsic factors nor to pre-operative spring-back values; hence, these parameters cannot be applied as predictive tools for more accurate pre-operative marking of the nipple position. This study suggests that the pre-operative nipple mark should be placed, with the patient sitting up, at least 23 cm from the sternal notch and 0.6 cm lower than the final position estimated using the inframammary crease as a landmark. An invited commentary on this paper is available at .