Effects of metatarsal domes on plantar pressures in older people with a history of forefoot pain

Background: Forefoot pads such as metatarsal domes are commonly used in clinical practice for the treatment of pressure-related forefoot pain, however evidence for their effects is inconsistent. This study aimed to evaluate the effects on plantar pressures of metatarsal domes in different positions relative to the metatarsal heads. Methods: Participants in this study included 36 community-dwelling adults aged 65 or older with a history of forefoot pain. Standardised footwear was used and plantar pressures were measured using the pedar®-X in-shoe plantar pressure measurement system. Peak pressure, maximum force and contact area were analysed using an anatomically-based masking protocol that included three forefoot mask sub-areas (proximal to, beneath, and distal to the metatarsal heads). Data were collected for two different types of prefabricated metatarsal domes of different densities (Emsold metatarsal dome and Langer PPT metatarsal pad) in three different positions relative to the metatarsal heads. Seven conditions were tested in this study: (i) control (no pad) condition, (ii) Emsold metatarsal dome positioned 5 mm proximal to the metatarsal heads, (iii) Emsold metatarsal dome positioned in-line with the metatarsal heads, (iv), Emsold metatarsal dome positioned 5 mm distal to the metatarsal heads, (v) Langer PPT metatarsal pad positioned 5 mm proximal to the metatarsal heads, (vi) Langer PPT metatarsal pad positioned in-line with the metatarsal heads, and (vii) Langer PPT metatarsal pad positioned 5 mm distal to the metatarsal heads. Results: When analysed with the mask that was distal to the metatarsal heads, where the plantar pressure readings were at their highest, all metatarsal dome conditions led to significant reductions in plantar pressure at the forefoot compared to the control (no pad) condition (F3.9, 135.6 = 8.125, p < 0.001). The reductions in plantar pressure were in the order of 45–60 kPa. Both the Emsold metatarsal dome and the Langer PPT metatarsal pad, when positioned proximal to the metatarsal heads, managed to achieve this without adversely increasing plantar pressure proximally where the pad was positioned, however the Emsold metatarsal dome was most effective. Conclusions: Metatarsal domes reduce plantar pressure in the forefoot in older people with a history of forefoot pain. All metatarsal dome conditions significantly reduced peak pressure in the forefoot, however metatarsal domes that were positioned 5 mm proximal to the metatarsal heads provided the best balance of reducing plantar pressure distal to the metatarsal heads, where the pressure is at its greatest, but not adversely increasing plantar pressure proximally, where the bulk of the pad is positioned. In this proximal position, the Emsold metatarsal dome was more effective than the Langer PPT metatarsal pad and we cautiously recommend this forefoot pad for alleviating forefoot pressure in older people with forefoot pain

Phase I study of docetaxel plus ifosfamide in patients with advanced cancer

The aim of this study was to determine the maximum tolerated dose of a fixed dose of docetaxel when combined with continuous infusion ifosfamide, with and without G-CSF support, in the treatment of advanced cancer, and to evaluate anti-tumour activity of this combination. Thirty-one patients with advanced malignancies were treated with docetaxel 75 mg/m2 intravenously on days 1, and ifosfamide at increasing dose levels from 1500 mg/m2/day to 2750 mg/m2/day as a continuous infusion from day 1–3, every 3 weeks. A total of 107 cycles of treatment were administered. Without G-CSF support dose-limiting toxicity of grade 4 neutropenia greater than 5 days duration occurred at dose level 1. With the addition of G-CSF the maximum tolerated dose was docetaxel 75 mg/m2 on day 1 and ifosfamide 2750 mg/m2/day on days 1–3. Dose limiting toxicity (DLT) included ifosfamide-induced encephalopathy, febrile neutropenia and grade three mucositis. Three complete responses and 3 partial responses were seen. This combination of docetaxel and infusional ifosfamide is feasible and effective. The recommended dose for future phase II studies is docetaxel 75 mg/m2 on day 1 and ifosfamide 2500 mg/m2/day continuous infusion on days 1–3

Response of human HT-29 colorectal tumor cells to extended exposure to bromodeoxyuridine

Effects of the extended exposure of a human colorectal tumor-cell line (HT-29) to bromodeoxyuridine (BrdUrd) were studied in anticipation of the clinical use of that agent to treat colorectal cancer, particularly as a regionally delivered radiosensitizer. We found that 72-h exposure to a concentration of BrdUrd that is estimated to be locally maintained in the liver (100 μ M ) was significantly cytotoxic with a 3-log reduction in survival. As measured by GC/MS-SIM method, incorporation of BrdUrd into DNA followed an unexpected time course in that continuous exposure to 10 μ M BrdUrd resulted in maximal incorporation at 3 days, after which the extent of incorporated analog fell significantly (despite daily changes of the medium). This finding was apparently due to a greater rate of loss of BrdUrd from the medium at later time points. Flow cytometric analysis using an anti-BrdUrd antibody (IU-4) revealed that antibody binding also peaked and fell off with time. However, at exposure times of >24 h, the timing and extent of this decline were significantly different than had been indicated by the GC/MS method. These results indicate that the quantitative relationship between antibody staining and BrdUrd incorporation changes as drug-exposure time increases and that quantitative studies of anti-BrdUrd antibody binding must be interpreted with caution, especially when extended drug-treatment protocols have been used.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46921/1/280_2004_Article_BF00694337.pd

Diagnosis and management of Silver–Russell syndrome: first international consensus statement

This Consensus Statement summarizes recommendations for clinical diagnosis, investigation and management of patients with Silver–Russell syndrome (SRS), an imprinting disorder that causes prenatal and postnatal growth retardation. Considerable overlap exists between the care of individuals born small for gestational age and those with SRS. However, many specific management issues exist and evidence from controlled trials remains limited. SRS is primarily a clinical diagnosis; however, molecular testing enables confirmation of the clinical diagnosis and defines the subtype. A 'normal' result from a molecular test does not exclude the diagnosis of SRS. The management of children with SRS requires an experienced, multidisciplinary approach. Specific issues include growth failure, severe feeding difficulties, gastrointestinal problems, hypoglycaemia, body asymmetry, scoliosis, motor and speech delay and psychosocial challenges. An early emphasis on adequate nutritional status is important, with awareness that rapid postnatal weight gain might lead to subsequent increased risk of metabolic disorders. The benefits of treating patients with SRS with growth hormone include improved body composition, motor development and appetite, reduced risk of hypoglycaemia and increased height. Clinicians should be aware of possible premature adrenarche, fairly early and rapid central puberty and insulin resistance. Treatment with gonadotropin-releasing hormone analogues can delay progression of central puberty and preserve adult height potential. Long-term follow up is essential to determine the natural history and optimal management in adulthood