Changes in interface pressure and stump shape over time: preliminary results from a trans-tibial amputee subject

Interface stresses and stump shape were measured during sessions over a two-month interval on a trans-tibial amputee subject. Results from thirteen transducer sites monitored during four sessions showed greater interface pressure changes over time at anterior sites than at lateral or posterior locations. There was a trend of decreased pressure with stump swelling and increased pressure for stump atrophy. During one session in which stump shape was monitored over a 23.1 min interval after ambulation, stump swelling was localised. Swelling tended to increase in the regions of initial enlargement, as opposed to redistributing through different areas over time. Regions of swelling were anterior lateral and posterior proximal, areas of thick underlying soft tissue. Identification of localised areas of swelling and atrophy and understanding of their effects on interface pressures could be used to improve individual socket design.     

Imiquimod treatment induces expression of opioid growth factor receptor: a novel tumor antigen induced by interferon-alpha?

PURPOSE: Imiquimod represents a synthetic local immune response modifier that has demonstrated efficacy in clearing basal cell carcinoma. Via interaction with Toll-like receptor 7 on immune cells, imiquimod induces local production of cytokines, such as interferon (IFN)-alpha. EXPERIMENTAL DESIGN: To more closely define and elucidate mechanisms leading to basal cell carcinoma clearance in vivo, we examined gene expression profiles of skin basal cell carcinoma before and after treatment with 5% imiquimod cream (Aldara) by using high-density oligonucleotide arrays. RESULTS: We show that imiquimod predominantly induces genes involved in different aspects of immune response. In addition to effects on immunity, imiquimod treatment modulates the expression of genes involved in the control of apoptosis and oncogenesis. Array data indicated that imiquimod treatment induces expression of opioid growth factor receptor, a molecule recently reported to be a target for antitumor antibody responses. Immunohistochemistry revealed in vivo up-regulation of opioid growth factor receptor protein on tumor and on infiltrating cells after treatment. By using basal cell carcinoma cell lines treated with IFN-alpha or imiquimod, we show that opioid growth factor receptor up-regulation is IFN-alpha-mediated, rather then directly imiquimod-mediated. By using tissue microarray containing 52 basal cell carcinomas, we demonstrate opioid growth factor receptor expression in almost half of the cases. Expression of opioid growth factor receptor correlated with a longer recurrence-free period in basal cell carcinoma that recurred after radiotherapy (Kaplan-Meier analysis, P = 0.041). CONCLUSIONS: In addition to its immunomodulatory and antiproliferative activity, opioid growth factor receptor seems to have a prognostic significance in basal cell carcinoma patients. Our data add to the growing list of basal cell carcinoma-associated tumor antigens.     

Involvement of deprivation and environmental lead in neural tube defects: a matched case-control study

OBJECTIVE: To analyse the prevalence of neural tube defects in small geographical areas and seek to explain any spatial variations with reference to environmental lead and deprivation. SETTING: The Fylde of Lancashire in the north west of England. DESIGN: Cases were ascertained as part of a prospective survey of major congenital malformations in babies born in the Fylde to residents there between 1957 and 1981. A matched case-control analysis used infants with cardiovascular system, alimentary tract, and urinary system malformations as controls. Conditional logistic regression was used to assess the effects of more than 10 micrograms/l lead in drinking water and the Townsend deprivation score. RESULTS: The prevalence of neural tube defects in 1957-73 was higher in Blackpool, Fleetwood, and North Fylde, whereas the three control groups showed no significant spatial variation. In 1957-81 mothers living in electoral wards with either a higher proportion of houses with more than 10 micrograms/l lead in the water or a higher deprivation score had a greater risk of having a baby with a neural tube defect. For spina bifida and cranium bifidum alone, this was also true. For anencephaly, deprivation was less important although the effect of lead was still seen. In some neural tube defects, lead may act independently of other possible factors associated with deprivation. It seemed unlikely that lead levels changed significantly during the survey. The percentage of houses with 10 micrograms/l or more of lead in the water in 1984-5 was similar to that found in Great Britain 10 years previously. CONCLUSION: There is evidence to suggest that lead is one cause of neural tube defects, especially anencephaly. This could link the known preventive actions of hard water and folic acid. Calcium is a toxicological antagonist of lead. One cause of a deficiency of folic acid is impaired absorption secondary to zinc deficiency, which may be produced or exacerbated by lead.     

New non-cocaine-containing topical anesthetics compared with tetracaine-adrenaline-cocaine during repair of lacerations

OBJECTIVE: To compare the effectiveness of three new topical anesthetics that do not contain cocaine (prilocaine-phenylephrine, tetracaine-phenylephrine [tetraphen], and tetracaine-lidocaine-phenylephrine) to that of tetracaine-adrenaline-cocaine (TAC) during laceration repair in children. DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: The emergency department of an urban children's hospital. PARTICIPANTS: Children 1 year of age or older with a laceration /= 5 years of age using a visual analogue scale (VAS). Suture technicians, research assistants, and parents also scored pain using a seven-point Likert scale. In addition, suture technicians completed an anesthetic effectiveness scale. RESULTS: There was consistently no difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. A statistically significant difference was seen among anesthetics when comparing VAS and Likert scale scores of suture technicians and Likert scale scores of research assistants. Based on post hoc analyses, these statistically significant differences were between TAC and prilocaine-phenylephrine (suture technician VAS and Likert scale) and between TAC and tetracaine-lidocaine-phenyl-ephrine (suture technician Likert scale), but not between TAC and tetraphen. When power analyses were performed using alpha = 0.05 and beta = 0.20, it was possible to detect a difference of 1.2 VAS units for each of the observer groups. Based on anesthetic effectiveness scale scores, the three new topical preparations collectively performed significantly better on the face and scalp than on the extremities (relative risk = 1.83; 95% confidence interval 1.20 < relative risk < 2.79). CONCLUSION: This study demonstrated the effectiveness and safety of three new non-cocaine-containing topical anesthetics. Consistently, there was no statistical difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. Tetraphen offers an effective alternative to TAC during laceration repair in children.     

Dose-escalation, phase I/II study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS

OBJECTIVE: To assess the safety, tolerance and activity of increasing doses of azithromycin in combination with pyrimethamine for the treatment of toxoplasmic encephalitis (TE) in patients with AIDS. DESIGN: A phase I/II dose-escalation study of oral azithromycin in combination with pyrimethamine. SETTING: Eight clinical sites in the United States. PATIENTS: Forty-two adult HIV-infected patients with confirmed or presumed acute TE. METHODS: Patients were enrolled into three successive cohorts receiving azithromycin 900, 1200 and 1500 mg a day with pyrimethamine as induction therapy. The induction period was 6 weeks followed by 24 weeks of maintenance therapy. MAIN OUTCOME MEASURES: Patient response was evaluated clinically and radiologically. RESULTS: Of the 30 evaluable patients, 20 (67%) responded to therapy during the induction period. Ten experienced disease progression. Of the 15 patients who received maintenance therapy, seven (47%) relapsed. Six patients discontinued treatment during the induction period as a result of reversible toxicities. Treatment-terminating adverse events occurred most frequently among the patients receiving the 1500 mg dose. CONCLUSION: The combination of azithromycin (900-1200 mg a day) and pyrimethamine may be useful as an alternative therapy for TE among patients intolerant of sulfonamides and clindamycin, but maintenance therapy with this combination was associated with a high relapse rate. The combination was safe, but low-grade adverse events were common.