Late side-effects with cosmetic relevance following soft X-ray therapy of cutaneous neoplasias

Background Cosmetic changes are to be expected after radiotherapy for skin tumours. Objectives This study aimed to answer the questions: How frequent are cosmetic changes after soft X‐ray therapy? Do treatment parameters, tumour thickness, localization and size of the irradiated field have a major influence? Were patients irritated by the visual appearance of the irradiated field? Methods In total, 2474 examinations of 1149 irradiated fields were performed. Results Hypopigmentation was found in 64.7% of examinations more than 90 days after therapy, teleangiectases in 43.1%, erythema in 24.8%, and hyperpigmentation in 16.8%. The frequency of hypopigmentation, teleangiectases and hyperpigmentation increased with time from X‐ray exposure; more than 4 years after therapy hypopigmentation was diagnosed in 91.8% and teleangiectases in 82.2% of examinations. Total dose, the time–dose–fractionation factor (TDF), field size and dose per fraction were significantly related to the frequency of cosmetic changes. Incidence rates of cosmetic changes differed by less than 15% if different treatment conditions were compared: thicker vs. thinner tumours, larger vs. smaller fields, higher vs. lower total doses, doses per fraction, and TDF. Frequencies of hypopigmentation, teleangiectases, erythema and hyperpigmentation differed by more than 15% between some localizations on the head. Women reported irritation by the visual appearance of the irradiated field in 12.6% of 1116 interviews, and men in 4.4% of 1284 interviews. Conclusions Cosmetic changes after soft X‐ray therapy are relatively frequent. Treatment parameters, tumour thickness and field size have only a minor influence. Few patients, but more women than men, were irritated by the visual appearance of the irradiated field.     

Long-Term Clinical Outcomes Following Treatment of Actinic Keratosis with Imiquimod 5% Cream

BACKGROUND: The results from four phase III, randomized, vehicle-controlled studies showed that imiquimod 5% cream (imiquimod) was safe and effective in the treatment of actinic keratosis (AK). Patients applied imiquimod or vehicle cream to AK lesions on the face or balding scalp, dosing three times per week or two times per week for 16 weeks. OBJECTIVE: To obtain long-term safety follow-up data and estimate AK recurrence in patients who completely cleared their AK lesions in the treatment area at the 8-week post-treatment visit in the phase III studies. METHODS: One hundred forty-six patients from 30 study centers in the United States were evaluated for clinical evidence of AK, and safety data were collected. RESULTS: After a median follow-up period of 16 months, 24.7% (19 of 77) of the patients administered imiquimod three times per week and 42.6% (23 of 54) of the patients administered imiquimod two times per week had a recurrence of AK (the appearance of at least one AK lesion) in the original treatment area. The median number of AK lesions present was one lesion for both patients receiving imiquimod three times and those receiving imiquimod two times per week compared with a median of six lesions at baseline in the combined three times per week and two times per week phase III studies. There were no long-term safety issues, and the skin quality seen in the imiquimod-treated patients at the end of the phase III studies was maintained. CONCLUSION: One and a half years following treatment, imiquimod continued to provide a long-term clinical benefit in a majority of patients who experienced complete clearance of their AK lesions.     

Deep dermal burn injury results in scarless wound healing in the ovine fetus

Early to mid-term fetuses heal cutaneous incisional wounds without scars; however, fetal response to burn injury has not been ascertained. We present a fetal model of thermal injury and subsequent analysis of fetal and lamb response to burn injury. A reproducible deep dermal burn injury was created in the fetus by application of water at 66 degrees C for 7 seconds, and at 82 degrees C for 10 seconds to the lamb. Macroscopically, the area of fetal scald was undetectable from day 7 post injury, while all lamb scalds were readily identified and eventually healed with scarring. Using a five-point histopathology scoring system for alteration in tissue morphology, differences were detected between control and scalded skin at all stages in lamb postburn, but no difference was detected in the fetal model after day 7. There were also large differences in content of alpha-smooth muscle actin and transforming growth factor-beta1 between control and scalded lamb and these differences were statistically significant at day 14 (P < 0.01). This novel model of fetal and lamb response to deep dermal injury indicates that the fetus heals a deep burn injury in a scarless fashion. Further elucidation of this specific fetal process of burn injury repair may lead to improved outcome for patients with burn injury.     

Can true monocular keratoconus occur?

Evidence increasingly supports keratoconus as an inherited, genetic disorder. If this is the case, it would be expected to express itself as a binocular condition even though variable expression of the gene may show differing levels in the two eyes. It is a common occurrence in specialist contact lens practices to see pseudo‐monocular keratoconus, that is, an overt clinical level of the condition in one eye and forme fruste keratoconus in the other. The advent of videokeratoscopy has shown almost every case of apparent monocular keratoconus to be different expressions of the condition in the two eyes. Nevertheless, rare cases of the condition are seen that appear to be truly monocular. Such a case is presented in which the condition has been present for more than 23 years. The age of the subject makes the future onset of keratoconus highly unlikely and videokeratoscopy does not show the presence of forme fruste in the ‘good’ eye. There is no history of monocular eye rubbing. Pachymetry shows the normal eye to be well within the range of normal corneal thickness, while the keratoconus in the other eye is sufficiently advanced to warrant corneal grafting. Thus, it is a case of true monocular keratoconus and represents an extreme example of variable gene expression.     

Enhancement of in vivo and in vitro immune functions by a conformationally biased,response-selective agonist of human C5a: Implications for a novel adjuvant in vaccine design

A conformationally biased, agonist of human C5a_65–74 (EP67) was assessed for its adjuvant activities in vitro and in vivo. EP67 induced the release of the inflammatory (Th1) type cytokines from C5a receptor (CD88)-bearing antigen presenting cells (APC). EP67 did not induce the release of these cytokines from splenic APCs obtained from C5a receptor knockouts (CD88^−/−). Serum from mice immunized with EP67–ovalbumin (OVA) contained high OVA-specific antibody (Ab) titers [IgG1, IgG2a (IGg2c), IgG2b]. Mice receiving OVA alone produced only IgG1 Abs, indicating the ability of EP67 to induce a Th1-like Ab class switch. Spleen cell cultures from wild type mice but not CD88^−/− mice showed an enhanced OVA-specific proliferative response in vitro. These results indicate the ability of EP67 to drive a Th1-mediated immune response and its potential use as a unique adjuvant.     

Pituitary volume in teenagers with first-presentation borderline personality disorder

This study used magnetic resonance imaging to examine pituitary gland volume (PGV) in teenage patients with a first presentation of borderline personality disorder (BPD). No difference in PGV was observed between healthy controls (n = 20) and the total BPD cohort (n = 20). However, within the BPD cohort, those exposed to childhood trauma (n = 9) tended to have smaller pituitaries (− 18%) than those with no history of childhood trauma (n = 10). These preliminary findings suggest that exposure to childhood trauma, rather than BPD, per se, might be associated with reduced PGV, possibly reflecting hypothalamic–pituitary–adrenal axis dysfunction.     

Hypertension, antihypertensive medication and risk of renal carcinoma in California Seventh-Day Adventists

A longitudinal study of 34 198 non-Hispanic white California Seventh-day Adventists identified incident cases of renal carcinoma over six years of follow-up. The use of antihypertensive medications and self-reported hypertension had estimated age-sex adjusted incidence rate ratios of 4.51 and 2.90 respectively. These were relatively unchanged by stratifying on additional variables that may have been confounders. Cases diagnosed later during the follow-up period had the strongest association with hypertension, making the alternative explanation that the cancer may have caused the hypertension less likely. Being married in 1976 (amongst females at least) was also associated with a marked elevation of risk. Point estimates of effect suggested that frequent (greater than or equal to 3 week) consumption of fruit (RR = 0.21) and salad vegetables (RR = 0.34) may be protective for this cancer, although the 95% confidence interval did not quite exclude the null value.     

Velocity of mammalian skeletal muscle contraction as a function of fiber type, activation, initial length and temperature.

Multiple stepwise regression analyses techniques were applied to develop modifications of the Hill force-velocity equation. Specifically, predictive models of the Hill a coefficient, the Hill b coefficient, and isometric strength P0 were developed for the following set of variables: the fraction of slow-twitch fibers (X), the recruitment magnitude (A), the initial muscle length (L), and the muscle temperature (T). Results indicate that the Hill a and Hill b coefficients and isometric strength P0 can be predicted with a high degree of accuracy. The utility of the equation is that it would allow development of a computer program to control the velocity of contraction of muscles with differing fiber compositions and lengths such as are found in the leg.