A 2-year, randomized, comparative, placebo-controlled study on the effects of raloxifene on lipoprotein(a) and homocysteine

OBJECTIVES: Lipoprotein(a) (Lp(a)) and homocysteine (Hcy) are independent cardiovascular risk factors, which have been shown to be lowered by hormone replacement therapy (HRT). In this 2-year study, the long-term effects of raloxifene (Rlx) in two doses, on Lp(a) and Hcy, were studied and compared with the effects of continuously combined hormone replacement therapy (ccHRT). METHODS: In a prospective, randomized, double-blind, placebo-controlled 2-year study, 95 healthy, non-hysterectomized, early postmenopausal women, received daily either oral Rlx 60 mg (N=24) or 150 mg (N=23), ccHRT (conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg; N=24) or placebo (N=24). Fasting serum Lp(a) and plasma Hcy concentrations were measured at baseline and at 6, 12 and 24 months. RESULTS: The mean individual changes compared to baseline after 24 months were for Lp(a): Rlx 60: - 5%, Rlx 150: -7%, ccHRT: -34%, placebo: +1% and for Hcy: Rlx 60: -3%, Rlx 150: -4%, ccHRT: -4%, placebo: +6%. ANCOVA was significant for Lp(a) under ccHRT versus placebo (P=0.001) and for Lp(a) under ccHRT versus each of the two Rlx groups (P<0.05). CONCLUSIONS: Long-term treatment with Rlx was not as effective as ccHRT in lowering Lp(a). Although not significant and without an obvious dose-related response, the Hcy values showed the same trend for each treatment arm, which is in line with data reported earlier.     

A Risk Scoring System to Determine Recurrence in Early-Stage Type 1 Endometrial Cancer: A French Multicentre Study

Background

To develop a risk scoring system (RSS) to determine recurrence in women with early-stage type 1 endometrial cancer (EC).

Methods

Data of 396 women with early-stage type 1 EC who received primary surgical treatment between January 2001 and December 2012 were abstracted from multicentre database (training set). A risk model for predicting recurrence was developed and internally validated with the bootstrap technique. The RSS was externally validated using data from an independent population.

Results

Overall, the recurrence rate was 12.1 %. The median follow-up and initial time to recurrence were 34 (range 1–152) and 26 (range 1–151) months, respectively. Recurrence was associated with five variables: age ≥60 years, histological grade III, primary tumor diameter >2 cm, depth of myometrial invasion ≥50 %, and the positive lymphovascular space involvement status. These variables were included in the RSS and assigned scores. A total score of 6.5 points corresponded to the optimal threshold of the RSS. For women with a score <6.5 or ≥6.5, the recurrence rates were 8.4 % (30/357) and 48.7 % (19/39) in the training set, respectively. At this threshold, the diagnostic accuracy of the RSS was 87 %. Areas under the curve of the receiver-operating characteristics for predicting recurrence at internal and external validation were 0.74 [95 % confidence interval (CI) 0.71–0.77] and 0.82 (95 % CI 79–85), respectively.

Conclusions

This RSS identified two subsets of women with low and high risk of recurrence among women with early-stage type 1 EC. It could be helpful to better define indications for nodal staging and adjuvant therapy.     

In situ transformation of glass-ionomer into an enamel-like material

PURPOSE: To assess the nature of clinically detectable alterations in glass-ionomer after long-term clinical service. METHODS: In addition to clinical macro pictures, SEM was carried out on replicas and on two sectioned primary molars SEM-EDAX analysis was performed to determine chemical transformation in the glass-ionomer. Also with SEM-EDAX, the composition was determined of a partially removed half-year old sealant. RESULTS: The clinically observed altered optical aspect and increased hardness could be related with surface structure changes as identified by SEM. The changed glass-ionomer showed a continuous integration with the adjacent enamel. The SEM-EDAX analysis revealed an increase of calcium and phosphorus in the surface layer, tentatively suggesting a sort of additional "mineralization" of the material. This phenomenon was only observed for restorations that had minimally 2-3 years in vivo dwell time.     

Randomized prospective study comparing high-dose-rate intraluminal brachytherapy (HDRILBT) alone with HDRILBT and external beam radiotherapy in the palliation of advanced esophageal cancer

PURPOSE: HDRILBT is one of the best methods of palliation for advanced esophageal cancer (AEC) by improving dysphagia-free survival (DFS) and overall survival (OS). This study examines if the addition of EBRT would further improve the outcome by improving DFS in AEC. METHODS AND MATERIALS: Patients with inoperable AEC were entered into a randomized prospective study. HDRILBT of 16 Gy/2 fractions/3 days was given initially to all patients. Following treatment, patients were randomized to receive no further treatment (Group A) or additional EBRT of 30 Gy/10 fractions/2 weeks (Group B) and were followed for 1 year. Statistical analysis of the data was done using the SAS statistical software package (SAS Institute, Cary, NC). Prognostic variables were analyzed using the chi(2) and log-rank tests and survival curves were drawn using the Kaplan-Meier method. Multivariate survival analysis was done using the Cox proportional hazards model. RESULTS: Sixty patients were entered into the study. Patient and tumor characteristics were comparable among the groups. Of 30 patients in Group B, 2 refused additional EBRT (no dysphagia). At 6 months, >50% had DFS in both groups and this was comparable. There was no difference statistically (p >0.05) in the DFS and OS between the two groups at the end of 12 months. Median survival for Group A was 7.23 months and 7.5 months for Group B. Additional EBRT did not improve DFS or OS. Eleven patients developed strictures related to radiotherapy and were dilated successfully (Group A, 7; Group B, 4; p >0.05). Four patients had progressive luminal disease which progressed to fistula (Group A, 3; Group B, 1; p >0.05). There was no effect of any patient or treatment parameter on DFS. Presenting weight and ECOG score had an impact on OS. CONCLUSIONS: From the preliminary analysis, additional EBRT to HDRILBT does not improve DFS or outcomes in inoperable AEC.     

Increased binding of anti-acetylcholine receptor antibodies to thymic antigen in patients with myasthenia gravis and other autoimmune diseases, as compared to those with myasthenia gravis alone

We compared the binding activity against acetylcholine receptors solubilized from human muscle (AChRM) and human thymus (AChRT), of sera from patients with myasthenia gravis (MG) alone, to those of sera from patients with myasthenia gravis and associated autoimmune diseases (MG AD). The sera of the MG AD group bound relatively better to thymic antigen (86% vs. 62%). This group was found to contain a higher proportion of women over 40 years of age (more than 50% of the group). The expression of a particular AChR antigen in normal human thymus may be one of the factors involved in the pathogenesis of MG, especially when this disease is associated with other autoimmune disorders.     

Alternative Medicine Techniques Have Non-Linear Effects on Radiation Response and Can Alter the Expression of Radiation Induced Bystander Effects

Many so-called “alternative medicine” techniques such as Reiki and acupuncture produce very good outcomes for intractable pain and other chronic illnesses but the efficacy is often dismissed as being psychosomatic. However a plausible mechanism does exist i.e. that the treatments alter the electromagnetic fields in living organisms and thereby prevent or reduce activity of neurons which lead to the pain. Low doses of ionising radiation have similar effects on electromagnetic fields and are known to induce signaling cascades in tissues due to ion gradients. To test this hypothesis cell cultures were exposed to Reiki – like and to acupuncture – like treatments, both performed by qualified practitioners. The cells were exposed either before or after the treatment to x-rays and were monitored for production of direct damage or bystander signals. The data suggest that the alternative techniques altered the response of cells to direct irradiation and altered bystander signal mechanisms. We conclude that alternative medicine techniques involving electromagnetic perturbations may modify the response of cells to ionizing radiation. In addition to the obvious implications for mechanistic studies of low dose effects, this could provide a novel target to exploit in radiation protection and in optimizing therapeutic gain during radiotherapy.     

Nocardiosis following solid organ transplantation: a single-centre experience.

Nocardiosis is a localized or disseminated bacterial infection caused by aerobic Actinomyces that commonly affects immunocompromised hosts. The aim of this study was to retrospectively review clinical course and outcome of nocardiosis in solid organ recipients at our centre. Five cases of nocardiosis were identified in a series of more than 4000 consecutive solid organ transplants performed at Innsbruck university hospital during a 25-year period. Of the five patients with nocardiosis, two had undergone multivisceral, one liver, one kidney and one lung transplantation. Three patients with Nocardia asteroides infection were treated successfully and recovered from their infectious disease, however, one lost his renal graft following withdrawal of immunosuppression. The lung recipient recovered from nocardiosis but died later on from Pseudomonas pneumonia. One multivisceral recipient died from Nocardia farcinica-disseminated infection. Nocardiosis is a rare, difficult-to-diagnose-and-treat complication following solid organ transplantation. Intestinal recipients might be at increased risk to develop this infection.