Role of radiotherapy in the treatment of multiple myeloma]

BACKGROUND: Chemotherapy is the treatment of choice in multiple myeloma; but there are no curative options. Therefore, the treatment rationale is characterized by reduction of symptoms and inhibition of complications. Regarding reduction of pain, treatment of (impending) fractures, and spinal cord compression radiation is an important part of palliative treatment. In our retrospective study we report the effect of radiotherapy on reduction of pain, recalcification and the reduction of neurological symptoms and evaluate factors which have an impact on therapeutic outcome. PATIENTS AND METHODS: From 1, Jan 1988 to 31, Dec 1998, 42 patients (19 women, 23 men; range of ages 46 to 85 years, median age 64.9 years) with 71 target volumes were irradiated (median dose 36 Gy, 2 to 3 Gy 5 times/week) because of symptomatic disease (67/71: osseous pain, 45/71: fractures/impending fractures, 13/71: spinal cord compression) (Tables 1 and 2). The median time from diagnosis to the first course of radiotherapy was 11.9 months (0.3 to 90 months). At the time of first irradiation, 5 and 37 patients were in tumor Stage II and III (Salmon/Durie), respectively. The median value of the Karnofsky performance was 70% (40 to 90%). RESULTS: During follow-up (at least 6 months) in 85% of target volumes complete and partial pain relief (measured by patients' perception and the use of analgetic medication) was achieved; recurrences were seen in 8.8%. In 26/56 (46.4%) lesions evaluable a recalcification was seen whereas 17.9% showed progressive disease (comparison of radiographs before and after radiation). In 22.3% of all lesions initially with impending fracture (4/18) radiotherapy failed because of fracture after treatment (Tables 3 and 4). Simultaneous chemotherapy and a Karnofsky performance > or = 70 had a significant impact on a positive response to treatment, respectively. Spinal cord compression symptoms were reduced in 7/13 (53.8%) of patients (scaled due to the classification by Findlay 1987). The median survival from diagnosis for the entire group was 34.9 months (7.5 to 119.3 months), after irradiation 13.1 months (0.2 to 105.3 months) (Figure 1). CONCLUSION: When adequately indicated radiotherapy has shown to be an effective palliative treatment. Taking under consideration that the results are retrospective we suppose that in multiple myeloma the local response to radiation is supported by a favorable performance status and simultaneous chemotherapy. Irradiation treatment does not change prognosis regarding overall survival.     

Transplacental transfer of monomethyl phthalate and mono(2-ethylhexyl) phthalate in a human placenta perfusion system

The transplacental passage of monomethylphtalate (mMP) and mono (2-ethylhexyl) phthalate (mEHP) was studied using an ex vivo placental perfusion model with simultaneous perfusion of fetal and maternal circulation in a single cotyledon. Umbilical cord blood and placental tissue collected both before and after perfusion were also analyzed. Placentas were obtained immediately after elective cesarean section and dually perfused in a recirculation system. mMP or mEHP was added to maternal perfusion medium to obtain concentrations at 10 and 25 microg/L, respectively. The placental transfer was followed analyzing samples from fetal and maternal perfusion media by liquid chromatography-mass spectrometry-mass spectrometry (LC-MS-MS). Four perfusions with mMP indicated a slow transplacental transfer, with a feto-maternal ratio (FM ratio) of 0.30 +/- 0.03 after 150 min of perfusion. Four perfusions with mEHP indicated a very slow or nonexisting placental transfer. mEHP was only detected in fetal perfusion media from two perfusions, giving rise to FM ratios of 0.088 and 0.20 after 150 min of perfusion. Detectable levels of mMP, mEHP, monoethylphthalate (mEP), and monobutylphthalate were found in tissue. Higher tissue levels of mMP after perfusions with mMP compared to perfusions with mEHP suggest an accumulation of mMP during perfusion. No tendency for accumulation of mEHP was observed during perfusions with mEHP compared to perfusions with mMP. Detectable levels of mEHP and mEP were found in umbilical cord plasma samples. mMP and possibly other short-chained phthalate monoesters in maternal blood can cross the placenta by slow transfer, whereas the results indicate no placental transfer of mEHP. Further studies are recommended.     

Psychometric Evaluation of the Adherence in Diabetes Questionnaire

OBJECTIVE

To assess the psychometric properties of a short, new, self-administered questionnaire (17–19 items) for evaluating the adherence behavior of children and adolescents with type 1 diabetes and their caregivers. This instrument has separate versions depending on the means of insulin administration, i.e., continuous subcutaneous insulin infusion (Adherence in Diabetes Questionnaire [ADQ]-I), or conventional insulin injection (ADQ-C).

RESEARCH DESIGN AND METHODS

A total of 1,028 caregivers and 766 children and adolescents 2–17 years of age were recruited through the Danish Registry of Childhood Diabetes and completed the national web survey, including the ADQ and psychosocial measures of self-efficacy, parental support, family conflict, and aspects of diabetes-related quality of life. Blood samples were obtained for central HbA_1c analysis. The psychometric properties of the ADQ were evaluated, and the association with glycemic control was assessed.

RESULTS

There was good internal consistency for both the youth and caregiver reports and strong agreement between the caregiver and youth reports. Higher ADQ scores, indicating better adherence, were associated with better self-efficacy, more parental support, less diabetes-related conflict, and less experience with treatment barriers. Factor analysis supported maintaining the one-factor structure of the ADQ. Higher ADQ scores were associated with lower HbA_1c levels.

CONCLUSIONS

The ADQ showed good psychometric properties. Although the test-retest reliability and sensitivity to change of the instrument still need to be established, the ADQ appears to be a valuable tool for assessing adherence in families with children and adolescents with type 1 diabetes in both clinical and research settings.It has long been acknowledged that adherence plays an important role in the glycemic control of young patients with type 1 diabetes mellitus (1). Ongoing efforts are needed to ensure that the measures used to assess adherence behavior in patients reflect the ever-evolving diabetes treatment and thus the current guidelines to which patients are expected to adhere. Even so, the increasing complexity of modern diabetes treatment poses a challenge for many of the existing measures used for evaluating adherence (2). For example, only a few self-reported instruments, such as the Self-Management of Type 1 Diabetes in Adolescents (SMOD-A) (3) and the Diabetes Behavior Rating Scale (DBRS) (4), have been able to fully adapt to the widespread use of continuous subcutaneous insulin injection (CSII). On the other hand, these measures are quite extensive, making them less suitable for studies assessing multiple components related to diabetes care.Shorter adherence measures have been used in some studies (5–7), but none adequately encompass all necessary elements of adherence in relation to diabetes care, including questions about CSII, while maintaining strong internal consistency and relevance to glycemic control.The Diabetes Self-Management Profile (DSMP) is a widely used semistructured interview for the assessment of diabetes regimen adherence (4,8) that is both relatively short and sensitive to the use of insulin pumps. However, this instrument requires the use of trained personnel to administer and to score the measure, which makes it less appropriate for larger surveys.In order to conduct a national diabetes web survey in Danish children and adolescents with type 1 diabetes, we needed a short, self-reported adherence measure that was sensitive to different treatment regimens and applicable across a relatively wide pediatric age range. Accordingly, the Adherence in Diabetes Questionnaire (ADQ) was developed to assess components of adherence behavior in this population.This report describes the development, evaluation, and validation of the self-administered ADQ and provides results about how this new instrument correlates with psychosocial variables and glycemic control.     

The RON-receptor regulates pancreatic cancer cell migration through phosphorylation-dependent breakdown of the hemidesmosome

The recepteur d'origine nantais (RON) receptor tyrosine kinase is overexpressed and stimulates invasive growth in pancreatic cancer cells, yet the mechanisms that underlie RON-mediated phenotypes remain poorly characterized. To better understand RON function in pancreatic cancer cells, we sought to identify novel RON interactants using multidimensional protein identification analysis. These studies revealed plectin, a large protein of the spectrin superfamily, to be a novel RON interactant. Plectin is a multifunctional protein that complexes with integrin-β4 (ITGB4) to form hemidesmosomes, serves as a scaffolding platform crucial to the function of numerous protein signaling pathways and was recently described as an overexpressed protein in pancreatic cancer (Bausch D et al., Clin Cancer Res 2010; Kelly et al., PLoS Med 2008;5:e85). In this study, we demonstrate that on exposure to its ligand, macrophage-stimulating protein, RON binds to plectin and ITGB4, which results in disruption of the plectin-ITGB4 interaction and enhanced cell migration, a phenotype that can be recapitulated by small hairpin ribosomal nucleic acid (shRNA)-mediated suppression of plectin expression. We demonstrate that disruption of plectin-ITGB4 is dependent on RON and phosphoinositide-3 (PI3) kinase, but not mitogen-activated protein kinase (MEK), activity. Thus, in pancreatic cancer cells, plectin and ITGB4 form hemidesmosomes which serve to anchor cells to the extracellular matrix (ECM) and restrain migration. The current study defines a novel interaction between RON and plectin, provides new insight into RON-mediated migration and further supports efforts to target RON kinase activity in pancreatic cancer.     

Dynamics of Streptococcus agalactiae colonization in women during and after pregnancy and in their infants

The population dynamics of Streptococcus agalactiae (group B streptococci [GBS]) colonization of the vagina and anorectal area was investigated in a cohort of 77 Danish women during and after their pregnancy by a new sensitive method. The mean carriage rate among individual observations was 36%, and the cumulative carriage rate over the entire observation period was 54%. Examination of more than 1500 GBS isolates by pulsed-field gel electrophoresis demonstrated that the GBS population was remarkably homogeneous and stable in each carrier. Virtually all carriers were colonized by a single GBS clone on all occasions spanning up to 2 years. Repeated detection of the same clone even in women who were recorded as intermittent carriers suggests that the actual carrier rate exceeds 50% but that fluctuations in the GBS proportions of the flora occasionally preclude their detection. Newborns and young infants usually carried the same GBS clone as their mothers. However, only twice were identical clones of GBS detected in different women in contrast to the observed clonal relationships of clinical isolates. These observations strongly suggest differences in the properties and epidemiology of virulent GBS clones compared to clones commonly carried by healthy individuals.     

A double-blind, crossover study of a sustained-release tablet of ketoprofen and normal ketoprofen capsules in the treatment of patients with osteoarthritis

A double-blind, crossover study was carried out to assess the efficacy and tolerance of a sustained-release tablet formulation of ketoprofen given as a single daily 200 mg dose compared with 2 X 50 mg normal formulation capsules of ketoprofen twice daily. Eighty-four patients with osteoarthritis of the hip and/or knee were admitted and received treatment for periods of 3 weeks, preceded by a 1-week placebo wash-out period, with each of the two formulations, in random order. Patients were seen after each study period and clinical objective and subjective assessments made of signs and symptoms of the disease, consumption of rescue analgesic and unwanted effects. Forty-eight of the patients continued, mainly on the sustained-release formulation, in an open long-term tolerance study lasting 3 months. The results were analyzed for 68 patients who completed the double-blind phase and for 33 who completed the open phase of the study. The patients who were withdrawn did so mainly for non-drug related reasons; 19 patients did so because of gastric disorders during the first phase. The incidence of side-effects was low and similar in frequency and nature with both formulations; those that were reported were mild and principally gastro-intestinal. Both active treatment periods afforded similar symptomatic relief and were preferred to placebo by all but 2 patients. No significant differences were found between active treatments, although there was a trend in favour of the sustained-release formulation for most of the parameters studied as there was in patient preference.