Antihormone treatment differentially regulates PSA secretion, PSMA expression and 68Ga-PSMA uptake in LNCaP cells.

BACKGROUND: In recent years, a variety of innovative therapeutics for castration-resistant prostate cancer have been developed, including novel anti-androgenic drugs, such as abiraterone or VPC-13566. Therapeutic monitoring of these pharmaceuticals is performed either by measuring PSA levels in serum or by imaging. PET using PSMA ligands labeled with Fluor-18 or Gallium-68 is the most sensitive and specific imaging modality for detection of metastases in advanced prostate cancer. To date, it remains unclear how PSMA expression is modulated by anti-hormonal treatment and how it correlates with PSA secretion. METHODS: We analyzed modulation of PSMA-mRNA and protein expression, 68Ga-PSMA uptake and regulation of PSA secretion by abiraterone or VPC-13566 in LNCaP cells in vitro. RESULTS: We found that abiraterone and VPC-13566 upregulate PSMA protein and mRNA expression but block PSA secretion in LNCaP cells. Both anti-androgens also enhanced 68Ga-PSMA uptake normalized by the number of cells, whereas abiraterone and VPC-13566 reduced 68Ga-PSMA uptake in total LNCaP monolayers treated due to cell death. CONCLUSION: Our data indicate that PSA secretion and PSMA expression are differentially regulated upon anti-androgen treatment. This finding might be important for the interpretation of 68Ga-PSMA PET images in monitoring therapies with abiraterone and VPC-13566 in prostate cancer patients, but needs to be validated in vivo.

[THE MALADAPTIVE BELIEFS OF PATIENTS WITH LOW BACK PAIN. A NARRATIVE REVIEW]. / LES CROYANCES DÉLÉTÈRES DES PATIENTS LOMBALGIQUES. Revue narrative de la literature.

OBJECTIVE: to summarize the knowledge regarding the maladaptive beliefs of patients with non-specific low back pain. METHODS: a narrative literature review on these beliefs was conducted by an international and multidisciplinary team of experts in the field. RESULTS: these beliefs, which can result in negative consequences on functioning and on patient prognosis, have various origins: family and friends, media, previous experience and/or health care professionals' messages. The latter, who have a considerable and enduring influence, have the potential to change and correct the patients' misbeliefs; however, they can also reinforce them in case of inappropriate messages and attitudes. Informing and educating the patient (by means of reassurance, explanations of the non-systematic association pain-injury, encouragement to get and stay physically active) are the basis of treatment. Taking into account the consequences of some words which may be misinterpreted, the results of imaging should be wisely discussed with the patient. Pain neurophysiology education and cognitive behavioral therapy (i.a., in vivo graded exposure techniques) are effective additional treatments. CONCLUSIONS: Misbeliefs are frequent in patient with low back pain. They do need to be looked for and corrected.

Volition and low back pain: When patients talk.

OBJECTIVE: Our objective was to explore, describe and understand volition of chronic low back pain (LBP) patients, highlighting barriers and facilitators to practicing regular physical activity in order to develop a questionnaire assessing those volitional competencies. METHODS: A content analysis of semi-structured interviews with 30 chronic LBP patients was performed. Participants were asked about their pain, motivation, physical abilities, barriers and facilitators to regular exercises and finally strategies implemented to achieve the exercise program. RESULTS: Patients often reported that they were motivated and that exercises had no negative effects on LBP. Many patients recognized having difficulties performing all their exercises regularly. The main barriers were: lack of time, fatigue, lack of visible results, pain and other daily priorities. The main facilitators were: group exercise, help from the therapist, strategic planning, favorable environment, pleasure associated with exercises, fear of pain recurrence and pain itself. CONCLUSION: Content analysis showed that sharing stories allowed patients to express their experience of LBP in their own words. It provides a solid ground to develop a questionnaire assessing volitional competencies in chronic LBP patients in order to identify patients who will not realize their exercises and help them be (more) active and avoid chronicity.

[Modelling of length of stay and costs in 2 homogeneous groups of hematological and pneumological patients: clinical characterization of patients with long-stay and high costs]. / Modélisation de la distribution des durées de séjour et des coûts dans deux groupes homogènes de malades d'hématologie et de pneumologie: caractérisation clinique des patients de longue durée et de coût élevé.

After the implementation of the Medicare Prospective Payment System (PPS) in the USA, many European countries like France have introduced DRGs to curb hospital overspending. However, there has been some reluctance from hospital actors, especially because of the heterogeneous nature of DRG's. To analyse this situation, we propose a method based on distribution modelization of length of stays and costs within DRGs. For each DRG, the model is based on a mixture of Poisson and Weibull distributions identified as subgroups. The subgroups are characterized by their means and their proportions which are estimated by maximization of data likelihood. For a particular DRG, the proportion of long stay or high-cost patients can be explained by the introduction of clinical variables in the model. First the model was applied to the DRG "leukemia and lymphoma" (HCFA V.3), using 133 discharge abstract files from the Dijon public teaching hospital which were classified into this DRG in 1993. Among the studies parameters only acute leukemia, neutropenia < 500 PNN/mm3, high dose aplastic chemotherapy, central venous catheterization, parenteral nutrition, use of protected or laminar air flow room, septicemia, large spectrum intravenous antibiotherapy, and blood transfusion had a significant influence on the distribution of the patients in the long stay or costly subgroup. Second, for DRG "chronic bronchopneumopathies" (n = 220) the significant parameters were mechanical ventilation, antibiotherapy, post hospitalization medicalized care.

Structural and conjunctural compensation method for hospital budgetary allocation on the basis of DRGs.

We propose here a structural and conjunctural compensation method to improve budgetary allocation which could be based on Diagnosis Related Groups. This method consists in the determination of sub-group costs within DRGs. The specification of these sub-groups is possible by introducing clinical and social parameters in the statistical model. Hospitals could then compare their sub-group proportions and analyze their differences in relation to conjunctural factors (recruitment, medical practices) and structural factors (technical team, local medical structure). This method also allows an identification of specialty hospitals (outliers) and a compensation allocation for budgeting for these hospitals.

[Polyamines and cardiovascular hypertrophy in experimental hypertension]. / Polyamines et hypertrophie cardiovasculaire dans l'hypertension expérimentale.

UNLABELLED: Biochemical mechanisms which control cardiac and vascular response to hypertension are still unclear. Modifications of polyamines (putrescine, spermine, spermidine) may play a role in this phenomenon, since these molecules have been shown of importance in the control of tissue growth. Ornithine Decarboxylase (ODC) catalyses the first and probably the rate limiting step in the biosynthesis of the polyamines. We thus attempted to detect modification of ODC activity in renovascular hypertension in the rat (G1K-1C) and tried to correlate hypertrophic response and ODC activity in the aorta (Ao), the left (LV) and the right (RV) ventricles. In this experimental model, the aortic ODC activity increased at day 1 and 2, after clipping the renal artery, whereas in the LV the ODC activity increased after day 3 but stay high at least until day 7. The peak of ODC activity comes before the increase in DNA synthesis which occurs at day 4 in Ao, and the increase in protein turnover observed at day 7 in LV. No significant variation of ODC activity neither changes in DNA or protein biosynthesis rate are observed in the RV. In parallel with changes in ODC activity, an increase in spermidine and spermine content and mainly in the spermidine/spermine ratio is observed in the Ao and the LV confirming stimulation in polyamine biosynthesis in hypertensive tissues. IN CONCLUSION: increase in ODC activity is observed only in these tissues that will develop hypertrophy or hyperplasia and this modification is observed before any increase in nucleic acids or protein tissues content or turnover rate.