Exploratory study of metacognitive beliefs about coping processes in prolonged grief symptomatology

Despite research examining the role of metacognitive beliefs about coping processes in maintaining psychological disorders, to date, no studies have explored their role in the maintenance of prolonged grief. Twelve semistructured interviews were conducted with bereavement specialists and bereaved people with elevated grief to identify metacognitive beliefs about coping processes relevant to prolonged grief. Analysis revealed several metacognitive beliefs potentially driving maladaptive coping processes used by people with prolonged grief symptomatology. Findings may underpin the development of interventions that aim to modify unhelpful metacognitive beliefs that perpetuate maladaptive coping processes.     

Stage II adenocarcinoma of the endometrium treated by two standard regimens of combined preoperative irradiation and surgery

We retrospectively analyzed 77 patients with stage II endometrial carcinoma treated with standard regimens of preoperative radiotherapy (RT) and surgery (S). The age range was 31–74 years with a median of 56.3 years. Thirty-three patients received 40 Gy whole pelvis RT followed by either radical or modified radical hysterectomy. Forty-four patients received 50 Gy whole pelvis RT and sequential intrauterine and intravaginal cesium-137 brachytherapy followed by a simple hysterectomy. Median follow-up was 111 months. No patient was lost to follow-up. The overall 5-year actuarial survival was 78%. There was no significant difference between the two treatment groups. Several prognostic variables were analyzed. Those with histologic grade I and II had 5-year survival of 89% and 83%, respectively, compared to 62% for grade III ( P =0.045). The 5-year survival for microscopic cervical involvement was 87% compared to 59% for gross involvement ( P = 0.008). Patients with negative or microscopic residual tumor in the surgical specimen and those with negative lymph nodes had less risk of treatment failure. Local failure occurred in only 9%. Major complications (3%) were seen only in the radical surgery group. Combined preoperative RT and S provide high cure rates with minimal complications for patients with stage II endometrial carcinoma. Patients with adverse prognostic factors are candidates for trials of more aggressive local and systemic therapy.     

The novel toluidine sulphonamide EL102 shows pre-clinical in vitro and in vivo activity against prostate cancer and circumvents MDR1 resistance

Background:

Taxanes are routinely used for the treatment of prostate cancer, however the majority of patients eventually develop resistance. We investigated the potential efficacy of EL102, a novel toluidine sulphonamide, in pre-clinical models of prostate cancer.

Methods:

The effect of EL102 and/or docetaxel on PC-3, DU145, 22Rv1 and CWR22 prostate cancer cells was assessed using cell viability, cell cycle analysis and PARP cleavage assays. Tubulin polymerisation and immunofluorescence assays were used to assess tubulin dynamics. CWR22 xenograft murine model was used to assess effects on tumour proliferation. Multidrug-resistant lung cancer DLKPA was used to assess EL102 in a MDR1-mediated drug resistance background.

Results:

EL102 has in vitro activity against prostate cancer, characterised by accumulation in G2/M, induction of apoptosis, inhibition of Hif1α, and inhibition of tubulin polymerisation and decreased microtubule stability. In vivo, a combination of EL102 and docetaxel exhibits superior tumour inhibition. The DLKP cell line and multidrug-resistant DLKPA variant (which exhibits 205 to 691-fold greater resistance to docetaxel, paclitaxel, vincristine and doxorubicin) are equally sensitive to EL102.

Conclusion:

EL102 shows potential as both a single agent and within combination regimens for the treatment of prostate cancer, particularly in the chemoresistance setting.     

NITRIC OXIDE-DEPENDENT ENDOTHELIAL FUNCTION IS UNAFFECTED BY ALLOPURINOL IN HYPERCHOLESTEROLAEMIC SUBJECTS

1. Hypercholesterolaemia is associated with abnormal endothelium-related vasodilator function, possibly due to increased destruction .NO by superoxide anions (.O2-). Oxypurinol, a xanthine oxidase (XO) inhibitor with anti-oxidant properties and the active metabolite of the commonly used drug allopurinol, reduces .NO quenching in vitro and has been reported to acutely improve endothelial function in hypercholesterolaemic subjects. 2. The purpose of the present study was to determine whether oral allopurinol improves .NO dilator function in hypercholesterolaemic subjects. 3. A randomized double-blind, placebo-controlled cross-over design evaluated the effect of allopurinol (300 mg daily for 4 weeks) on forearm blood flow (FBF) responses to intrabrachial infusion of acetylcholine (ACh), sodium nitroprusside (SNP) and NG-monomethyl-L-arginine (L-NMMA) in nine hypercholesterolaemic subjects. 4. Endothelium-dependent vascular responses to ACh and L-NMMA were not significantly altered by allopurinol. The endothelium-independent vasodilator response to SNP was similarly unchanged. 5. These results indicate that allopurinol does not influence basal or stimulated activity of the .NO dilator system in hypercholesterolaemic subjects. If intracellular .O2- inactivation .NO is responsible for endothelial dysfunction in hypercholesterolaemia, the source may be other than XO dependent. However, generation of .O2- during the conversion of allopurinol to oxypurinol could offer an alternative, and probably more likely, explanation for the ineffectiveness of allopurinol in vivo.