Feasibility of an ovarian cancer quality-of-life psychoeducational intervention

Background. Diagnosis of ovarian cancer often portends a poor prognosis with significant quality-of-life (QOL) concerns. Method. We report on a pilot study that tested the feasibility of a structured, ovarian cancer psychoeducational intervention (OCPI). Patients (N=33) were randomly assigned to either the control or OCPI study arms in which those in the intervention arm received 4 sequential, structured, in-person educational sessions. Data were collected at the time of accrual and at 1 and 3 months postaccrual. Results. This study demonstrated the feasibility of a structured psychoeducational program in an outpatient clinical setting. Conclusion. Study findings underscore the importance of developing interventions that address the 4 QOL domains impacted by ovarian cancer and support initiating a comprehensive psychoeducational intervention earlier in the course of illness.     

Erste klinische Erfahrungen mit Lacosamid

Lacosamide (Vimpat®) was labelled for add-on treatment of patients with localization-related epilepsies from age 16 years on in September 2008. Immediately after labelling we started add-on lacosamide in 35 adult patients with difficult-to-treat localization-related epilepsies. In all patients the target maintenance daily dosage was 300 mg, which is not yet reached in eleven cases. In four cases we increased the dose beyond 300 mg, the highest up-to-date dose is 500 mg. First experiences show a satisfying tolerability without relevant titration problems. Only one patient discontinued lacosamide at a dosage of 200 mg because of an increase of seizures. However, due to the high spontaneous fluctuation rate of seizures in this patient a clear causal relationship cannot be claimed. Corresponding with the pivotal clinical trials prior to labelling dizziness was the leading adverse event and mainly occurred at a dose of 300 mg. In almost every case it could be prevented by t.i.d. dosing. The observation period is too short to judge the efficacy of lacosamide. Promising effects during titration were apparent in three seizure-free patients and five responders with a reduction of the baseline seizure frequency by at least 50% during a maintenance period of four to five weeks.     

Intra-articular Botulinum Toxin Type A: A new approach to treat arthritis joint pain

There is a growing need for novel treatments of refractory arthritis joint pain as the aging population is expanding with many patients who are unable to undergo joint replacement surgery. We are studying the efficacy and safety of intra-articular injection of Botulinum Toxin Type A (IA-BoNT/A) into joints with arthritis pain. In several small open label studies, initial effects for IA-BoNT/A were encouraging because two thirds of the patients had more than 50% reduction in joint pain severity that was associated with a significant improvement in function. Importantly no serious adverse effects of IA-BoN/A were noted. Based on these initial results, we have completed two pilot randomized controlled trials in painful shoulder joints and painful knee joints. In the shoulder study, IA-BoNT/A produced a significant decrease in shoulder pain severity at one month (6.8-4.4 on VAS, p = .002) that was also significantly better than the non-significant change after IA-Saline placebo (1.6 unit difference favoring IA-BoNT/A, p = .014). In the knee study IA-BoNT/A produced a significant 48% decrease in McGill Total Pain Score at one month (p = .01 1) that was still significant at 3 mo after injection (p = .002). There was a strong placebo response in one third of those but the decrease in pain severity was not significant. We are currently conducting a RCT of IA-BoNT/A for painful prosthetic knee joints. Based on these initial studies of IA-BoNT/A we have gone ‘back to the bench’ to standardize a menu of pain behaviors for mice with acute inflammatory arthritis pain and chronic inflammatory arthritis pain. IA-BoNT/A significantly reduced arthritis joint tenderness (evoked pain score) in acute and chronic inflammatory arthritis and normalized impaired spontaneous wheel running in mice with chronic inflammatory arthritis but not in those with acute inflammatory arthritis. With these models of arthritis and pain behavior methods we will be able to screen potential intra-articular analgesics, define dose response curves and injection schedule, and study the relationships of articular pain and loss of function.     

Basolateral amygdaloid multi-unit neuronal correlates of discriminative avoidance learning in rabbits

Basolateral (BL) amygdaloid multi-unit activity was recorded as male albino rabbits learned to avoid a foot-shock unconditioned stimulus (US) by stepping in an activity wheel to an acoustic (pure tone) warning stimulus (CS+). A second tone (CS−) of different auditory frequency than the CS+ was presented in an irregular order on half of the conditioning trials but was never followed by the US. BL amygdaloid neurons developed, in the first session of conditioning, enhanced CS-elicited discharges relative to discharges recorded during pretraining with tones and noncontingent US presentations (excitatory plasticity), and greater discharges to the CS+ than to the CS− (discriminative plasticity). The discriminative plasticity attained maximal magnitude as the rabbits reached the asymptote of behavioral discrimination, and persisted during post-asymptotic training. Peak excitatory plasticity occurred in the session of the first significant behavioral discrimination and decline during the asymptotic and post-asymptotic stages of training. Similar patterns of excitatory and discriminative plasticity in structures directly interconnected with the BL nucleus (anterior cingulate cortex; medial dorsal thalamic nucleus) and effects of lesions suggest that the neurons in these areas participate in a circuit involved in mediation of avoidance learning.     

Estimation of choroid perfusion by colour Doppler imaging vs. other methods

Ocular haemodynamics play a prominent role in several ocular diseases. Recently, new methods for the determination of ocular perfusion were developed. Colour Doppler imaging (CDI) of orbital vessels has come up in the past decade and was shown to be useful in ophthalmological diagnostics. Little is known about measurement of choroid perfusion by CDI in comparison with other methods. Therefore, 49 eyes were examined with CDI, laser Doppler flowmetry (LDF) and the method of Langham (LOBF). Correlations between the methods were identified by the Spearman correlation coefficient (r). LDF readings correlated with time-averaged mean velocity assessed by CDI in the long posterior ciliary artery (r = 0.47; p = 0.039; n = 20), but not in the short posterior ciliary artery. LOBF measurements correlated with pulsatility index (PI) of CDI in short (r = 0.50; p = 0.005; n = 30) and long posterior ciliary arteries (r = 0.41; p = 0.024; n = 30). Methods strengthened each other by partial correlation. The study demonstrates that CDI allows a more detailed insight into ocular perfusion.     

Quality of care for patients diagnosed with diabetes at screening

OBJECTIVE: Screening for diabetes has the potential to be an effective intervention, especially if patients have intensive treatment of their newly diagnosed diabetes and comorbid hypertension. We wished to determine the process and quality of diabetes care for patients diagnosed with diabetes by systematic screening. RESEARCH DESIGN AND METHODS: A total of 1,253 users of the Durham Veterans Affairs Medical Center aged 45-64 years who did not report having diabetes were screened for diabetes with an HbA(1c) test. All subjects with an HbA(1c) level > or =6.0% were invited for follow-up blood pressure and fasting plasma glucose (FPG) measurements. A case of unrecognized diabetes was defined as HbA(1c) > or =7.0% or FPG > or =126 mg/dl. For each of the 56 patients for whom we made a new diagnosis of diabetes, we notified the patient's primary care provider of this diagnosis. One year after diagnosis, we reviewed these patients' medical records for traditional diabetes performance measures as well as blood pressure. Follow-up blood pressure was also ascertained from medical record review for all subjects with HbA(1c) > or =6.0% who did not have diabetes. We compared blood pressure changes between patients with and without diabetes. RESULTS: Among patients diagnosed with diabetes at screening, 34 of 53 (64%) had evidence of diet or medical treatment for their diabetes, 42 of 53 (79%) had HbA(1c) measured within the year after diagnosis, 32 of 53 (60%) had cholesterol measured, 25 of 53 (47%) received foot examinations, 29 of 53 (55%) had eye examinations performed by an eye specialist, and 16 of 53 (30%) had any measure of urine protein. The mean blood pressure decline over the year after diagnosis for patients with diabetes was 2.3 mmHg; this decline was similar to that found for 183 patients in the study without diabetes (change in blood pressure, -3.6 mmHg). At baseline, 48% of patients with diabetes had blood pressure <140/90, compared with 40% of patients without diabetes; 1 year later, the same 48% of patients with diabetes had blood pressure <140/90, compared with 56% of patients without diabetes (P = 0.31 for comparing the change in percent in control between groups). CONCLUSIONS: Patients with diabetes diagnosed at screening achieve less tight blood pressure control than similar patients without diabetes. Primary care providers do not appear to manage diabetes diagnosed at screening as intensively as long-standing diabetes and do not improve the management of hypertension given the new diagnosis of diabetes.     

RANKL/RANK/OPG cytokine receptor system: mRNA expression pattern in BPH,primary and metastatic prostate cancer disease

Background

The cytokine system RANKL (receptor activator of NF-κB ligand), its receptor RANK and the antagonist OPG (osteoprotegerin) play a critical role in bone turnover. Our investigation was conducted to describe the gene expression at primary tumour site in prostate cancer patients and correlate the results with Gleason Score and PSA level.

Methods

Seventy-one samples were obtained from prostate cancer patients at the time of radical prostatectomy and palliative prostate resection (n = 71). Patients with benign prostate hyperplasia served as controls (n = 60). We performed real-time RT-PCR after microdissection of the samples.

Results

The mRNA expression of RANK was highest in tumour tissue from patients with bone metastases (p < 0.001) as compared to BPH or locally confined tumours, also shown in clinical subgroups distinguished by Gleason Score (< 7 or ≥ 7, p = 0.028) or PSA level (< 10 or ≥ 10 µg/l, p = 0.004). RANKL and OPG mRNA expression was higher in tumour tissue from patients with metastatic compared to local disease. The RANKL/OPG ratio was low in normal prostate tissue and high tumours with bone metastases (p < 0.05). Expression of all three cytokines was high in BPH tissue but did not exceed as much as in the tumour tissue.

Conclusion

We demonstrated that RANK, RANKL and OPG are directly expressed by prostate cancer cells at the primary tumour site and showed a clear correlation with Gleason Score, serum PSA level and advanced disease. In BPH, mRNA expression is also detectable, but RANK expression does not exceed as much as compared to tumour tissue.

     

Signal transducer of inflammation gp130 modulates atherosclerosis in mice and man

Liver-derived acute phase proteins (APPs) emerged as powerful predictors of cardiovascular disease and cardiovascular events, but their functional role in atherosclerosis remains enigmatic. We report that the gp130 receptor, which is a key component of the inflammatory signaling pathway within hepatocytes, influences the risk of atherosclerosis in a hepatocyte-specific gp130 knockout. Mice on an atherosclerosis-prone genetic background exhibit less aortic atherosclerosis (P < 0.05) with decreased plaque macrophages (P < 0.01). Translating these findings into humans, we show that genetic variation within the human gp130 homologue, interleukin 6 signal transducer (IL6ST), is significantly associated with coronary artery disease (CAD; P < 0.05). We further show a significant association of atherosclerotic disease at the ostium of the coronary arteries (P < 0.005) as a clinically important and heritable subphenotype in a large sample of families with myocardial infarction (MI) and a second independent population-based cohort. Our results reveal a central role of a hepatocyte-specific, gp130-dependent acute phase reaction for plaque development in a murine model of atherosclerosis, and further implicate IL6ST as a genetic susceptibility factor for CAD and MI in humans. Thus, the acute phase reaction should be considered an important target for future drug development in the management of CAD.