Recurrence of bronchioloalveolar carcinoma in donor lung after lung transplantation: microsatellite analysis demonstrates a recipient origin

Bronchioloalveolar carcinoma is a distinctive subtype of pulmonary adenocarcinoma, without effective therapy, although there have recently been some attempts to use lung transplantation. However, a high post-transplantation local recurrence rate is described with some controversy regarding the possible involved mechanisms, the main possibilities being the lymphatic spread and aerosolization. Presented herein is a case of a bilateral lung transplantation for a bilateral and pneumonic form of non-mucinous bronchioloalveolar carcinoma in a 43-year-old woman. The histological analysis of mediastinal lymph nodes during surgery did not show neoplastic cells. Thirty-five months after transplantation several nodular opacities in donor lungs were detected. Three pulmonary wedge resections were performed showing a non-mucinous bronchioloalveolar carcinoma with the same histological characteristics as the primary. Again, the mediastinal lymph nodes were tumor free. A complete microsatellites molecular analysis was performed to compare the primary and recurrent carcinoma using capillary electrophoresis, showing that the recurrent tumor was generated in a recipient cellular clone. The absence of lymph node metastasis and the molecular evidence of the recipient origin of the neoplasm supports the contamination of the new lungs at the time of implantation as being the reason for the high incidence of recurrence after lung transplantation in this kind of disease.     

Vitamin D food fortification in European countries: the underused potential to prevent cancer deaths

European Journal of Epidemiology - Background: Meta-analyses of randomized controlled trials have shown that vitamin D supplementation reduces cancer mortality by 13%. Vitamin D fortification of...     

Neue Optimierungswege der allgemeinärztlichen Betreuung bei Typ-2-Diabetes

Background

The care of diabetes patients is mostly undertaken by general practitioners. In order to achieve sufficient control of blood sugar levels and blood pressure in patients and thus to avoid complications and secondary diseases, a patient-centered disease management and support of patient self-management are essential. These functions can be partially delegated.

Aim

The DIANA study is an epidemiological physician-based prospective cohort study on new approaches for optimization of general practitioner care. The objectives were to investigate the current status of diabetes care as well as the consequences of a patient-centered treatment approach on the course of diabetes. Furthermore, the effectiveness of a supportive telephone counseling service over 12 months by trained medical practice personnel was investigated.

Material and methods

The DIANA study consists of a basic survey and an interventional study. A total of 38 general medical practices with 1,146 patients diagnosed with type 2 diabetes were included. For the basic survey standardized questionnaires were completed by the patients and their physicians. Furthermore, blood samples were taken from patients for determination of HbA1c levels in a certified laboratory. Patients with HbA1c levels >?7.5?% in the basic survey were eligible for inclusion in the interventional study. In this subpopulation of 204 patients the effectiveness of an intervention with telephone support by trained personnel from the medical practices in the study was investigated. The patients who agreed to participate were randomized to either the intervention group or the control group. The control group received usual care.

Results

Mean HbA1c was 6.9?% in this sample and thus within the target corridor of the new German clinical practice guidelines on type 2 diabetes of 6.5–7.5?%. Nevertheless, about one fifth of the patients’ values were above the corridor and thus in a dissatisfactory zone. In addition, participating patients had considerable comorbidities, such as hypertension, coronary heart disease, cardiac insufficiency, and depression. Another problem was medication adherence among patients. Self-reported medication adherence was associated with poor glycemic control, especially in men. Young, employed and unmarried patients and those with depression symptoms were particularly at risk. The intervention had only limited effects. The primary outcome HbA1c decreased likewise in both groups. A decrease of systolic blood pressure was observed in the intervention group, but which was not sustained after the end of the intervention. It was only after the end of the intervention that health-related quality of life improved in the intervention group.

Conclusion

There is a large problem group of diabetes patients with an unsatisfactory metabolic situation. General practitioners should concentrate on these patients and be aware that younger, employed and single as well as depressive patients are particularly affected. A long-term accompaniment by trained personnel could be useful.     

Software de monitorización de ventilación mecánica domiciliaria: ¿medir más o medir mejor?

In recent years, there has been an increasing interest in knowing the consequences of the patient-ventilator interaction in non-invasive mechanical ventilation. Therefore, several ventilator manufacturers have incorporated into their devices the possibility to monitor ventilation on-line and download the data stored in their internal memories. However, there is not a consensus as to how these data should be presented, and said devices have still not been sufficiently validated to be used systematically in clinical practice. The objective of the present study is to develop a critical, argumentative analysis of the technical characteristics for determining the monitor variables used in the different software programs incorporated in commercial ventilators. Likewise, the study contemplates the presentation of the measurements on the screen display, emphasizing the advantages and defects of each one and analyzing their behavior in common clinical practice situations, such as changes in the interface or the presence of accidental leaks. In addition, solution mechanisms are proposed for establishing future directives for the parameters that are important for clinicians, as well as the manner for providing and interpreting said information.     

Rescuing prefrontal cAMP-CREB pathway reverses working memory deficits during withdrawal from prolonged alcohol exposure

Both human and animal studies indicate that alcohol withdrawal following chronic alcohol consumption (CAC) impairs many of the cognitive functions which rely on the prefrontal cortex (PFC). A candidate signaling cascade contributing to memory deficits during alcohol withdrawal is the protein kinase A (PKA)/cAMP-responsive element binding (CREB) cascade, although the role of PKA/CREB cascade in behavioral and molecular changes during sustained withdrawal period remains largely unknown. We demonstrated that 1 week (1W) or 6 weeks (6W) withdrawal after 6-month CAC impairs working memory (WM) in a T-maze spontaneous alternation task and reduces phosphorylated CREB (pCREB) in the PFC but not the dorsal CA1 region (dCA1) of the hippocampus compared with CAC and water conditions. In contrast, both CAC-unimpaired and withdrawn-impaired mice exhibited decreased pCREB in dCA1 as well as reduced histone H4 acetylation in PFC and dCA1, compared with water controls. Next, we showed that enhancing CREB activity through rolipram administration prior to testing improved WM performance in withdrawn mice but impaired WM function in water mice. In addition, WM improvement correlates positively with increased pCREB level selectively in the PFC of withdrawn mice. Results further indicate that direct infusion of the PKA activator (Sp-cAMPS) into the PFC significantly improves or impairs, respectively, WM performance in withdrawn and water animals. In contrast, Sp-cAMPS had no effect on WM when infused into the dCA1. Collectively, these results provide strong support that dysregulation of PKA/CREB-dependent processes in prefrontal neurons is a critical molecular signature underlying cognitive decline during alcohol withdrawal.     

Dynamic interplays between memory systems depend on practice: the hippocampus is not always the first to provide solution

Previous studies showed that the optimization of behavioral performance through extended training depends on a switch from hippocampus-based memory to striatum-based habit. Here we investigate whether the amount of training within one learning session influences the retention of memory for hippocampal versus striatal strategies. Mice were trained to search for a submerged cue-marked platform which remained in the same spatial location in the water-maze for each of three training regimens (4, 12 or 22 trials). Subsequently, they were either tested for retention of memory 1 h or 24 h later on a probe test or killed at different time points over a 7-h period to determine the kinetic of cAMP response element binding protein (CREB) phosphorylation in both memory systems. During the probe test mice had to choose between a submerged platform located in the same position as during the acquisition phase (spatial solution) and a platform marked by the cue but located in the opposite quadrant of the pool (cue-guided solution). Results showed that the animals first preferred the cue-marked platform, which represents a strategy that was selectively impaired by lesions of the dorsolateral caudate-putamen. With further practice, or context pre-exposure, animals transiently favored the hippocampus-dependent place solution but finally, both strategies became interchangeable and insensitive to either lesion. CREB phosphorylation increased in both memory systems following acquisition but training-dependent changes selectively occurred in the hippocampus wherein biphasic activation was initiated by the four-trial training and blocked by training for 22 trials. These findings indicate that learning in one session consists of three acquisition stages with parallel engagement of multiple memory systems at the beginning of learning. They suggest, however, that, in a later phase, dynamic interplays promote the use of the most adapted brain system depending on practice and this is accompanied by specific patterns of CREB phosphorylation in the hippocampus.