Similar left and right ventricular sarcomere structure after support with a left ventricular assist device suggests the utility of right ventricular biopsies to monitor left ventricular reverse remodeling

BACKGROUND: To evaluate whether the morphology of the contractile filaments in cardiomyocytes of patients with end-stage heart failure, treated with a left ventricular assist device (LVAD), is identical in the left- and right ventricle (LV, RV) and in the interventricular septum (IVS) and can be monitored by biopsies taken with a bioptome. The application of an LVAD as a bridge to recovery of cardiac function requires monitoring of myocyte recovery. The use of RV biopsies for this purpose might be feasible, if morphologic findings in the RV coincide with those in the LV. METHODS AND RESULTS: At the time of heart transplantation, myocardial biopsies of LV, RV and IVS from 13 patients after LVAD support were compared using immunohistochemistry with monoclonal antibodies against contractile proteins. Additionally, in five of these patients, small biopsies obtained with a diagnostic bioptome were compared with large transmural biopsies of the same region. Hemodynamic monitoring was performed when the patients were fully recovered from the implantation, to rule out persistent RV failure. The staining pattern of actin, myosin, tropomyosin, troponin T and C was identical in the biopsies of LV, RV and IVS. Small biopsies taken with a bioptome appeared to be representative for the larger biopsies. Hemodynamic monitoring showed absence of RV failure in our study group. CONCLUSION: In the absence of RV failure, morphology of the contractile myofilaments after LVAD support for 215+/-143 days is identical in LV, RV and IVS. This may allow monitoring of the possible occurrence of LV reverse remodeling by RV biopsies.     

The relevance of team characteristics and team directed strategies in the implementation of nursing innovations: A literature review

BackgroundImplementation of innovations is a complex and intensive procedure in which different strategies can be successful. In nursing, strategies often focus on intrinsic motivation, competencies and attitudes of individual nurses while ignoring the social context. Since nurses often work in teams, identifying relevant team characteristics and successful team directed strategies may contribute to the implementation of innovations. The literature was searched for evidence.MethodsA literature review was performed including key words related to nursing teams, innovations, team characteristics and team-directed strategies. On-line databases were searched (MEDLINE, CINAHL, PsycINFO, ERIC database and Cochrane reviews CENTRAL). The journal Quality and Safety in Healthcare (QSHC) was hand searched. Methodological quality was assessed.ResultsInitially, 323 titles were found. Screening of titles and abstracts and full texts resulted in nine articles meeting the inclusion criteria. The methodological quality of the studies was generally low. The innovations included different types of practices. Fifteen different team characteristics were labeled according to six features of successful teams.Twenty-one different team-directed strategies were identified and inductively categorized.ConclusionFew studies and little evidence were found for the relevance of team characteristics and team directed strategies in the implementation of nursing innovations. Feedback was most frequently used as a strategy. Leadership could be labeled as a team characteristic as well as a team directed strategy. Further research should be of good methodological quality and focusing on patient outcomes and time and costs invested in strategy delivery. This increases scientific knowledge on nursing implementation strategies focusing on leadership.     

A potential role for muscle in glucose homeostasis: in vivo kinetic studies in glycogen storage disease type 1a and fructose-1,6-bisphosphatase deficiency

Background  

A potential role for muscle in glucose homeostasis was recently suggested based on characterization of extrahepatic and extrarenal glucose-6-phosphatase (glucose-6-phosphatase-β). To study the role of extrahepatic tissue in glucose homeostasis during fasting glucose kinetics were studied in two patients with a deficient hepatic and renal glycogenolysis and/or gluconeogenesis.     

Targeting of doxorubicin to the urinary bladder of the rat shows increased cytotoxicity in the bladder urine combined with an absence of renal toxicity

Targeting of anti-tumor drugs to the urinary bladder for the treatment of bladder carcinoma may be useful, since these agents generally have a low degree of urinary excretion and are highly toxic elsewhere in the body. The anti-tumor drug doxorubicin was coupled to the low-molecular weight protein lysozyme via the acid-sensitive cis-aconityl linker. All free amino groups of the lysozyme were used for drug attachment to achieve intact excretion of the doxorubicin-aconityl-lysozyme conjugate into the bladder. In the bladder, the cytotoxic drug should be regenerated through acidification of the urine. First, the doxorubicin-aconityl-lysozyme conjugate was tested in rats for its target specificity and general toxicity. Wistar rats were injected intravenously with 2 mg/kg free doxorubicin or 10 mg/kg lysozyme-conjugated doxorubicin. Total urinary excretion of doxorubicin was about 10 times higher if the drug was coupled to lysozyme (39 +/- 3% versus 4.4 +/- 0.4%). Free doxorubicin had no detectable toxic effects on heart, liver and lung but caused severe renal damage (proteinuria, N-acetylglucosaminidase excretion and glomerulosclerosis). None of the rats injected with doxorubicin-lysozyme conjugate showed such renal toxicity. Second, we tested whether doxorubicin could be released from the conjugate in the bladder through acidification of the urine and if the released doxorubicin could still exert a cytotoxic effect. Doxorubicin-aconityl-lysozyme (2 mg/kg conjugated doxorubicin, i.v.) was administered in rats with acidified urine (pH 6.1 +/- 0.1) and in rats with a high urinary pH (8.2 +/- 0.4). Ten times more doxorubicin was released from the conjugate in the group with acidified urine (15 +/- 7% versus 1.7 +/- 0.1%). In agreement with this, cytotoxicity was also higher in the low pH group (IC50 of 255 +/- 47 nM versus 684 +/- 84 nM doxorubicin). In conclusion, a specific delivery of doxorubicin to the urinary bladder combined with a reduced toxicity of doxorubicin in the kidneys can be achieved by coupling this anti-tumor drug to the low-molecular weight protein lysozyme via an acid-labile linker. A release of cytotoxic doxorubicin in the urinary bladder can be achieved by acidification of the urine. This technology, after further optimization, may provide an interesting tool for the treatment of bladder carcinoma.     

The last breath. The decision to ventilate patients with severe chronic obstructive pulmonary disease or not

Three patients, a 74-year-old man and 2 women aged 40 and 58 years, were admitted to the hospital on a number of occasions due to respiratory insufficiency as a result of progressive debilitating COPD. Weaning from mechanical ventilation became increasingly difficult. Therefore, in two patients it was eventually decided not to apply mechanical ventilation again; they died after the next COPD exacerbation. The 40-year-old woman was eligible for a lung transplant and was placed on the waiting list for this procedure. The decision to mechanically ventilate patients with severe COPD and respiratory insufficiency is fraught with therapeutical, emotional and ethical dilemma. Objective criteria indicating a poor outcome in mechanically ventilated patients with severe COPD are: a forced expiratory volume in one second lower than 700 ml, being housebound, advanced age, cardiac comorbidity, and a low serum albumin concentration prior to mechanical ventilation. Since subjective criteria such as the patient's own wishes should also be considered, a policy is advocated in which the consultant pulmonologist regularly evaluates the available data and communicates the feasibility of mechanical ventilation.     

Cognitive dysfunction and chemotherapy: neuropsychological findings in perspective

Currently, the interest in cognitive functioning following chemotherapy is rapidly expanding as is reflected in a growing number of published studies on this topic. Although most studies are indicative of cognitive deficits after chemotherapy, definite conclusions on the role of chemotherapy on cognitive function can often not be drawn due to methodological problems. On the basis of the studies on cognitive functioning after chemotherapy that are conducted in The Netherlands Cancer Institute, the current article describes a number of such methodological topics that obscure straightforward interpretation of neuropsychological findings in toxicity research. Measurement issues that diverge from usual assessment issues encountered in psychosocial oncology will be described, and factors that might play a role in the cause of cognitive impairment will be evaluated. Also, future developments necessary to gain more insight into the prevalence, the pattern, and the impact of cognitive problems following chemotherapy are discussed