Evaluation of urinary myoglobin assay test for myocardial infarction.

Serial determinations of urinary myoglobulin, beta2-microglobulin and albumin, and of serum myoglobin, were performed in twenty-eight consecutive patients admitted to a coronary care unit. Patients with myocardial infarction (MI patients) all had higher serum levels of myoglobin then those with other diagnoses (OBS patients). Myoglobinuria occurred in 80% of MI patients and in half of the OBS patients. The appearance of myoglobin in urine was mainly accounted for by an impaired renal reabsorption of low molecular weight proteins. Measurement of urinary myoglobulin, in contrast to serum myoglobulin, is of little value for the diagnosis of myocardial infarction.     

Preoperative MRI of the Breast (POMB) Influences Primary Treatment in Breast Cancer: A Prospective,Randomized, Multicenter Study

Background

Breast magnetic resonance imaging (MRI) has shown high sensitivity in determining tumor extent, multifocality, and occult contralateral breast cancer. Low specificity, unnecessary mastectomies, and costs are arguments against MRI. The purpose of this study was to determine whether preoperative breast MRI would affect primary surgical management, reduce reexcision/reoperation procedures, and influence the choice of neoadjuvant treatment in patients with newly diagnosed breast cancer.

Methods

This prospective, randomized, multicenter study included 440 breast cancer patients younger than aged 56 years from three, Swedish, large-volume breast units. Patients were randomly allocated on a 1:1 basis to either preoperative staging with breast MRI (n = 220) or no breast MRI (n = 220) (control group). Treatment planning of all patients was discussed at multidisciplinary team conferences.

Results

In patients randomized to the MRI group, who had an observed higher percentage of planned breast-conserving surgery (BCS) compared with the control group, a change from suggested breast conservation to mastectomy occurred in 23 of 153 (15 %) patients. Breast MRI provided additional information in 83 of 220 (38 %) patients, which caused a change in treatment plan in 40 (18 %). The breast reoperation rate was significantly lower in the MRI group: 11 of 220 (5 %) versus 33 of 220 (15 %) in the control group (p < 0.001). The number of mastectomies, axillary reoperations, and the number of patients receiving neoadjuvant chemotherapy after definitive treatment did not differ significantly between the groups.

Conclusions

Preoperative staging with breast MRI in women younger than age 56 years altered the treatment plan in 18 % of the patients. Although a higher MRI-related conversion rate from breast conservation to mastectomy was found, the final numbers of mastectomies did not differ between the two groups. The breast reoperation rate in the MRI group was significantly reduced.     

Ambulatory ST-recording has no additional value to exercise test for identification of severe coronary lesions after an episode of unstable coronary artery disease in men

One month after an episode of unstable coronary artery disease, 95 male patients performed coronary angiography, 48 hours ambulatory ST-recording and also an exercise test. ST-depression occurred in 29.5% during the ST-recording and in 44.2% during the exercise test (p<0.05). In patients with ST-depression at ambulatory monitoring, 79% demonstrated the same finding at the exercise test. A high risk response at the exercise test — defined as either ST-depression in 3 leads, ST-depression in 1–2 leads with a maximal work load below the 60th percentile or a maximal work load below the 30th percentile regardless of the ECG reaction — occurred in 56.8%. Severe coronary lesions — defined as three vessel disease, left main stenosis or proximal left anterior descending artery stenosis as part of two vessel disease — was observed in 46.3%. Patents with a high risk exercise test response and patients with ST-depression during ST-recording had severe coronary lesions in 67% and 64% respectively. However, a high risk exercise test response occurred in 82%, while ST-depression at ambulatory monitoring was observed only in 41% of the patients with severe coronary lesions (p < 0.001). Thus, ambulatory ST-recording one month after an episode of unstable coronary artery disease in men adds no further information to a symptom limited exercise test in order to identify patients with severe coronary lesions.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Structural foundations of optogenetics: Determinants of channelrhodopsin ion selectivity

The structure-guided design of chloride-conducting channelrhodopsins has illuminated mechanisms underlying ion selectivity of this remarkable family of light-activated ion channels. The first generation of chloride-conducting channelrhodopsins, guided in part by development of a structure-informed electrostatic model for pore selectivity, included both the introduction of amino acids with positively charged side chains into the ion conduction pathway and the removal of residues hypothesized to support negatively charged binding sites for cations. Engineered channels indeed became chloride selective, reversing near −65 mV and enabling a new kind of optogenetic inhibition; however, these first-generation chloride-conducting channels displayed small photocurrents and were not tested for optogenetic inhibition of behavior. Here we report the validation and further development of the channelrhodopsin pore model via crystal structure-guided engineering of next-generation light-activated chloride channels (iC++) and a bistable variant (SwiChR++) with net photocurrents increased more than 15-fold under physiological conditions, reversal potential further decreased by another ∼15 mV, inhibition of spiking faithfully tracking chloride gradients and intrinsic cell properties, strong expression in vivo, and the initial microbial opsin channel-inhibitor–based control of freely moving behavior. We further show that inhibition by light-gated chloride channels is mediated mainly by shunting effects, which exert optogenetic control much more efficiently than the hyperpolarization induced by light-activated chloride pumps. The design and functional features of these next-generation chloride-conducting channelrhodopsins provide both chronic and acute timescale tools for reversible optogenetic inhibition, confirm fundamental predictions of the ion selectivity model, and further elucidate electrostatic and steric structure–function relationships of the light-gated pore.Discovery and engineering of the microbial opsin genes not only has stimulated basic science investigation into the structure–function relationships of proteins involved in light-triggered ion flow but also has opened up opportunities for biological investigation (reviewed in ref. 1) via the technique of optogenetics, which involves targeting these genes and corresponding optical stimuli to control activity within specified types of cells within intact and functioning biological systems. For example, optogenetics has been used to identify causally the brain cells and projections involved in behaviors relevant to memory formation, affective states, and motor function, among many other discoveries (2–4). For the channelrhodopsins, an important member of this protein family widely used in optogenetics (5, 6), the light-activated cation-conducting channel pore has been the subject of structural investigation, both because of curiosity regarding the physical properties of its ion conduction and because the creation of inhibitory channels had been sought for optogenetic applications. Converging lines of work recently achieved the latter goal; resolving the high-resolution structure of channelrhodopsin (7) allowed a principled structure-guided approach to engineering for chloride selectivity by testing an electrostatic model for pore function (8, 9). Subsequently, by screening the genome of the Guillardia theta microbe, two naturally occurring light-gated chloride-conducting channelrhodopsins (10) were identified.Because optogenetic control of behavior has not yet been demonstrated with chloride channelrhodopsins, and to test further integrative ideas regarding pore function from structural considerations as shown here, we sought to design and test the next generation of enhanced chloride channels (iC++ and SwiChR++). Along the way, we provide the initial test of the hypothesis that light-activated channels will be more efficient tools than pumps for optogenetic neuronal inhibition at the cellular level, demonstrate the initial utility of light-gated chloride channels in controlling behavior in freely moving animals, and reveal key principles regarding the functional selectivity of light-gated ion channel pores.     

Comparison of treatment and outcomes for patients with acute myocardial infarction in Minneapolis/St. Paul, Minnesota, and Göteborg, Sweden

Background

Treatment of acute myocardial infarction (AMI) is changing, and differences in medical practice are observed within and between countries on the basis of local practice patterns and available technology. These differing approaches provide an opportunity to evaluate medical practice and outcomes at the population level. The primary aim of this study was to compare medical care in patients hospitalized with AMI in 2 large cities in Sweden and the United States. A secondary aim was to compare medical outcomes.

Methods

All resident patients (age range, 30-74 years) hospitalized with AMI in Göteborg, Sweden (1995-1996), and a representative population-based sample of all patients with AMI in Minneapolis/St. Paul, Minn (1995).

Results

Patients with AMI in Göteborg (GB) were older than patients in Minneapolis/St. Paul (MSP), but fewer patients in GB had a prior history of cardiovascular disease. During the AMI admission, coronary angiography, percutaneous coronary angioplasty (PTCA), and coronary artery bypass grafting (CABG) were performed twice as frequently in MSP than in GB. Echocardiogram and exercise testing were more frequently performed in GB. During hospitalization, β-blockers were more frequently prescribed in GB, whereas calcium channel blockers, long- and short-acting nitrates, intravenous nitroglycerine, digitalis, aspirin, oral anticoagulants, heparin, and lidocaine were significantly more common in MSP. Thrombolysis, acute PTCA, ACE inhibitors, and diuretics were similar. Reinfarction was higher in men in GB (4% vs 1%, P <.009) and women in GB (3% vs 1%, P = not significant). On discharge, β-blockers and diuretics were prescribed significantly more often in GB, whereas calcium channel blockers, nitrates, and digitalis were prescribed more often in MSP. Aspirin and ACE inhibitors had similar usage rates. Despite these diagnostic and treatment contrasts, there were no differences in mortality rate at 30 days or after 3 years of follow-up after risk-adjusting for patient baseline differences.

Conclusion

Comparing patients hospitalized with AMI in MSP and GB, we found marked differences in medical care, with invasive strategies more likely to be used in MSP. This may be the result of historical practice patterns, the healthcare system, and healthcare financing differences. Despite these differences, short- or long-term mortality rates were identical.     

A pragmatist approach to the hope discourse in health care research

Hope is a central concept in nursing and other fields of health care. However, there is no consensus about the concept of hope. We argue that seeking consensus is futile given the multifaceted and multidimensional nature of the concept, but instead we encourage in‐depth studies of the assumptions behind talk about hope in specific contexts. Our approach to the ‘science of hope’ is inspired by philosophical pragmatism. We argue that hope is a concept that opens different rooms for action in different contexts and that accordingly, all hope interventions are contextually sensitive. Careful attention to how the relative positions and power of nurses and patients influence what can be inferred from their different ways of talking about hope may make hopeful conversations more meaningful in health care relationships.     

Handheld ECG in analysis of arrhythmia and heart rate variability in children with Fontan circulation

Background

Our aim was to evaluate the intermittent use of a handheld ECG system for detecting silent arrhythmias and cardiac autonomic dysfunction in children with univentricular hearts.

Methods

Twenty-seven patients performed intermittent ECG recordings with handheld devices during a 14-day period. A manual arrhythmia analysis was performed. We analyzed heart rate variability (HRV) using scatter plots of all interbeat intervals (Poincaré plots) from the total observation period. Reference values of HRV indices were determined from Holter-ECGs in 41 healthy children.

Results

One asymptomatic patient had frequent ventricular extra systoles. Another patient had episodes with supraventricular tachycardia (with concomitant palpitations). Seven patients showed reduced HRV.

Conclusions

Asymptomatic arrhythmia was detected in one patient. The proposed method for pooling of intermittent recordings from handheld or similar devices may be used for detection of arrhythmias as well as for cardiac autonomic dysfunction.     

Item Response Model Adaptation for Analyzing Data from Different Versions of Parkinson’s Disease Rating Scales

Pharmaceutical Research - Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel technique delivering drugs into the abdominal cavity as an aerosol under high pressure. It is...