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Cannabis is widely used as a self-management strategy by patients with a wide range of symptoms and diseases including chronic non-cancer pain. The safety of cannabis use for medical purposes has not been systematically evaluated. We conducted a prospective cohort study to describe safety issues among individuals with chronic non-cancer pain. A standardized herbal cannabis product (12.5% tetrahydrocannabinol) was dispensed to eligible individuals for a 1-year period; controls were individuals with chronic pain from the same clinics who were not cannabis users. The primary outcome consisted of serious adverse events and non-serious adverse events. Secondary safety outcomes included pulmonary and neurocognitive function and standard hematology, biochemistry, renal, liver, and endocrine function. Secondary efficacy parameters included pain and other symptoms, mood, and quality of life. Two hundred and fifteen individuals with chronic pain were recruited to the cannabis group (141 current users and 58 ex-users) and 216 controls (chronic pain but no current cannabis use) from 7 clinics across Canada. The median daily cannabis dose was 2.5 g/d. There was no difference in risk of serious adverse events (adjusted incidence rate ratio = 1.08, 95% confidence interval = .57–2.04) between groups. Medical cannabis users were at increased risk of non-serious adverse events (adjusted incidence rate ratio = 1.73, 95% confidence interval = 1.41–2.13); most were mild to moderate. There were no differences in secondary safety assessments. Quality-controlled herbal cannabis, when used by patients with experience of cannabis use as part of a monitored treatment program over 1 year, appears to have a reasonable safety profile. Longer-term monitoring for functional outcomes is needed. Study registration The study was registered with www.controlled-trials.com (ISRCTN19449752). Perspective This study evaluated the safety of cannabis use by patients with chronic pain over 1 year. The study found that there was a higher rate of adverse events among cannabis users compared with controls but not for serious adverse events at an average dose of 2.5 g herbal cannabis per day.

This report presents a review of the evidence associated with setting and monitoring safe nurse staffing levels.\ud It also includes analysis of findings related to developing a better understanding of the availability and accessibility of nurse staffing data in medical and surgical wards in Wales.\ud \ud The review of evidence on safe nurse staffing levels includes, for example, nurse-to-patient ratios and skill mix, the role played by nurse staffing levels in influencing patient safety, unintended consequences of mandatory nurse staffing levels and the use of staffing level tools.\ud \ud Availability and accessibility of relevant data focuses on the Electronic Staff Record (ESR), public availability of Welsh NHS staff data, data quality in the ESR database system and possible other sources of data. In addition, a data acquisition exercise with Local Health Boards is outlined, setting out methods, data quality, findings from an initial analysis of the data returned and lessons for future practice.

Translation initiation factor eukaryotic translation initiation factor 4E (eIF4E) plays a key role in regulation of cellular proliferation. Its effects on the m7GpppN mRNA cap are critical because overexpression of eIF4E transforms cells, and eIF4E function is rate-limiting for G1 passage. Although we identified eIF4E as a c-Myc target, little else is known about its transcriptional regulation. Previously, we described an element at position −25 (TTACCCCCCCTT) that was critical for eIF4E promoter function. Here we report that this sequence (named 4EBE, for eIF4E basal element) functions as a basal promoter element that binds hnRNP K. The 4EBE is sufficient to replace TATA sequences in a heterologous reporter construct. Interactions between 4EBE and upstream activator sites are position, distance, and sequence dependent. Using DNA affinity chromatography, we identified hnRNP K as a 4EBE-binding protein. Chromatin immunoprecipitation, siRNA interference, and hnRNP K overexpression demonstrate that hnRNP K can regulate eIF4E mRNA. Moreover, hnRNP K increased translation initiation, increased cell division, and promoted neoplastic transformation in an eIF4E-dependent manner. hnRNP K binds the TATA-binding protein, explaining how the 4EBE might replace TATA in the eIF4E promoter. hnRNP K is an unusually diverse regulator of multiple steps in growth regulation because it also directly regulates c-myc transcription, mRNA export, splicing, and translation initiation.

Ultraviolet A radiation induces oxidative stress and cell damage. The purpose of this investigation was to examine whether ultraviolet A-induced cell injury was amplified by the presence of a non-ultraviolet A absorbing molecule capable of generating free radicals. Benzoyl peroxide was used as a lipid soluble potential radical-generating agent. Plasma membrane permeability assessed by trypan blue uptake was used to measure cell damage in murine leukemia L1210 cells. Cells were irradiated with a pulsed Nd/YAG laser at 355 nm using 0-160 J per cm2. The ratio of the fluence-response slope in the presence of 40 microM benzoyl peroxide to that of irradiated controls was 4.3 +/- 2.6. Benzoyl peroxide alone or benzoyl peroxide added after irradiation did not cause increased trypan blue uptake. The ratio of the fluence-response slopes in the presence of 40 microM benzoyl peroxide to that of irradiated controls was 4.7 +/- 1.4 when cells were irradiated (0-43 J per cm2) with a xenon lamp, filtered to remove wavelengths320 nm. The increased trypan blue uptake in 355 nm-irradiated cells in the presence of benzoyl peroxide was inhibited in a concentration-dependent manner by butylated hydroxytoluene, vitamin E, and trolox, a water-soluble vitamin E derivative. Lipid oxidation, assessed as thiobarbituric acid reactive substances, was significantly increased in samples irradiated with ultraviolet A in the presence of benzoyl peroxide at fluences34 J per cm2. The increased trypan blue uptake and thiobarbituric acid reactive substances were inhibited by butylated hydroxytoluene. These results suggest that agents not absorbing ultraviolet A radiation may enhance ultraviolet A-initiated oxidative stress in cells.

Eighteen patients (3 men and 15 women; mean age 63 years) with right-sided tumors were evaluated by both transthoracic and transesophageal echocardiography from 1989 to 1996. The indications for echocardiographic studies included evaluation for a presumed mass and further evaluation of ventricular function and valvular function. Fifteen patients had right atrial tumors. These included 5 hypernephromas, 4 myxomas, 2 angiosarcomas, 1 lipoma, 1 cavernous hemangioma, 1 hepatoma, and 1 chondrosarcoma. Three patients had right ventricular (RV) tumors: 1 metastatic olfactory neuroblastoma, a leiomyosarcoma, a chondrosarcoma, and a fourth patient had infiltration of the RV free wall of unknown etiology. Biopsy of either right atrial or RV masses was performed with transesophageal echocardiographic guidance in 2 patients, and allowed histologic diagnosis before surgical resection. These findings indicate that tumors are more often found in the right atrium than in the right ventricle, and females predominate. Most tumors arising within the right atrium are benign, whereas those extending into the right atrium from outside are malignant. RV tumors are rarely encountered; when present, they are likely to be malignant.

The efficiency and selectivity of photosensitized damage to membrane functions may be influenced strongly by the identity of the initial reactive species formed by the photosensitizer. To test this possibility, a photosensitizer, rose bengal (RB), was used that resides in the plasma membrane and which generates singlet molecular oxygen (1O2∗) upon excitation with visible light, and radicals plus 1O2∗ upon excitation with UV radiation. With this approach, 1O2∗ and radicals are formed at the same locations in the plasma membrane. The response of three plasma membrane functions, namely, proline transport, membrane potential, and membrane impermeability to charged dye molecules, was assessed. The efficiencies of the responses in the presence and absence of oxygen were compared per photon absorbed by RB at two wavelengths, 355 nm (UV excitation) and 532 nm (visible excitation). The efficiency of oxygen removal before irradiation was assessed by measuring the RB triplet lifetime. The three membrane functions were inhibited more efficiently at 355 nm than at 532 nm in the presence of oxygen indicating that the radicals are more effective at initiating damage to membrane components than 1O2∗. The ratio of photosensitized effects at the two wavelengths in the presence of oxygen was the same for two membrane functions but not for the third suggesting that 1O2∗ and radicals initiate a common mechanistic pathway for damage to some membrane functions but not to others. Removing oxygen reduced the efficiency of 355 nm-induced photosensitization by factors of 1.4 to 7. The sensitivity of the three membrane functions to 1O2∗-initiated damage varied over a factor of 50 whereas radical initiated damage only varied by a factor of 15. In summary, these results indicate that radicals and 1O2∗ formed at the same locations in the plasma membrane vary in their efficiency and specificity for membrane damage but may, in some cases, operate by a common secondary damage mechanism in the presence of oxygen.

Spontaneous rupture of the aorta due to ruptured atherosclerotic plaque is extremely rare. Despite the high prevalence of atherosclerosis, only four cases have been reported to have been identified and treated successfully; the remainder were diagnosed postmortem. We report a surviving case of pericardial tamponade due to highly localised aortic atherosclerotic plaque rupture.

Two membrane-photosensitizing dyes were used to investigate whether selected sites in the plasma membrane vary in their sensitivity to damage by singlet oxygen (1O2*) and, if so, what factors are responsible for the variation. The relative ability of Rose bengal (RB) and merocyanine 540 (MC540), both of which localize in the plasma membrane and produce 1O2*, to photosensitize five plasma membrane functions in P388D1 cells was evaluated. The five membrane functions assessed were: plasma membrane potential, proline transport, facilitated glucose diffusion, 5'-nucleotidase activity, and dye exclusion. Photosensitization efficiency by RB varied by a factor of 188 for these membrane functions, whereas for MC540 a range of only 24 was found. RB was a more efficient photosensitizer than MC540 but the relative efficiencies varied with the membrane function. The wide range of P50 values for RB suggests that it binds selectively to membrane sites where it causes damage with high efficiency; possibly a non-1O2* mechanism is involved. In contrast, MC540 photosensitized the three membrane functions involving integral membrane proteins about equally suggesting that differences are due to small variations in the distribution of MC540 in the plasma membrane and/or variations in the inherent reactivity of the membrane targets with 1O2*. The results indicate that the lability of membrane sites to photosensitization depends both on their inherent reactivity with 1O2* and the relative location of specific protein and dye molecules.

Yin Yang 1 (YY1) is a critical transcription factor controlling cell proliferation, development and DNA damage responses. Retrotranspositions have independently generated additional YY family members in multiple species. Although Drosophila YY1 [pleiohomeotic (Pho)] and its homolog [pleiohomeotic-like (Phol)] redundantly control homeotic gene expression, the regulatory contributions of YY1-homologs have not yet been examined in other species. Indeed, targets for the mammalian YY1 homolog YY2 are completely unknown. Using gene set enrichment analysis, we found that lentiviral constructs containing short hairpin loop inhibitory RNAs for human YY1 (shYY1) and its homolog YY2 (shYY2) caused significant changes in both shared and distinguishable gene sets in human cells. Ribosomal protein genes were the most significant gene set upregulated by both shYY1 and shYY2, although combined shYY1/2 knock downs were not additive. In contrast, shYY2 reversed the anti-proliferative effects of shYY1, and shYY2 particularly altered UV damage response, platelet-specific and mitochondrial function genes. We found that decreases in YY1 or YY2 caused inverse changes in UV sensitivity, and that their combined loss reversed their respective individual effects. Our studies show that human YY2 is not redundant to YY1, and YY2 is a significant regulator of genes previously identified as uniquely responding to YY1.

Objective -To examine the safety and efficacy of alprazolam as an outpatient detoxification agent. Mehtod - Two-year, prospective, uncontrolled study of detoxification from alcohol employing alprazolam in a North Wicklow day centre. The HAD scale was used to measure emotional change. Results -Detoxification was completed in 26 cases. Adverse effects were mild or absent. Significant changes were recorded in both HAD scale scores. Client and staff satisfaction ratings were both high. Conclusions - Alprazolam is a safe and effective detoxification agent in outpatients. The HAD scale provided an objective measure of changes in anxiety and depression in this group of alcoholics. The treated population were older and more often employed than were alcoholics treated in the parent psychiatric hospital.

Question: Which measures of activity limitation on admission to rehabilitation after stroke best predict walking speed at discharge? Design: Prospective observational study. Participants: 120 people with stroke undergoing inpatient rehabilitation. Outcome measures: Predictors were admission walking speed, Timed Up and Go, Motor Assessment Scale, Modified Elderly Mobility Scale, and Functional Independence Measure scores measured on admission to rehabilitation. The outcome of interest was walking speed at discharge from inpatient rehabilitation. Results: Admission walking speed (B 0.47, 95% CI 0.27 to 0.67) and Item 2 of the Motor Assessment Scale, ie, moving from supine lying to sitting over the side of a bed (B 0.05, 95% CI 0.01 to 0.09) predicted walking speed on discharge from rehabilitation. These two predictors explained 36% of the variance in discharge walking speed. Conclusion: Walking speed at discharge from inpatient rehabilitation was best predicted by admission walking speed and Motor Assessment Scale Item 2. [Kuys SS, Bew PG, Lynch MR, Morrison G, Brauer SG (2009) Measures of activity limitation on admission to rehabilitation after stroke predict walking speed at discharge: an observational study. Australian Journal of Physiotherapy 55: 265–268]

PURPOSE: To examine the role of health care professionals in multidisciplinary pain treatment facilities (MPTF) for the treatment of chronic pain across Canada.METHODS: MPTF were defined as clinics that advertised specialized multidisciplinary services for the diagnosis and management of chronic pain, and had staff from a minimum of three different health care disciplines (including at least one medical specialty) available and integrated within the facility. Administrative leaders at eligible MPTF were asked to complete a detailed questionnaire on their infrastructure as well as clinical, research, teaching and administrative activities.RESULTS: A total of 102 MPTF returned the questionnaires. General practitioners, anesthesiologists and physiatrists were the most common types of physicians integrated in the MPTF (56%, 51% and 32%, respectively). Physiotherapists, psychologists and nurses were the most common nonphysician professionals working within these MPTF (75%, 68% and 57%, respectively), but 33% to 56% of them were part-time staff. Only 77% of the MPTF held regular interdisciplinary meetings to discuss patient management, and 32% were staffed with either a psychologist or psychiatrist. The three most frequent services provided by physiotherapists were patient assessment, individual physiotherapy or exercise, and transcutaneous electrical nerve stimulation. The three most common services provided by psychologists were individual counselling, cognitive behavioural therapy and psychodynamic therapy. The major roles of nurses were patient assessment, assisting in interventional procedures and patient education.CONCLUSION: Different health care professionals play a variety of important roles in MPTF in Canada. However, few of them are involved on a full-time basis and the extent to which pain is assessed and treated in a truly multidisciplinary manner is questionable.

The alpha-aminoboronic acid analog of proline has been synthesized and incorporated into a number of peptides as the COOH-terminal residue. These peptide prolyl boronic acids are potent inhibitors of both the type 1 and type 2 IgA proteinases from Neisseria gonorrhoeae and Hemophilus influenzae, but not of the functionally similar IgA proteinase from Streptococcus sanguis. The best inhibitors synthesized thus far have Ki values in the nanomolar range (4.0 to 60 nM). These results indicate that the N. gonorrhoeae and the H. influenzae enzymes belong to the serine protease family of proteolytic enzymes while that from S. sanguis does not. As a group, the IgA proteinases have been noted for their remarkable specificity; thus, the peptide prolyl boronic acids reported here are the first small synthetic molecules to exhibit a relatively high affinity for the active site of an IgA proteinase and are therefore the first to yield some insight into the active site structure and specificity requirements of these enzymes.

Overexpression of cyclin D1 is associated with many cancers, and its overexpression is especially associated with a poor prognosis in breast cancer. Paradoxically, cyclin D1 is known to enhance radiation sensitivity, a finding that has not yet been therapeutically exploited. Proposed cyclin D1 functions that could be involved in this effect include cyclin-dependent kinase (CDK)–dependent phosphorylation of retinoblastoma gene product (pRb), titration of p21/p27 complexes, and less well-characterized effects on gene expression. In this report, we sought to clarify the functions of cyclin D1 that might contribute to enhanced radiation sensitivity. Breast cancer cells stably overexpressing a cyclin D1 mutant (KE) that cannot interact with its CDK partners to phosphorylate pRb were as radiation sensitive as those expressing wild-type D1. Although cyclin D1 has been proposed to affect radiation sensitivity through interactions with p21, a cyclin D1 mutant defective for p21 interactions also increased radiation sensitivity. Cyclin D1 overexpression is generally confined to hormone receptor–positive breast cancers, wherein standard therapies include both radiation and hormonal therapies. Among several proposed CDK-independent cyclin D1 targets, we have identified heat shock protein B8 (HSPB8) as a target particularly associated with cyclin D1 and ER-positive tumors. We therefore evaluated its potential contribution to radiation sensitivity. Overexpression of HSPB8 markedly increased radiation sensitivity, and HSPB8 small interfering RNA blocked cyclin D1's enhancement of radiation sensitivity. Taken together, our results show that some of cyclin D1's effects on radiation sensitivity are CDK and p21 independent and identify HSPB8 as a candidate CDK-independent cyclin D1 target that can mediate its effects. [Cancer Res 2007;67(22):10774–81]

Brauer SG, Bew PG, Kuys SS, Lynch MR, Morrison G. Prediction of discharge destination after stroke using the Motor Assessment Scale on admission: a prospective, multisite study. Objective To determine if admission functional status, measured with the Motor Assessment Scale (MAS), was predictive of discharge destination to home or residential aged care in patients with stroke undergoing rehabilitation. Design Cohort study. Setting Inpatient rehabilitation units. Participants Adults (N=566) diagnosed with stroke undergoing inpatient physiotherapy at one of 15 units in Australia. Intervention Multidisciplinary rehabilitation. Main Outcome Measure Discharge home versus residential aged care. Results Prestroke residential status, gait ability measured with the MAS (MAS-5), rolling ability (MAS-1), and age were able to correctly predict 99% of patients with stroke discharged home and 33.3% discharged to residential aged care facilities, producing an accuracy of 87.3%. Odds ratios indicate that for every 1-point increase in MAS-5 (gait), subjects were 1.66 times more likely to go home (95% confidence interval [CI], 1.28–2.27; P P Conclusions Two items of the MAS assessed on admission to rehabilitation—gait and rolling—in conjunction with basic demographic information of age and prestroke residential status, were highly predictive of discharge from rehabilitation to home.

Background Pregnancies are increasingly seen in women with a gastric band, but no guidance exists on band management during pregnancy. Although band inflation can prevent excessive gestational weight gain and its associated complications, it might have detrimental effects on fetal growth. We compared maternal and perinatal outcomes according to band management strategy—keeping the band inflated throughout pregnancy versus deflation. Methods Data were collected by means of the UK Obstetric Surveillance System (UKOSS) on all pregnancies in women with a laparoscopic adjustable gastric band, booking in UK maternity units (Nov 1, 2011, to Oct 31, 2012). Maternal and perinatal outcomes were compared according to band management strategy, with women in a control group who had not undergone the procedure and with national data. Multivariable regression analyses were used to adjust for potential confounders. Findings 109 cases were reported (prevalence 1·7 per 10 000 maternities), of whom 42 underwent band deflation and 54 had inflation maintained (remainder unknown). Mean weight gain was higher with deflation than inflation (15·4 kg [95% CI 10·8–20·0] vs 7·6 [3·7–11·5], p=0·047). Some evidence of a higher risk of gestational hypertension with deflation than with inflation was noted (relative risk [RR] 6·86, p=0·07). There was strong evidence of a high risk of gestational hypertension with deflation compared with controls and national data (RR 4·74, p=0·001). Mean birth weight was significantly lower in the inflation group than in the deflation group (3380 g [95% CI 3255–3505] vs 3712 [3572–3851], p=0·002). Infants of women with deflation had a high risk of macrosomia compared with controls (adjusted RR 0·40, p=0·002) and national data (RR 2·04, p=0·01). Interpretation Pregnant women with a laparoscopic adjustable gastric band are high risk; the monitoring of both fetal and maternal wellbeing is essential. Maintainance of band inflation during pregnancy reduces gestational weight gain and associated complications, but affects fetal growth. Therefore, maintainance of band inflation throughout pregnancy cannot be recommended. However, inflation for part of the pregnancy might improve some maternal outcomes. Further studies are needed to define the optimum timing of band adjustment. Funding Bristol Bariatric Pregnancy Research Hub.

Despite numerous advances in the recognition, assessment, and management of pain in neonates over the past two decades, there has been limited improvement in the knowledge base regarding parental responses to their infant's pain. This study examined parents' views of their experiences observing and coping with their infant's pain in the neonatal intensive care unit (NICU). Twelve participants were recruited using purposive sampling from two groups: (a) parents who had infants currently receiving care in the NICU (n=6); and (b) parents whose infants had been discharged from the NICU and were enrolled in the outpatient follow-up clinic at each hospital (n=6). An exploratory, semi-structured format was used to interview parents individually (n=5) or in focus groups (n=7) regarding their infant's clinical course, infant pain experiences, and the parenting experience during and after the NICU stay. Thematic content analysis was used to develop conceptual categories. Two broad themes were identified: (a) infant pain as a source of parental distress and (b) relief of parental distress due to infant's pain.

Background Physical inactivity in addition to other influential factors has fuelled the rising level of obesity requiring greater intelligence on motivational cues for engagement in physical activity. The purpose of this study is to assess the value that respondents place on physical activity rather than consume a hypothetical medical tablet by employing Contingent Valuation (CV) and Contingent Behaviour (CB) methods. Results from this study provide constructive insight into the use value and motivations for participating in physical activity rather than avail of a substitute. Methods The data for the study was generated by means of a self administered questionnaire completed by (n=415) respondents in Northern Ireland (NI) from January 2010 to February 2011. We combine actual minutes of physical activity with estimated minutes of physical activity and portray a hypothetical scenario should a medical tablet be available would respondents consume the tablet or do the physical activity. This medical tablet offers the same health benefits of meeting the recommended guidelines of 30 min of physical activity 5 times per week with no side effects. The authors' hypothesise that the time starved population would favour consumption of a medical tablet rather than the allocation of valuable time to engage in physical activity. Physical activity levels are self reported and to ensure certainty of responses a probing question is included to mitigate against biases. Results Preliminary results reveal respondents' prefer to engage in physical activity opposed to the consumption of a medical tablet. The addition of the probing question indicated that respondents prefer to do physical activity for their physical and mental health in addition to a leisure activity aiding relaxation. Preference to participate in physical activity was chosen by 97% of the sample with only 3% of respondents opting for consumption of the medical tablet with respondents' willing to pay £1 for the convenience of consuming a tablet rather than engage in physical activity. Conclusion Our results suggest that respondents' allocate substantial use value to participation in physical activity and the substitution of a time limiting alternative to engagement in physical activity is not highly valued as hypothesised by the authors. Physical activity is valued and our study suggests that individuals engage in physical activity for their physical and mental health and that physical activity is their hobby and relaxing time. These explanations provide valuable insight into the motivations for participating in physical activity and provide intuitive structure and acumen for the future development of physical activity initiatives.

Many cytotoxic agents initiate apoptosis by generating reactive oxidizing species (ROS). The goal of this study was to determine whether apoptosis could be induced by initial reactions of ROS near the plasma membrane. Bovine aorta endothelial cells (BAEC) were illuminated with evanescent wave visible radiation, which has limited penetration into the basal surface of cells, or by trans-radiation. Imaging of fluorescent dyes localizing in the plasma membrane, mitochondria, or nucleus confirmed that evanescent wave radiation excited only dyes in and near the plasma membrane. Singlet oxygen, an ROS generated by photosensitization, has a very short lifetime, ensuring that it oxidizes molecules residing in or very close to the plasma membrane when evanescent wave radiation is used. Cells with condensed nuclei were considered apoptotic and were quantified after treatment with varying doses of light. Annexin V staining without propidium iodide staining confirmed that these cells were apoptotic. The doses required to induce apoptosis using evanescent wave radiation were 10-fold greater than those needed for trans-irradiation. Quantitative analysis of the evanescent wave penetration into cells supports a mechanism in which the singlet oxygen created near the plasma membrane, rather than at intracellular sites, was responsible for initiation of apoptosis.

We reported previously that singlet oxygen, generated by irradiation of rose bengal with visible light, induced apoptosis in human promyelocytic leukemia HL-60 cells. However, the mechanism of apoptosis caused by this reactive oxygen species is unclear. In this study, we demonstrate that singlet oxygen induced caspase-3 activation and Z-DEVD-FMK, a caspase-3 inhibitor, blocked apoptosis induction, while caspase-1 activity was not detectable and the caspase-1 inhibitor Z-YVAD-FMK had a very limited effect on apoptosis. This suggests that the activation of caspase-3 by singlet oxygen is essential for the commitment of cells to undergo apoptosis. Further studies showed that singlet oxygen induced an increase in caspase-8 activity and a reduction in mitochondrial cytochrome c. Time course analysis indicated that the cleavage of caspase-8 precedes that of caspase-3. In addition, blockade of caspase-8 by Z-IETD-FMK inhibited cleavage of pro-caspase-3 and prevented loss of mitochondrial cytochrome c. These results suggest that caspase-8 mediates caspase-3 activation and cytochrome c release during singlet oxygen-induced apoptosis in HL-60 cells.

Closure of the fibrillating left atrial appendage has been recommended during mitral valve operations to help prevent thrombus formation and systemic embolization postoperatively. We report recanalization of the appendage orifice in 6 patients after surgical closure by pursestring suturing at the time of mitral valve replacement. Transesophageal echocardiography demonstrated disruption of the closure line and partial recanalization of the sutured orifice with relatively high velocity flow between the left atrial body and the appendage.

Amphiphysin is an SH3 domain-containing neuronal protein that is highly concentrated in nerve terminals where it interacts via its SH3 domain with dynamin I, a GTPase implicated in synaptic vesicle endocytosis. We show here that the SH3 domain of amphiphysin, but not a mutant SH3 domain, bound with high affinity to a single site in the long proline-rich region of human dynamin I, that this site was distinct from the binding sites for other SH3 domains, and that the mutation of two adjacent amino acids in dynamin I was sufficient to abolish binding. The dynamin I sequence critically required for amphiphysin binding (PSRPNR) fits in the novel SH3 binding consensus identified for the SH3 domain of amphiphysin via a combinatorial peptide library approach: PXRPXR(H)R(H). Our data demonstrate that the long proline-rich stretch present in dynamin I contained multiple SH3 domain binding sites that recognize interacting proteins with high specificity.

Introduction: Safe and high-quality patient care delivery is critically dependent upon the engagement of bedside nurses. The fastest growing group in today’s hospital workforce is the Millennial Generation, a group that has been raised in a world framed by technology. “Gamification” --the applicatio

Cardiac infiltration by lymphoma is a rare finding during life. However, metastatic deposits are frequently found at postmortem in patients with malignant lymphoma. In the past, this may have been due to difficulties in imaging the heart. Today, 2-dimensional echocardiography is a widely used, safe, noninvasive test which allows excellent spatial imaging of cardiac structures. We report a case of extensive primary myocardial and pericardial involvement by malignant lymphoma in which echocardiography was used to document the diagnosis and follow the response to chemotherapy.

Acquired pulmonary artery stenosis is rare. There are two main types, firstly intrinsic disease of the pulmonary valve itself, such as carcinoid heart disease. Secondly, extrinsic compression of the pulmonary artery from a mediastinal structure. We report a case of acquired pulmonary supravalvular stenosis due to extrinsic compression by a carcinoid mediastinal tumor, confirmed by echocardiographic imaging/Doppler interrogation and computerized tomography.

The intensity dependence of the rose bengal (RB)-photosensitized inhibition of red blood cell acetylcholinesterase has been studied experimentally and the results compared to a quantitative excitation/deactivation model of RB photochemistry. Red blood cell membrane suspensions containing 5 microM RB were irradiated with 532 nm, 8 ns laser pulses with energies between 1 and 98.5 mJ. A constant dose (7 J) was delivered to all samples by varying the total number of pulses. At incident energies greater than approximately 4.5 mJ/pulse, the efficiency for photosensitized enzyme inhibition decreased as the energy/pulse increased. The generation of RB triplet state was monitored as a function of laser energy and the triplet-triplet absorption coefficient was determined to be 1.9 x 10(4) M-1 cm-1 at 530 nm. The number of singlet oxygen molecules produced at each intensity was calculated from both the physico-mathematical model and from laser flash photolysis results. The results indicated that the photosensitized inhibition of acetylcholinesterase was exclusively mediated by singlet oxygen, even at the highest laser intensities employed.

TEE played a significant role in the management of 2 patients by defining the extent of cardiac invasion. We believe TEE would be helpful in patients presenting with thoracic tumors believed to be encroaching on cardiac structures, where consideration is being given to surgical resection of the tumor.

The aims of this study were (1) to assess the possibility of predicting allergic reactions to streptokinase (SK) by measuring pretreatment antibody titers and by intradermal skin testing, and (2) to determine if SK is associated with subclinical changes in renal function. Specific anti-SK immunoglobulin G (IgG) and subclass IgG1 were assessed by enzyme-linked immunosorbent sorbent assays, and renal function was assessed by measurement of serum urea and creatinine in 204 patients with acute myocardial infarction. Twenty-six patients had 24-hour proteinuria loss and creatinine clearance assessed at presentation. Median IgG titer at presentation was 6 (range 0 to 10,000), and increased to 60 (range 0 to 18,000; p0.0001) on day 6. Fifteen of 180 patients (8.3%) had minor allergic reactions to SK; the median titer on admission for these patients was 5 (range 0 to 60), identical to those who tolerated SK uneventfully. No change was seen in serum urea or creatinine; for those treated with SK, the median value for proteinuria loss at day 0 was 0.45 g/liter (range 0.1 to 2), and decreased by day 5 to 0.1 g/liter (range 0.1 to 0.8; p = 0.0027). No significant proteinuria was seen in those who did not receive SK. The reactions to SK were minor, and could not be predicted on the basis of IgG titers at presentation. Significant proteinuria was found in the first 24 hours in SK-treated patients, but not in those who did not receive SK, and it resolved by day 5.

A novel oxygen-independent photosensitization mechanism from the upper triplet state (Tn) of rose bengal has been demonstrated by selectively populating Tn by sequential two-color laser excitation. Products formed from Tn inhibit red blood cell acetylcholinesterase and decrease viability of P388D1 mouse macrophage monocyte cells as measured by trypan blue exclusion assay. Laser flash photolysis studies indicate that Tn reacts efficiently, as evidenced by permanent photobleaching of T1 absorption, with chemical yields approaching unit efficiency. This mechanism may have application for oxygen deficient photosensitization under high intensity, pulsed laser irradiation.

The aetiology of left ventricular hypertrophy (LVH) in an athlete is often difficult to identify. We describe a 29-year-old fitness instructor who was referred for investigation of syncope. He gave a history of intensive weight lifting and anabolic steroid use at supra-therapeutic doses for the preceding 6 years. Electrocardiography showed inferolateral repolarisation abnormalities and a transthoracic echocardiogram demonstrated asymmetrical LVH with reduced left ventricular cavity dimensions. There was no left ventricular outflow tract obstruction or systolic motion of the anterior mitral valve leaflet. These findings were confirmed on cardiac magnetic resonance imaging (CMR). The differential diagnosis included athlete's heart, steroid-induced cardiomyopathy and non-obstructive hypertrophic cardiomyopathy. The patient was advised to discontinue both steroid use and intensive training. After 3 years of steroid abstinence but continued training, the syncopal episodes and the ECG abnormalities completely resolved, associated with regression of LVH on echocardiography and CMR.

A 2-fold enhancement in the efficiency of rose bengal-photosensitized inhibition of red cell acetylcholinesterase activity was observed upon excitation of the dye in the ultraviolet (UV) (313 nm) compared to irradiation in the visible (514 or 550 nm). The measurements of efficiency of photosensitized enzyme inhibition were based on the effect produced when the same number of photons are absorbed by rose bengal (RB) at each wavelength. The mechanism for this unexpected enhancement of RB photosensitization upon UV excitation was investigated. The yield of singlet oxygen (O2(1 delta g], detected by time-resolved luminescence at 1270 nm, was independent of excitation wavelength for RB. Radicals were produced upon irradiation of RB at 313 nm but not at 514 nm as detected by bleaching of N,N-dimethylnitrosoaniline (RNO). Irradiation of RB at 313 nm but not at 514 nm appeared to cause homolytic cleavage of carbon-iodine bonds in the dye because iodine radicals, I, detected as I2 were produced with a quantum yield of 0.0041 +/- 0.0005 upon excitation in the UV. Photolysis of I2 in the presence of RNO caused bleaching of the RNO absorption at 440 nm, apparently resulting from reaction of I with RNO. Thus, the enhanced photosensitization upon UV excitation of RB is attributed to formation of I and/or RB. These results indicate that radicals, produced with low relative yield but having high reactivity compared to O2(1 delta g), can contribute to photosensitized enzyme inhibition and may represent an alternative mechanism for photodynamic therapy.