Estimated relation of Doppler echocardiography parameters of diastolic ventricular function and pulmonary capillary pressure in acute ischemia

A close relation between the Doppler-echocardiographic transmitral flow signal (TMF) and the left ventricular filling pressure in patients with coronary heart disease (CHD) was described in several reports. The present study investigated the validity of this relation during an episode of acute ischemia induced by coronary angioplasty (PTCA) by simultaneous recording of TMF and mean pulmonary capillary wedge pressure (PCm). Thirty-nine patients were examined at rest, and 33 of them were further studied during a subsequent PTCA of the left anterior descending artery (n = 22) or the right coronary artery (n = 11). The onset of ischemia was evaluated by electrocardiography. The Doppler-echocardiographic parameters of diastolic ventricular function were correlated with PCm; the closest correlation was obtained for the relation between PCm and the ratio of the early/atrial velocity integral (Ei/Ai: r = 0.59; p less than 0.0001), and between PCm and the relative share of the early diastolic velocity integral (Ei%: r = 0.58; p less than 0.0001). A wide confidence interval of individual values did not allow a calculation of PCm from Ei/Ai. By a semiquantitative approach an elevated PCm could be estimated from Ei/Ai greater than 1.5 with a high sensitivity (86%) and specificity (81%). During PTCA an increase of PCm was observed (start: 10.2 +/- 4.8; end: 15.0 +/- 6.5; p less than 0.0001), while Ei/Ai decreased slightly (start: 1.37 +/- 0.41; end: 1.27 +/- 0.51; p = 0.32). With increasing duration of inflation, the correlation between PCm and Doppler-echocardiographic parameters was attenuated.(ABSTRACT TRUNCATED AT 250 WORDS)     

R wave undersensing caused by an algorithm intended to enhance sensing specificity in an implantable cardioverter defibrillator

This article reports on a case of ventricular undersensing despite normal R wave amplitudes during sinus rhythm in an ICD patient. Undersensing of ventricular signals was noted without any evidence of lead dislocation or variation in signal amplitude. Undersensing was due to an exceptionally small R wave signal width and a feature of the Biotronik sensing algorithm designed to avoid oversensing. This algorithm, intended to enhance the sensing specificity of the device, requires registration of two consecutive points above the maximum programmed sensitivity for a ventricular sense event. After modifying the algorithm to a single point registration undersensing disappeared.     

Angiopoietin 1 inhibits ocular neovascularization and breakdown of the blood-retinal barrier

Several retinal and choroidal diseases are potentially treatable by intraocular delivery of genes whose products may counter or neutralize abnormal gene expression that occurs as part of the diseases. However, prior to considering a transgene, it is necessary to thoroughly investigate the effects of its expression in normal and diseased eyes. An efficient way to do this is to combine tissue-specific promoters with inducible promoter systems in transgenic mice. In this study, we used this approach to evaluate the effects of ectopic expression of angiopoietin-1 (Ang1) in normal eyes and those with ocular neovascularization. Adult mice with induced expression of Ang1 ubiquitously, or specifically in the retina, appeared normal and had no identifiable changes in retinal or choroidal blood vessels or in retinal function as assessed by electroretinography. Increased expression of Ang1 in eyes with severe retinal ischemia or in eyes with rupture of Bruch's membrane significantly suppressed the development of retinal or choroidal neovascularization, respectively. This inhibition of ocular neovascularization is particularly interesting and noteworthy, because overexpression of Ang1 in skin stimulates neovascularization. Ang1 also significantly reduced VEGF-induced retinal vascular permeability. These data suggest that intraocular delivery of ang1 has potential for treatment of ocular neovascularization and macular edema.     

Long-term complication rates in ventricular, single lead VDD, and dual chamber pacing

A higher incidence of pacemaker related complications has been reported in DDD systems as compared to VVI devices. The implantation of single lead VDD pacemakers might reduce the complication rate of physiological pacing in patients with AV block. In a retrospective study, the data records of 1,214 consecutive patients with pacemaker implantation for AV block between 1990 and 2001 (VVI 36.5%, DDD 32.9%, VDD 30.6%) were analyzed. Complications requiring surgical interventions were compared during a follow-up period of 64 +/- 31 months. Operation and fluoroscopic times were longer in DDD pacemaker implantation compared to VDD and VVI devices:58 +/- 23 versus 39 +/- 10 and 37 +/- 13 minutes (P<0.001), 9.2 +/- 5.2 versus 4.1 +/- 2.4 and 3.5 +/- 2.3 minutes, respectively. Differences remained significant after correction for covariates. In a multivariate Cox regression model, the corrected complication hazard of a DDD pacemaker implantation was increased by 3.9 (1.4-11.3) compared to VVI and increased by 2.3 (1.1-4.5) compared to VDD pacing. Higher complication rates in DDD pacing were mainly due to a higher incidence of early reoperation for atrial lead dysfunction, whereas the long-term complication rate was not different from VDD or VVI pacing. Early and long-term complication rates did not differ between VDD and VVI pacemaker systems. In conclusion, operation time and complication rates of physiological pacing are reduced by VDD pacemaker implantation achieving values comparable to VVI pacing. Thus, single lead VDD pacing can be recommended for patients with AV block.     

Withdrawal of cardiac medications and devices

Withdrawal of life-sustaining therapies such as cardiac medications, pacemakers, internal cardioverter defibrillators, and ventricular assist devices occurs in patients with advanced cardiac disease as goals of treatment transition from active to less aggressive. This article defines life-sustaining therapies and describes ethical and legal considerations related to withdrawal of cardiac medications and cardiac devices. Healthcare providers need to anticipate clinical situations in which implantable cardiac devices and medications are no longer desired by patients and/or are no longer medically appropriate. Discussions are important between patients, families, and healthcare providers that focus on each patient's condition, prognosis, advance directives, goals of care, and treatment options. Critical care nurses support each patient and his or her family and work with other members of the healthcare team to achieve a peaceful death.     

Health effects from unintentional occupational exposure to opioids among law enforcement officers: Two case investigations

Recent increases in the rate of drug overdose-related deaths, the emergence of potent opioids such as carfentanil, and media reports of incidents have raised concerns about the potential for work-related exposure to a variety of illicit drugs among law enforcement officers (LEOs), other emergency responders, and other workers in the United States. To characterize the risk associated with unintentional occupational exposure to drugs, we retrospectively investigated two incidents that occurred in 2017 and 2018 where LEOs were exposed to opioid and stimulant drugs and experienced health effects. We interviewed five affected LEOs and others. We reviewed records, including emergency department documentation, incident reports, forensic laboratory results, and when available, body camera footage. Multiple drug types, including opioids and nonopioids, were present at each incident. Potential routes of exposure varied among LEOs and were difficult to characterize with certainty. Health effects were not consistent with severe, life-threatening opioid toxicity, but temporarily precluded affected LEOs from performing their essential job duties. While health risks from occupational exposure to drugs during law enforcement activities cannot currently be fully characterized with certainty, steps to prevent such exposures should be implemented now. The creation and implementation of appropriate controls plus education and training are both important to protecting first responders from these hazardous agents. To more fully characterize potential exposures, timely prospective toxicological evaluation of affected responders is recommended.     

Management of chronic hepatitis B: status and challenges beyond treatment guidelines

Several national and international guidelines have been published in the last years focusing on the problem of how to best treat patients with chronic hepatitis B virus (HBV) infection. Therapy with interferon or nucleos(t)ide analogues has been shown to be most effective in suppressing HBV deoxyribonucleic acid (DNA) levels and preventing fibrosis progression herby also reducing the risk of hepatocellular carcinoma (HCC). However even suppression of viral replication below the limit of detection does not prevent HCC development although fibrosis can be stopped. Thus, improvement of therapeutic strategies and the establishment of more sensitive markers that may help to decide when therapy should be initiated and stopped remain important goals in hepatitis research. The present review discusses several major issues in this respect such as strategies to identify the optimal time point for treatment indication and end of therapy. It also concentrates on questions and queries that have to do with the interpretation of viral parameters like HBsAg quantification, HBV genotypes, and HBeAg, or the characterization of risk patients prone to develop fatal sequel of the HBV infection.     

The Toxicology Investigators Consortium Case Registry—The 2011 Experience

In 2010, the American College of Medical Toxicology established its Case Registry, the Toxicology Investigators Consortium (ToxIC). ToxIC is a prospective registry, which exclusively compiles suspected and confirmed toxic exposure cases cared for at the bedside by medical toxicologists at its participating sites. The Registry aims to fulfill two important gaps in the field: a real-time toxicosurveillance system to identify current poisoning trends and a powerful research tool in toxicology. ToxIC allows extraction of information from medical records making it the most robust multicenter database on chemical toxicities in existence. All cases seen by medical toxicologists at participating institutions were entered in a database. Information characterizing patients entered in 2011 was tabulated. 2010 data was also included so that cumulative total numbers could be described as well. The current report is a summary of the data collected in 2011 in comparison to 2010 entries and also includes cumulative data through December 31st, 2011. During 2011, 28 sites with 49 specific institutions contributed a total of 6,456 cases to the Registry. The total number of cases entered into the registry at the end of 2011 was 10,392. Emergency departments remained the most common source of consultations in 2011, accounting for 53 % of cases. The most common reason for consultation was for pharmaceutical overdoses, which occurred in 48 % of patients, including intentional (37 %) and unintentional (11 %) exposures. The most common classes of agents were sedative–hypnotics (1,492 entries in 23 % of cases), non-opioid analgesics (1,368 cases in 21 % of cases), opioids (17 %), antidepressants (16 %), stimulants/sympathomimetics (12 %), and ethanol (8 %). N-acetylcysteine was the most commonly administered antidote during 2011, similar to 2010, followed by the opioid antagonist naloxone, sodium bicarbonate, physostigmine and flumazenil. Anti-crotalid Fab fragments (CroFab) were administered in 106 out of 131 cases in which an envenomation occurred. There were 35 deaths recorded in the Registry during 2011. The most common associated agents, including when reported as sole agent or in combination with other agents, were opioids and analgesics (acetaminophen, aspirin, NSAIDS) with ten and eight deaths, respectively. Oxycodone was reported in six of the ten opioid-related deaths and heroin in three. Acetaminophen was the most common single agent reported overall being identified in all eight of the death cases attributed to analgesics. There were significant trends identified during 2011. Cases involving designer drugs including psychoactive bath salts and synthetic cannabinoids increased substantially from 2010 to 2011. The psychoactive bath salts were responsible for a large increase in stimulant/sympathomimetic-related cases reported to the Registry in 2011 with overall numbers doubling from 6 % of all Registry entries in 2010 to 12 % in 2011. Entries involving psychoactive drugs of abuse also increased twofold from 2010 to 2011 jumping 3 to 6 %, primarily due to increasing frequency of synthetic cannabinoid (“K2”) related intoxications as 2011 progressed. The 2011 Registry included over 600 ADR’s (10 % of Registry Cases) with 115 agents causing at least 2 ADR’s. This is up from only 3 % of cases (116 total cases) in 2010. The ToxIC Case Registry continues to grow. At the end of 2011, over 10,000 cases had been entered into the Registry. As demonstrated by the trends identified in psychoactive bath salt and synthetic cannabinoid reports, the Registry is a valuable toxicosurveillance and research tool. The ToxIC Registry is a unique tool for identifying and characterizing confirmed cases of significant or potential toxicity or complexity to require bedside consultation by a medical toxicologist.     

Use of hazard indices for a theoretical evaluation of cigarette smoke composition

The chemical composition of cigarette mainstream smoke (MS) has been quantitatively analyzed in multiple studies, often with the objective to toxicologically evaluate and compare various types of MS. Increases and decreases in yields of constituents between MS types can only be consolidated if these yields are compared on the basis of toxicological properties of the individual constituents. For the risk assessment of various complex mixtures including MS, a hazard index (HI) approach has been used that requires weighing of the exposure to individual MS constituents by cancer and noncancer potency values. The objective of the current study is to review the past uses of the HI concept for MS and smokeless tobacco and discuss strengths and limitations of using this concept. Published information as well as information made available on the Web was used. The HI concept has been applied to MS for determining and comparing theoretical lifetime risks, for consumer communication, for the prioritization of constituents for reduction, for ingredient assessment, and for the selection of constituents for regulation. The limitations of this approach are associated with the limited number of MS constituents with available yield data, the gaps and uncertainties in available potency values, the application to relatively high exposure concentrations, and the default assumption of additivity. The derived theoretical noncancer index is dominated by acrolein to an extent that there seems to be not much advantage in using the HI concept for noncancer assessments. The derived theoretical cancer index is dominated by genotoxic carcinogens of the MS vapor phase and may thus complement currently used toxicological assays in a tiered evaluation approach. As is the case for every other assay and interpretation model, the HI concept needs to be applied with its limitations and weaknesses in mind. Its best application is for comparative purposes. It should be kept in mind that the HI concept is a theoretical concept and does not provide actual risk information.