Evaluation of N-acetylcysteine dose for the treatment of massive acetaminophen ingestion.

METHODS: The use of N-acetylcysteine (NAC) remains the standard of care for treatment of acetaminophen (APAP) toxicity and overdose. Currently, there is growing evidence to suggest that massive acetaminophen overdose is associated with increased hepatotoxicity despite timely administration of NAC. This raises the question as to whether an increased dose of intravenous (IV) NAC should be used in the setting of massive APAP ingestion. This study aimed to evaluate the rate of hepatotoxicity after massive APAP overdose treated with 3 different NAC treatment regimens. METHODS: This was a retrospective cohort study conducted by electronic medical record review of cases reported to a statewide poison control system between 2007 and 2020. Inclusion criteria were single APAP or APAP combination-medication ingestion; acute massive acetaminophen (APAP) ingestion (defined as APAP concentration ≥ 2 times above the Rumack-Matthew 150 nomogram); received one of the three NAC regimens: standard dose IV NAC, oral (PO) NAC, or high dose IV NAC. The risk of hepatotoxicity was evaluated using a multivariate logistic regression model with standard dose IV NAC as the base variable for comparison. RESULTS: A total of 373 patients met inclusion for the study. Of those, 135 cases were treated with standard dose IV NAC, 121 cases treated with PO NAC, and 117 cases treated with high dose IV NAC. The risk of developing hepatotoxicity was not statistically significant between the high dose IV NAC (OR 1.05, 95% CI 0.52 - 2.09) or oral NAC (OR 0.69, 95% CI 0.33 - 1.46) when compared to standard dose IV NAC. When adjusted for APAP combination medications, initial APAP ratio, initial elevated AST/ALT, and treatment within 8 h, there remained no difference between treatment regimens. CONCLUSION: This study was unable to detect a large absolute reduction in the rate of hepatotoxicity after massive APAP ingestion in patients treated with high dose IV NAC or PO NAC when compared to standard dose IV NAC; even when treatment was initiated within 8 h of ingestion.

Altered mental status and end organ damage associated with the use of gacyclidine: a case series.

INTRODUCTION: Over the past decade, there has been a sharp increase in the number of newly identified synthetic drugs. These new drugs are often derivatives of previously abused substances but have unpredictable toxicity. One of these drugs is gacyclidine, a derivative of phencyclidine (PCP). Gacyclidine has been studied as a neuroprotective agent in trauma and as a therapy of soman toxicity. There are no previous reports of its use as a drug of abuse. CASE REPORTS: During a two-month period in the summer of 2013, a series of patients with severe agitation and end-organ injury were identified in an urban academic Emergency Department (ED). A urine drug of abuse screen was performed on all patients, and serum samples were sent for comprehensive toxicology analysis. A total of five patients were identified as having agitation, rhabdomyolysis, and elevated troponin (Table 1). Three of the five patients reported use of methamphetamine, and all five patients had urine drug screens positive for amphetamine. Comprehensive serum analysis identified methamphetamine in three cases, cocaine metabolites in one case, and a potential untargeted match for gacyclidine in all five cases. No other drugs of abuse were identified. DISCUSSION: This is the first series of cases describing possible gacyclidine intoxication. The possible source of the gacyclidine is unknown but it may have been an adulterant in methamphetamine as all patients who were questioned reported methamphetamine use. These cases highlight the importance of screening for new drugs of abuse when patients present with atypical or severe symptoms. Gacyclidine has the potential to become a drug of abuse both by itself and in conjunction with other agents and toxicity from gacyclidine can be severe. It is the role of the medical toxicology field to identify new agents such as gacyclidine early and to attempt to educate the community on the dangers of these new drugs of abuse.

Alternative drugs of abuse.

The incidence of drug abuse with alternative agents is increasing. The term "alternative drugs of abuse" is a catch-all term for abused chemicals that do not fit into one of the classic categories of drugs of abuse. The most common age group abusing these agents range from 17 to 25 years old and are often associated with group settings. Due to their diverse pharmacological nature, legislative efforts to classify these chemicals as a schedule I drug have lagged behind the development of new alternative agents. The potential reason for abuse of these agents is their hallucinogenic, dissociative, stimulant, anti-muscarinic, or sedative properties. Some of these drugs are easily obtainable such as Datura stramonium (Jimson Weed) or Lophophora williamsii (Peyote) because they are natural plants indigenous to certain regions. The diverse pharmacology and clinical effects of these agents are so broad that they do not produce a universal constellation of signs and symptoms. Detailed physical exams are essential for identifying clues leading one to suspect an alternative drug of abuse. Testing for the presence of these agents is often limited, and even when available, the results do not return in a timely fashion. Intoxications from these agents pose unique challenges for health care providers. Physician knowledge of the physiological effects of these alternative agents and the local patterns of drug of abuse are important for the accurate diagnosis and optimal care of poisoned patients. This review summarizes the current knowledge of alternative drugs of abuse and highlights their clinical presentations.

Climate change and impacts in the Eastern Mediterranean and the Middle East.

The Eastern Mediterranean and the Middle East (EMME) are likely to be greatly affected by climate change, associated with increases in the frequency and intensity of droughts and hot weather conditions. Since the region is diverse and extreme climate conditions already common, the impacts will be disproportional. We have analyzed long-term meteorological datasets along with regional climate model projections for the 21st century, based on the intermediate IPCC SRES scenario A1B. This suggests a continual, gradual and relatively strong warming of about 3.5-7°C between the 1961-1990 reference period and the period 2070-2099. Daytime maximum temperatures appear to increase most rapidly in the northern part of the region, i.e. the Balkan Peninsula and Turkey. Hot summer conditions that rarely occurred in the reference period may become the norm by the middle and the end of the 21st century. Projected precipitation changes are quite variable. Annual precipitation is expected to decrease in the southern Europe - Turkey region and the Levant, whereas in the Arabian Gulf area it may increase. In the former region rainfall is actually expected to increase in winter, while decreasing in spring and summer, with a substantial increase of the number of days without rainfall. Anticipated regional impacts of climate change include heat stress, associated with poor air quality in the urban environment, and increasing scarcity of fresh water in the Levant.

Regulation of neuronal traits by a novel transcriptional complex.

The transcriptional repressor, REST, helps restrict neuronal traits to neurons by blocking their expression in nonneuronal cells. To examine the repercussions of REST expression in neurons, we generated a neuronal cell line that expresses REST conditionally. REST expression inhibited differentiation by nerve growth factor, suppressing both sodium current and neurite growth. A novel corepressor complex, CoREST/HDAC2, was shown to be required for REST repression. In the presence of REST, the CoREST/HDAC2 complex occupied the native Nav1.2 sodium channel gene in chromatin. In neuronal cells that lack REST and express sodium channels, the corepressor complex was not present on the gene. Collectively, these studies define a novel HDAC complex that is recruited by the C-terminal repressor domain of REST to actively repress genes essential to the neuronal phenotype.

Regulation of transcriptional activation domain function by ubiquitin.

The ability of transcriptional activation domains (TADs) to signal ubiquitin-mediated proteolysis suggests an involvement of the ubiquitin-proteasome pathway in transcription. To probe this involvement, we asked how ubiquitylation regulates the activity of a transcription factor containing the VP16 TAD. We show that the VP16 TAD signals ubiquitylation through the Met30 ubiquitin-ligase and that Met30 is also required for the VP16 TAD to activate transcription. The requirement for Met30 in transcription is circumvented by fusion of ubiquitin to the VP16 activator, demonstrating that activator ubiquitylation is essential for transcriptional activation. We propose that ubiquitylation regulates TAD function by serving as a dual signal for activation and activator destruction.

A multisite field test of the acceptability of physical activity counseling in primary care: project PACE.

Primary health-care providers have been encouraged to counsel their patients about regular physical activity, but there are significant barriers to effective counseling. In this study a program of training and materials was tested for acceptability to providers, office staff, and patients. Primary care providers and office staff were trained to use the Physician-based Assessment and Counseling for Exercise (PACE) materials in four geographical sites in the United States. The program was tested in a variety of settings and with diverse patient populations. The acceptability of the program during a five-month study period was evaluated through structured interviews. The training was effective in preparing the providers to counsel, and the program was generally acceptable to providers, office staff, and patients. Counseling was provided in less than five minutes by 70% of providers, and most patients reported following the recommendations given. The PACE program assists providers in overcoming barriers to counseling patients about physical activity. The PACE program is potentially an important part of a national effort to enhance the adoption and maintenance of physical activity among adults.

Fluid collections developing after pancreatic transplantation: radiologic evaluation and intervention.

The usefulness of real-time sonography, duplex sonography, computed tomography (CT), cystography, diagnostic aspiration, and percutaneous drainage in the diagnosis and treatment of peri-pancreatic-transplant fluid collections was retrospectively assessed in 46 recipients of extraperitoneal pancreatic transplants. Forty-four abnormalities were identified in the extraperitoneal space at sonography, including four pancreatic pseudocysts associated with malfunction of the pancreatic duct, seven abscesses, six hematomas, nine urinomas, six early postoperative fluid collections that spontaneously resolved, six cases of pancreatitis, and six cases of vascular occlusion. Sonography (including pulsed Doppler sonography) was the procedure of choice in detecting fluid collections and diagnosing pancreatitis, rejection, vascular thrombosis, and pancreatic duct malfunction. CT was diagnostic in four of six hematomas; cystography was diagnostic in seven of nine urinomas. Sonographically guided percutaneous intervention enabled three patients to avoid surgery and allowed optimal surgical planning for six patients.

Needle holder for use with a biopsy gun.

The authors designed and constructed a simple needle holder device for maintaining the position of the trocar and cannula before performance of computed tomography (CT)- and ultrasonography-guided biopsies with a biopsy gun. The holder can be removed before attachment of the biopsy gun and routine obtaining of tissue. Use of the holder facilitated quicker and easier CT-guided biopsies of the liver (n = 3), pancreas (n = 1), and adrenal gland (n = 1) and of a chest wall tumor.

Teleradiology image transmission system: diagnostic accuracy at three matrix sizes for various types of images.

The interpretability of transmitted digitized radiographic images is an important factor in the operation and use of teleradiology systems. Matrix size may influence diagnostic accuracy of the interpretation. Commercially available equipment has certain built-in image enhancement controls that may increase the interpretability of the image received. Evaluation of the effect of varying the matrix size and other factors on diagnostic accuracy are described.

Computed tomography demonstration of inferior lumbar (Petit's) hernia.

Inferior lumbar (Petit's) hernia is an uncommon condition resulting from a defect in the posterior abdominal wall. Such hernias may be difficult to diagnose on the basis of physical signs and symptoms. A case of unsuspected inferior lumbar hernia clearly demonstrated by computed tomography (CT) is presented. Computed tomography is useful in determining the size and contents of the hernia, permitting accurate diagnosis, and planning treatment.

X-File: a program for maintaining a radiographic teaching file.

Software designed for entry, retrieval, and maintenance of radiographic case-file data on a microcomputer offers considerable help in maintaining such records in a radiology department. The case files are based on the Index for Roentgen Diagnoses, published by the AmericanCollege of Radiology. The terms and code numbers of the index are included in the software, so that the user need only enter the diagnostic term desired; the code numbers and exact terminology are assigned automatically. The software is written for an IBM-compatible microcomputer. Residents and staff radiologists have been using the program for the past two years to store and find both confirmed cases and other interesting cases. The system's capacity exceeds 70,000 entries on a 20-megabyte had disk. The program has five features not found in previous similar programs and not attainable with manual methods.

Diagnostic accuracy of a teleradiology image transmission system.

Teleradiology is the remote interpretation of digitized radiographic images by physicians. The images are usually transmitted over telephone lines, but satellite communication has also been used. The interpretability of the transmitted image is an important factor in the operation and use of teleradiology systems. Commercially available equipment has certain built-in functions that may enhance the interpretability of the image received. These functions and their usefulness in diagnosis are described. It is also possible to enhance the image for transmission, prior to digitizing, by certain manual techniques. These may be of value in situations where the first transmission is lacking in some quality. A test of these functions and techniques is reported.

Computed tomographic evaluation of paraesophageal hernia.

Paraesophageal hernias are relatively rare compared to the more commonly diagnosed sliding hiatus hernia. They tend to be asymptomatic initially, but may gradually enlarge and present with life-threatening complications. The treatment is surgical reduction, preferably as an elective procedure. Computed tomography (CT) clearly demonstrates a paraesophageal hernia through a widened esophageal hiatus, often as an incidental finding, and accurately documents the size, contents, and orientation of the herniated stomach within the lower thoracic cavity. In this report, the CT appearance of 4 patients with paraesophageal hernias is described along with a discussion of this uncommon but important surgical condition.