Sex-based differences in timely emergency department evaluations for patients with drug poisoning.

OBJECTIVES: Unintentional poisoning was the leading cause of injury-related death in the United States in 2017. Prescribed and illicit drugs are the most common cause of poisoning, and timely management in the emergency department (ED) is important. Our aim was to identify any disparities in wait times associated with sex for drug poisoning-related ED visits. STUDY DESIGN: We examined ED visits using data from the 2009-2017 National Hospital Ambulatory Medical Care Survey (NHAMCS). METHODS: Drug poisoning-related visits were identified using the International Classification of Diseases, Ninth or Tenth Revision, Clinical Modification codes. Delayed assessment was defined as wait times exceeding the recommended triage time. Weighted logistic regression was used. RESULTS: The average age was 36 years (standard error = 1.1), 54% female, 87% White and 29% had delayed assessment. Most common drugs were psychotropics (45%) and opioids (32%). Adjusting for race, payment source, urgency, multiple drug types and NSAIDs, females who had poisoning by substances other than opioids had 2.1 times higher likelihood of having a delayed assessment compared with males (odds ratio [95% confidence interval]: 2.1 [1.03-4.2]), although there was no difference between sexes among visits with opioid poisoning (P = 0.27). Neither race (P = 0.23) nor payment source (P = 0.22) were associated with delayed assessment, and the sex association was consistent across these groups. CONCLUSIONS: Females with non-opioid drug poisoning were more likely to have delayed assessment than men. None of the other demographic factors demonstrated a correlation. Identifying more populations vulnerable to delays in the ED can help guide the development of interventions and policies to expedite care and attenuate existing disparities.

Personalized medicine approaches in epilepsy.

Epilepsy affects 50 million persons worldwide, a third of whom continue to experience debilitating seizures despite optimum anti-epileptic drug (AED) treatment. Twelve-month remission from seizures is less likely in female patients, individuals aged 11-36 years and those with neurological insults and shorter time between first seizure and starting treatment. It has been found that the presence of multiple seizures prior to diagnosis is a risk factor for pharmacoresistance and is correlated with epilepsy type as well as intrinsic severity. The key role of neuroinflammation in the pathophysiology of resistant epilepsy is becoming clear. Our work in this area suggests that high-mobility group box 1 isoforms may be candidate biomarkers for treatment stratification and novel drug targets in epilepsy. Furthermore, transporter polymorphisms contributing to the intrinsic severity of epilepsy are providing robust neurobiological evidence on an emerging theory of drug resistance, which may also provide new insights into disease stratification. Some of the rare genetic epilepsies enable treatment stratification through testing for the causal mutation, for example SCN1A mutations in patients with Dravet's syndrome. Up to 50% of patients develop adverse reactions to AEDs which in turn affects tolerability and compliance. Immune-mediated hypersensitivity reactions to AED therapy, such as toxic epidermal necrolysis, are the most serious adverse reactions and have been associated with polymorphisms in the human leucocyte antigen (HLA) complex. Pharmacogenetic screening for HLA-B*15:02 in Asian populations can prevent carbamazepine-induced Stevens-Johnson syndrome. We have identified HLA-A*31:01 as a potential risk marker for all phenotypes of carbamazepine-induced hypersensitivity with applicability in European and other populations. In this review, we explore the currently available key stratification approaches to address the therapeutic challenges in epilepsy.

A continuum of sleep and shallow torpor in fasting doves.

Fasting doves entered shallow torpor during nocturnal sleep. Body temperature dropped lower each successive night by 1 degrees to 3 degrees in parallel with diminished rapid-eye-movement sleep until torpor was composed almost entirely of slow-wave sleep at a body temperature of 30 degrees to 32 degrees C. Shallow torpor in doves, as in mammals, thus appears to lie on a metabolic continuum with sleep.

Antigens associated with a human lung adenocarcinoma defined by monoclonal antibodies.

Monoclonal antibodies KS1/4, KS1/9, and KS1/17 were developed in this laboratory from a fusion of the murine myeloma cell line P3X63Ag8 with spleens of BALB/c mice previously primed with UCLA P3 cells derived from a human adenocarcinoma of the lung. Monoclonal antibodies KS1/4 and KS1/17 seemed to recognize similar glycoprotein antigens on the lung carcinoma cells by indirect immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. However, mapping of [3H]lysine- and [3H]arginine-labeled tryptic peptides of antigens in specific immunoprecipitates of lung carcinoma cells by high-pressure liquid chromatography revealed a one peptide difference. Antibody KS1/9 did not immunoprecipitate any identifiable protein from detergent extracts of the immunizing cell line by routine methods and appears to detect a glycolipid antigen. Immunocytochemical analysis of tissue sections showed this monoclonal antibody to be reactive with adenocarcinomas of the lung and not with the other histological types of lung carcinoma or normal tissue. Monoclonal antibodies KS1/4 and KS1/17, however, reacted with 3 major histological types of lung cancer and minimally with the proximal tubules of normal kidney and the epithelium of bronchioles.

Antigens associated with human squamous cell lung carcinoma defined by murine monoclonal antibodies.

A panel of 12 monoclonal antibodies that preferentially react with human squamous lung carcinoma cells has been produced. All are reactive with fresh frozen sections of squamous cell lung carcinoma tissues in immunoperoxidase assays and are unreactive with lymphoblastoid cells, red blood cells, and fibroblasts in enzyme-linked immunosorbent assay. At least eight of these antibodies interact with cell surface components. These reagents can be subdivided into four groups based upon their reactivities. Groups 1 to 3 are unreactive with normal liver, lung, kidney, colon, spleen, and pancreas in immunoperoxidase assays. Group 1 antibodies (PF1/A, PF1/B, PF1/C, PF1/D, and PF1/E) are all of IgG3 subclass and immunoprecipitate nonsulfated glycoprotein components with molecular weights of 80,000 and 180,000 and a nonglycosylated polypeptide with a molecular weight of 38,000. Group 1 antibodies are also reactive with some lung adenocarcinomas and, with the exception of PF1/E, stain certain differentiated strata within normal adult plantar and fetal epidermis. Group 2 antibodies (PF2/A and PF2/B) react also with breast, gastric, and colonic adenocarcinomas and some tumors of neuroectodermal origin. Group 2 antibodies, which are both of IgG3 subclass immunoprecipitate a nonglycosylated Mr 24,000 polypeptide. Group 3 antibodies (PF3/A, an IgG1; PF3/B, an IgGM; and PF3/C, an IgG2a) react additionally with certain other tumors, as well as with normal adult and fetal epidermis. Group 4 antibodies (PF4/A, an IgG2a; and PF4/B, an IgG1) are less specific than those of the preceding groups, as they react with some normal tissues, including pancreatic islets and pneumocytes, as well as with a variety of adenocarcinomas and tumors of neuroectodermal origin. PF4/A and PF4/B immunoprecipitate Mr 100,000 and 95,000 glycoproteins, respectively.

Biosynthesis and glycosylation of the carcinoma-associated antigen recognized by monoclonal antibody KS1/4.

Monoclonal antibody KS1/4 recognizes an epitope expressed on the cell surface of human adenocarcinoma cells and certain epithelia. Western blotting analyses of tumor cell extracts utilizing KS1/4 reveal staining of a major Mr 40,000 band and a minor Mr 42,000 band. Both components are also detectable in KS1/4 immunoprecipitates of L-[35S]methionine- and D-[3H]glucosamine-labeled human lung tumor cell extracts. When synthesis occurs in the presence of tunicamycin or when the immunoprecipitates are treated with peptide:N-glycosidase F, a single polypeptide component (Mr 37,000) is precipitated. Immediately following translation, digestion of Mr 40,000 and Mr 42,000 glycoproteins with endo-beta-N- acetylglucosaminidase H also yields a single polypeptide component at Mr 37,000. However, over a 3-h period beginning at 10 min posttranslation, a Mr 39,000 major component and a Mr 41,000 minor component gradually appear in the endo-beta-N-acetylglucosaminidase H digests as the Mr 37,000 component gradually disappears. Analysis of tryptic glycopeptides derived from the Mr 40,000 and 42,000 components suggests that the two components differ by the addition of one extra oligosaccharide to the Mr 42,000 component. Nonequilibrium pH gradient electrophoresis/sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of KS1/4 immunoprecipitates resolves each of the two components into multiple spots. Digestion of the KS1/4 immunoprecipitates with neuraminidase prior to two-dimensional analysis or immunoprecipitation of short pulse-labeled extracts reduces the number of spots to three each at the Mr 40,000 and Mr 42,000 positions. Digestion of the KS1/4 immunoprecipitates with peptide:N-glycosidase F, immunoprecipitation of extracts labeled in the presence of tunicamycin, or endo-beta-N-acetylglucosaminidase H digestion of immunoprecipitates of short pulse-labeled extracts prior to two-dimensional analysis results in a single series of Mr 37,000 spots, suggesting that the polypeptide portions of the Mr 40,000 and Mr 42,000 components may be identical. Endo-beta-N-acetylglucosaminidase H digestion of KS1/4 immunoprecipitates of short pulse-labeled extracts, followed by nonequilibrium pH gradient electrophoresis, V8 protease digestion, and polyacrylamide gel electrophoresis revealed an apparently identical set of polypeptides derived from each of the three Mr 37,000 spots, suggesting that the three spots derive from highly similar polypeptides.

Phase I clinical comparative study of monoclonal antibody KS1/4 and KS1/4-methotrexate immunconjugate in patients with non-small cell lung carcinoma.

A Phase Ia clinical trial was undertaken to evaluate and compare murine monoclonal antibody KS1/4 and KS1/4-methotrexate immunoconjugate in patients with Stage IIIB or IV non-small cell carcinoma of the lung. Six patients received KS1/4 alone and five patients received KS1/4-methotrexate conjugate. The maximal total dose received per patient in both groups was 1661 mg. Mild to moderate side effects in both groups included fever, chills, anorexia, nausea, vomiting, diarrhea, anemia, and brief transaminasemia. One patient who received antibody alone had an apparent acute immune complex-mediated reaction. Ten of 11 patients had a human anti-mouse response. Posttreatment carcinoma biopsies revealed binding of monoclonal antibody KS1/4 and deposition of C3d and C4c complement fragments. Monoclonal antibody binding and complement deposition correlated with increasing doses of infused antibody. There was one possible clinical response.

Structure--activity relationships of sialyl Lewis x-containing oligosaccharides. 1. Effect of modifications of the fucose moiety.

Leukocyte adhesion to the vasculature is mediated by E-, P-, and L-selectins. The natural ligands for E- and P-selectins have not been fully characterized but have been shown to contain the tetrasaccharide sialyl Lewis x structure (SLe(x)). To determine the importance of the fucose moiety of SLe(x), various analogs of SLe(x) containing modifications thereof were prepared and tested as inhibitors of E-selectin-mediated cell adhesion. Cellular experiments indicate that replacement of the hydroxyl groups of fucose by hydrogen abrogated E-selectin binding. However, the arabinose analog of fucose (CH3 delta H) inhibited cell adhesion but was 5-fold less potent than native SLe(x). This data suggests that modifications of fucose on SLe(x) are generally deleterious toward E-selectin binding.

Ear oximetry to detect apnea and differentiate rapid eye movement (REM) and non-REM (NREM) sleep. Screening for the sleep apnea syndrome.

Ear oximetry is commonly employed in screening patients for the sleep apnea syndrome, but the lack of objective information regarding the duration of sleep, including the presence of rapid-eye-movement (REM) sleep, is a major limitation. Based on the premise that both apnea and sleep-state-dependent changes in ventilation give rise to distinctive patterns in the arterial oxygen saturation, we developed a systematic technique to analyze ear oximetric tracings for wakefulness, REM sleep, and non-REM (NREM) sleep. Fifty-four patients were studied by both all-night polysomnography and ear oximetry. A careful comparison of ear oximetric data for sleep states and apnea was then made, using polysomnography as the correct classification to determine sensitivity, specificity, predictive value positive, and predictive value negative of the ear oximetric tracings. When classification of sleep state was compared, ear oximetry correctly classified 280.5 (82 percent) of 340.9 hours of sleep that was either REM or NREM sleep. The sensitivity for classifying NREM sleep was 0.85, for REM sleep was 0.70, and for wakefulness was 0.49. The sensitivity by ear oximetry for apnea was 0.80, with a predictive value negative of 0.87. We conclude that although polysomnography must be performed for definitive evaluation, ear oximetry is a valuable screening test for sleep apnea because the presence or absence of apnea can be determined, total duration of sleep can be estimated, and NREM vs REM sleep can be differentiated.

Within-session determination of dose-response curves for heroin self-administration in rats: Comparison with between-session determination and effects of naltrexone.

A procedure was employed in the present study to obtain dose-response curves for heroin self-administration within each experimental session. The data generated using this procedure were compared to dose-response data obtained using between-session dose manipulations. The dose of heroin (18, 30, 60 or 100 micrograms/kg/inf) was varied across 4-hourly segments separated by a 20-min time-out period during which heroin was not available. The within-session dose-response procedure yielded data similar to those obtained using between-session dose manipulations when the order of dose presentation was increasing or random. However, the dose-response curve for total drug-intake was flat when the doses were presented in decreasing order. Further analysis of the dose-response curves in the within-session procedure demonstrated that the rate of heroin intake increased in the third and fourth hourly components compared to the first component, suggesting acute tolerance to the reinforcing and/or rate-suppressive effects of heroin. Furthermore, using a random order of dose presentation, administration of 3.0 mg/kg of naltrexone prior to the session shifted the dose-response curve for heroin self-administration 5-fold to the right in the within-session procedure. The data indicate that the within-session dose-response procedure can be used to investigate the pharmacology of heroin self-administration in rodents.

Psychology and violence against women.

The discipline of psychology has made many contributions to the understanding of the social problem of men's violence against women during the past 15 years by reframing the problem as one of misuse of power by men who have been socialized into believing they are entitled to control the women in their lives, even by violent means. The new scientific psychology data base formed by integrating feminist gender analysis methods into more traditional psychological methodology is discussed, as are the implications of the resulting empirical data on which are based newer assessment, treatment, and forensic applications. A review of the major psychological advances in psychotherapy with women who have been sexual assaulted, exploited, and battered is presented, as well as implications for national policy. The feminist model presented is one in which science and practice concerns are carefully considered at all steps of the process. The article concludes with a discussion of the challenges involved in making the future training of psychologists more relevant to women's mental health concerns.

Dose-effect functions for cocaine self-administration: effects of schedule and dosing procedure.

Research related to determining how procedural variables can alter dose-effect functions for cocaine self-administration is limited. Toward clarifying the role of procedural variables, responding was maintained in rats under either variable-interval (VI) or fixed-ratio (FR) schedules of cocaine infusion. In addition to free-operant FR schedules, discrete-trial FR schedules were evaluated. The dose-effect functions were obtained by either substituting a dose for the usual daily dose, instituting a particular dose for several sessions, or making all doses available within a session. Dose-effect functions for response rate (or number of trials with infusions for the discrete-trial FR) were bitonic for the VI and discrete-trial FR schedules but tended to be strictly decreasing for the free-operant FR schedules. Responding was maintained under FR schedules by a low dose (0.083 mg/infusion) if the dose was substituted for a higher daily dose but not when made available daily. Rate of response was higher under ratio schedules at 0.17 mg/infusion when this dose occurred within the context of other higher doses within a session than when the dose was simply substituted for a higher daily dose. These data indicate that procedural variables can alter dose-response curves for cocaine self-administration.

Clinical relevance of positive breast periprosthetic cultures without overt infection.

The true incidence of positive breast periprosthetic cultures in the absence of overt infection is not clearly established. We retrospectively reviewed data from 389 implants that were removed for reasons other than clinical infection. Many of these patients presented with a variety of musculoskeletal ailments. Others had symptomatic capsular contracture as the presenting complaint. In a few a known implant rupture was the reason for explantation. We identified a positive culture rate of 23.5 percent from capsule tissue. Most of these organisms were coagulase-negative staphylococci and anaerobic diphtheroids, but fungi and other organisms (generally felt to be more pathogenic than the less virulent coagulase-negative staphylococci) also were cultured. In an attempt to identify the clinical relevance of these positive cultures, we statistically evaluated the culture results for associations with capsular contracture, implant rupture, type of implant, and location of implant. Of these, the only statistically significant correlation was between positive culture result and symptomatic capsular contracture (Baker class IV).

A review of 198 patients (389 implants) who had breast implants removed.

Because of the large number of women now returning to their plastic surgeons with concerns about their breast implants many years after surgery, we are afforded an ideal opportunity to evaluate these patients over the long-term. This study reviewed 198 patients (389 implants) who underwent explantation by two surgeons over a 2-year period, correlating prosthesis type, location, and length of time since implantation with two adverse endpoints, implant rupture and symptomatic capsular contracture. Significant findings included a relatively high rate of implant rupture in patients whose implants had been in place over 20 years, an increased incidence of both symptomatic capsular contracture and implant rupture in single lumen gel implants and a positive correlation between severity of capsular contracture and implant rupture.