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.     

Platelets modulate the proteolysis of factor VIII:C protein by plasmin

Factor VIII coagulant protein (VIII:C) functions as a critical cofactor with factor IXa, calcium ions, and phospholipid during the activation of factor X. In the course of this reaction, the activity of VIII:C is first increased and then is destroyed by one or more serine proteases that are part of the coagulation sequence. In this study, we have investigated the influence of platelets on the inactivation of VIII:C by plasmin. Platelets were separated from plasma proteins in the presence of granule release inhibitors and were incubated with plasmin and isolated VIII:C or the complex of purified VIII:C/von Willebrand factor (vWF); VIII:C activity and antigen levels were assessed over time. In the presence of platelets, the isolated VIII:C showed an initial increase in VIII:C activity that was not present when platelets were absent, and the VIII:C/vWF showed an increase in VIII:C activity over that seen when platelets were absent. In addition, platelets stabilized VIII:C activity over a one-hour time course when compared with buffer. The VIII:C antigen did not increase and decreased slowly whether platelets were present or absent. Preincubating the platelets with ristocetin, collagen, or plasmin did not alter the results, and experiments using platelets from a patient with severe von Willebrand's disease also showed a pattern similar to that seen with normal platelets. Experiments using fixed platelets or phospholipid vesicles showed that they did not support the activation reaction or delay the inactivation reaction. These studies demonstrate that platelets modulate the activation and inactivation of VIII:C by plasmin, apparently by a mechanism that is independent of the platelet release reaction.     

Poliomyelitis eradication: progress, challenges for the end game, and preparation for the post-eradication era

In 1988, the World Health Assembly resolved to eradicate poliomyelitis globally by the year 2000. Dramatic progress toward this goal has occurred: three of the six WHO regions (Region of the Americas, European Region, and Western Pacific Region) are now polio free; and the number of polio-endemic countries decreased from over 125 in 1988 to 30 in 1999. Intensified efforts currently are underway to reach the target as soon as possible after 2000 in the three remaining polio-endemic WHO regions (African Region, Eastern Mediterranean Region, and South-East Asia Region). Even in polio-endemic regions, many countries are already polio free as the geographic extent of poliovirus shrinks while others. especially those experiencing conflict and war, pose substantial challenges to implementing the proven polio eradication strategies. Increasing attention and research now are devoted to the certification of polio eradication in the polio-free regions (that will include the first phase of implementing the Global Plan of Action for the laboratory containment of wild poliovirus) and formulating a policy for stopping all polio vaccination once eradication, containment, and global certification have been achieved. This report outlines the progress toward polio eradication and highlights some of the remaining issues and challenges that must be addressed before polio becomes a disease that future generations know only by history.     

The Selvester 32-point QRS score for evaluation of myocardial infarct size after primary coronary angioplasty

In patients treated successfully with primary angioplasty for a first myocardial infarction, the Selvester 32-point score correlates well with infarct size measured with quantitative thallium-201 perfusion imaging. Therefore, it is a useful parameter for infarct sizing, particularly in patients with anterior infarction or reduced ejection fraction at discharge.     

Epidemic diphtheria in the Republic of Georgia, 1993-1996: risk factors for fatal outcome among hospitalized patients

Epidemic diphtheria reemerged in the republic of Georgia in November 1993. To identify risk factors for fatal outcomes, clinical and epidemiologic data on all hospitalized diphtheria patients were examined. Medical charts of patients from 1993-1995 were reviewed. A total of 659 cases and 68 deaths were identified (case fatality rate [CFR] = 10.3%). Fifty-two percent of all cases and 68% of deaths were in children 3 days) between onset of symptoms to antitoxin treatment were significantly associated with fatal outcomes. Immunization of children and 40- to 49-year-old adults was required to rapidly control the epidemic.     

Measles among the Amish: a comparative study of measles severity in primary and secondary cases in households

An outbreak of measles among a predominantly unvaccinated and susceptible Amish population in Lebanon County, Pennsylvania, offered the opportunity to test the hypothesis that secondary cases in households are more severe than primary cases because the former have more intense exposure and receive a greater virus inoculum. Of 130 measles cases reported between April and June 1988, 119 (92%) constituted a study of disease severity. Severity was assessed by determining frequency and duration of symptoms, length of any hospitalization, and number of days in bed. In a univariate analysis, fewer secondary cases had conjunctivitis (relative risk [RR], 0.67; 95% confidence interval [CI], 0.48-0.96) and headache (RR, 0.37; CI, 0.15-0.86), but more had earache (RR, 9.69; CI, 1.8-202.9) compared with primary cases. Secondary cases had a shorter mean duration of coryza (4.0 vs. 5.0 days, Student's t test, P = .08). However, a logistic regression model that matched by family and controlled for age and sex indicated that there were no significant differences in measles severity among primary and secondary cases in households.     

Intra- and intermodal integration of discrepant visual and proprioceptive action effects

Integration of discrepant visual and proprioceptive action effects puts high demands on the human information processing system. The present study aimed to examine the integration mechanisms for the motor (Exp. 1) and visual modality (Exp. 2). According to theories of common coding, we assumed that visual as well as proprioceptive information is represented within the same cognitive domain and is therefore likely to affect each other (multisensory cross talk). Thus, apart from the often-confirmed visual dominance in multisensory integration, we asked about intra- and intermodal recall of either proprioceptive or visual information and whether there were any differences between the motor and visual modality. In a replication paradigm, we perturbed the relation between hand movements and cursor movements. The task required the (intra- vs. intermodal) replication of an initially performed (seen) hand (cursor) movement in a subsequent motor (visual) replication phase. First, mechanisms of integration were found to be dependent on the output modality. Visual action effects interfered the motor modality, but proprioceptive action effects did not have any effects on the visual modality. Second, however, intermodal integration was more susceptible to interference, and this was found to be independent from the output modality. Third, for the motor modality, the locus of perturbation (perturbation of cursor amplitude or perturbation of hand amplitude) was irrelevant, but for the visual modality, perturbation of hand amplitudes reduced the cross talk. Tool use is one field of application of these kinds of results, since the optimized integration of conflicting action effects is a precondition for using tools successfully.     

Hematopoietic growth factor expression and ATRA sensitivity in acute promyelocytic blast cells

Acute promyelocytic leukemia (APL) is a homogeneous subgroup of acute myeloid leukemias (AMLs) characterized by the presence of the t(15,17) translocation and the resulting promyelocytic myeloid leukemia/retinoic acid receptor alpha (PML/RAR alpha) fusion proteins. To date APL is the only AML that is sufficiently sensitive to all-trans retinoic acid's (ATRA) differentiating effect. In vivo ATRA alone achieves complete remission in most APL patients. However, failure or partial responses are observed and the molecular basis of the absence of ATRA response in these patients has not been determined. To gain insights in the cell growth and differentiation of APL cells, expression of hematopoietic growth factors (HGF) shown to be produced by leukemic cells (interleukin-1 beta [IL-1 beta], IL-6, tumor necrosis factor alpha (TNF alpha), granulocyte colony-stimulating factor [G-CSF], granulocyte- macrophage colony-stimulating factor [GM-CSF], and IL-3) was studied in 16 APL samples. Twelve APL cases expressed IL-1 beta, IL-6, and TNF alpha, but not G-CSF, GM-CSF, and IL-3. These cases achieved complete remission with ATRA therapy. The four remaining patients (either TNF alpha negative or G-CSF, GM-CSF or IL-3 positive) did not achieve complete remission with ATRA. In all cases, in vivo response to ATRA therapy was correlated to the in vitro differentiation effect of all- trans retinoic acid 10(-6) mol/L. Thus, ATRA differentiation induction was strongly correlated to the HGF expression (P < .0001). These results suggest that the presence or absence of HGF's expression by APL cells may contribute to the therapeutic effect of ATRA in this disease.     

Serum selenium and colonic neoplastic risk

BACKGROUND: Selenium deficiency has been associated with cancer risk in several organs. This association was investigated in neoplasia of the colorectum. DESIGN: A case-control study is reported with two patient series, colorectal cancer and colorectal adenomatous polyps, and a control group found to be free of colorectal neoplasia. Diagnosis was determined by colonoscopy and histologic review of suspected neoplasms. Serum drawn at the time of colonoscopy was subsequently assayed for selenium content, and quartiles based on selenium were defined. Crude and adjusted odds ratios with 95 percent confidence intervals for adenoma related to selenium were calculated, controlling for known or suspected risk factors including gender, age, race, body mass index, family history, tobacco use, alcohol consumption, serum beta carotene, serum alpha tocopherol, and serum ferritin. RESULTS: There were 138 controls who had no neoplastic disease, 139 adenoma patients, and 25 cancer patients. For adenoma,comparing higher quartiles of selenium to the first (lowest selenium), the adjusted odds ratio for the second quartile was 1.7 (95 percent confidence interval, 0.8–3.7), the third quartile was 1.4 (0.7–3.2), and the fourth (highest selenium) quartile was 1.8 (0.9–4). The odds ratios for cancer patients were 0.8 for the second quartile, 1 for the third quartile, and 1.7 for the fourth quartile. CONCLUSION: No trend could be detected toward a protective effect of higher levels of serum selenium for colonic benign or malignant tumors.Supported by grants from The American Society of Colon and Rectal Surgeons Research Foundation, the Department of Clinical Investigation of Walter Reed Army Medical Center, and Public Health Service Grant CA 36978.Address reprint requests to Dr. Nelson: 1740 West Taylor, Room 2204, M/C 957, Chicago, Illinois 60612.