Microbiological,biological, and chemical weapons of warfare and terrorism

Microbiological, biological, and chemical toxins have been employed in warfare and in terrorist attacks. In this era, it is imperative that health care providers are familiar with illnesses caused by these agents. Botulinum toxin produces a descending flaccid paralysis. Staphylococcal enterotoxin B produces a syndrome of fever, nausea, and diarrhea and may produce a pulmonary syndrome if aerosolized. Clostridium perfringens epsilon-toxin could possibly be aerosolized to produce acute pulmonary edema. Ricin intoxication can manifest as gastrointestinal hemorrhage after ingestion, severe muscle necrosis after intramuscular injection, and acute pulmonary disease after inhalation. Nerve agents inhibit acetylcholinesterase and thus produce symptoms of increased cholinergic activity. Ammonia, chlorine, vinyl chloride, phosgene, sulfur dioxide, and nitrogen dioxide, tear gas, and zinc chloride primarily injure the upper respiratory tract and the lungs. Sulfur mustard (and nitrogen mustard) are vesicant and alkylating agents. Cyanide poisoning ranges from sudden-onset headache and drowsiness to severe hypoxemia, cardiovascular collapse, and death. Health care providers should be familiar with the medical consequences of toxin exposure, and understand the pathophysiology and management of resulting illness.     

Unconventional biological threats and the molecular biological response to biological threats

This article concludes this symposium on potential agents of warfare and terrorism with discussion of 3 topics. First, influenza A virus is discussed as a potential biological weapon. Although it does not receive much attention in this role, the potential for mass casualties and public panic certainly exist if an epidemic of a virulent influenza A virus were initiated. Second, agroterrorism, terrorism directed at livestock or poultry or crops, is briefly discussed. Finally, the potential role of techniques of modern molecular biology to create new agents for bioterrorism or enhance the terrorist potential of available agents, and the known roles of these techniques in defense against biological warfare or terrorism are discussed.     

Enhanced detection of ischemic myocardium by transesophageal dobutamine stress echocardiography: comparison with simultaneous transthoracic echocardiography

The diagnostic accuracy of dobutamine stress echocardiography is limited in patients with poor transthoracic acoustic windows. Transesophageal echocardiography (TEE) overcomes these limitations and thus may increase the clinical usefulness of dobutamine stress echocardiography. The present study was designed to compare the diagnostic accuracies of transesophageal and transthoracic dobutamine stress echocardiography for the identification of coronary artery disease (CAD) in a cohort of patients with a higher incidence of poor acoustic windows. Forty-two male patients (mean age, 66 +/- 9 years) underwent dobutamine stress echocardiography with simultaneous transesophageal and transthoracic imaging. Coronary arteriography was performed in 28 patients (67%). Transesophageal imaging adequately visualized 99.6% of left ventricular segments compared with 76.2% visualized by transthoracic imaging (P < 0.0001). There was substantial agreement between the two techniques for segmental wall motion analysis at baseline (kappa 0.76; 95% CI, 0.70-0.82); however, at peak dobutamine dose, agreement was significantly reduced (kappa 0.62; 95% CI, 0.55-0.69). The sensitivity (88% vs 75%), specificity (100% vs 75%), and positive predictive value (100% vs 80%) for the identification of CAD were all superior for transesophageal imaging. Transesophageal imaging correctly identified 11 of the 12 patients (92%) with multivessel disease compared with 5 patients (42%) identified by transthoracic imaging (P < 0.03). There were no major complications. Transesophageal dobutamine stress echocardiography is a safe, feasible, and accurate technique for the identification and risk stratification of patients with CAD. Transesophageal imaging appears to be superior to transthoracic imaging for identifying both the presence and extent of CAD, specifically in patients with poor acoustic windows.     

Treatment of supraventricular tachycardias with transcatheter delivery of radiofrequency current.

Medical therapy for the treatment of supraventricular tachycardias is frequently ineffective and associated with significant side effects, whereas curative surgical approaches have generally been limited by their considerable morbidity and cost. Greater understanding of the mechanisms underlying supraventricular tachycardias has improved our ability to precisely map endocardial areas critical to arrhythmogenesis. Advances in catheter ablation techniques and particularly the use of radiofrequency current to generate thermal energy for ablation have resulted in dramatic success rates for curative catheter ablation. This review examines the physics of radiofrequency current ablation and its application to the treatment of atrial fibrillation, atrial flutter, AV nodal reentrant tachycardia, and arrhythmias associated with the Wolff-Parkinson-White syndrome. The limitations, risks, and cost-effectiveness of this technique relative to medical and surgical approaches are also evaluated.     

Functional and reactive hyperemia are unaltered by homocysteine in conscious dogs

Summary The purpose of this study was to test the hypothesis that L-homocysteine thiolactone (L-HCTL), through its reaction with adenosine to formS-adenosylhomocysteine, may modulate myocardial functional and reactive hyperemic responses. Reactive hyperemic responses to 10-sec occlusions or 400-msec diastolic occlusions of the circumflex coronary artery and functional hyperemic responses to ventricular extra-activations were studied in a chronic heart-blocked dog preparation during a control period and following L-HCTL (40 mg/kg). In two additional dogs multiple venous blood samples and left ventricular myocardial biopsies were obtained following L-HCTL to measure changes in plasma homocysteine and tissueS-adenosylhomocysteine. Despite a 75-fold increase in peak plasma homocysteine and a 26-fold increase in tissueS-adenosylhomocysteine, L-HCTL did not alter myocardial functional and reactive hyperemic responses.The rapid increase in myocardialS-adenosylhomocysteine confirmed cellular entry of homocysteine and its reaction with endogenous adenosine. The failure of L-HCTL to alter functional and reactive hyperemic responses suggests that either such treatment does not affect myocardial release of adenosine or that adenosine is not an important regulator of coronary flow.Supported in part by the National Institutes of Health Grants HL 18468 and AM 12828 and the Medical Research Service of the Veterans Administration. Dr. Sadick is a recipient of an Overseas Research Fellowship from the Australian National Heart Foundation. Parts of this work were presented at the 56th Scientific Sessions, American Heart Association, Anaheim, California, November, 1983.     

Stimulation by mammalian insulin of glycogen metabolism in a wall-less strain of Neurospora crassa

Addition of bovine insulin to cells of the wall-less variant FGSC4761 of Neurospora crassa ("slime") produced several significant effects on glycogen metabolism. 1) Intracellular levels of the glycogen precursor UDP-glucose decreased 17-18% (P less than 0.01) within 30 min of insulin addition. 2) Cells grown with insulin possessed 40% more glycogen than did control cells. 3) The incorporation of 14C-labeled glucose into glycogen increased 41% after 30-min treatment with 100 nM bovine insulin (P less than 0.01). 4) Insulin treatment of the cells caused activation of the enzyme glycogen synthase from a glucose-6-phosphate-dependent form to an independent form. Half-maximum activation occurred with 2 nM insulin. These are similar to insulin-induced effects in some mammalian cells. In contrast, no insulin-induced effect on glucose transport could be demonstrated in these cells.     

Age-dependent neurological phenotypes in a mouse model of PRRT2-related diseases

Paroxysmal kinesigenic dyskinesia is an episodic movement disorder caused by dominant mutations in the proline-rich transmembrane protein PRRT2, with onset in childhood and typically with improvement or resolution by middle age. Mutations in the same gene may also cause benign infantile seizures, which begin in the first year of life and typically remit by the age of 2 years. Many details of PRRT2 function at the synapse, and the effects of mutations on neuronal excitability in the pathophysiology of epilepsy and dyskinesia, have emerged through the work of several groups over the last decade. However, the age dependence of the phenotypes has not been explored in detail in transgenic models. Here, we report our findings in heterozygous and homozygous Prrt2 knockout mice that recapitulate the age dependence of dyskinesia seen in the human disease. We show that Prrt2 deletion reduces the levels of synaptic proteins in a dose-dependent manner that is most pronounced at postnatal day 5 (P5), attenuates at P60, and disappears by P180. In a test for foot slippage while crossing a balance beam, transient loss of coordination was most pronounced at P60 and less prominent at age extremes. Slower traverse time was noted in homozygous knockout mice only, consistent with the ataxia seen in rare individuals with biallelic loss of function mutations in Prrt2. We thus identify three age-dependent phenotypic windows in the mouse model, which recapitulate the pattern seen in humans with PRRT2-related diseases.

     

Alcohol content variation of bar and restaurant drinks in Northern California

Objective:  To estimate the average of and sources of variation in the alcohol content of drinks served on premise in 10 Northern Californian counties.
Methods:  Focus groups of bartenders were conducted to evaluate potential sources of drink alcohol content variation. In the main study, 80 establishments were visited by a team of research personnel who purchased and measured the volume of particular beer, wine, and spirit drinks. Brand or analysis of a sample of the drink was used to determine the alcohol concentration by volume.
Results:  The average wine drink was found to contain 43% more alcohol than a standard drink, with no difference between red and white wine. The average draught beer was 22% greater than the standard. Spirit drinks differed by type with the average shot being equal to one standard drink while mixed drinks were 42% greater. Variation in alcohol content was particularly wide for wine and mixed spirit drinks. No significant differences in mean drink alcohol content were observed by county for beer or spirits but one county was lower than two others for wine.
Conclusions:  On premise drinks typically contained more alcohol than the standard drink with the exception of shots and bottled beers. Wine and mixed spirit drinks were the largest with nearly 1.5 times the alcohol of a standard drink on average. Consumers should be made aware of these substantial differences and key sources of variation in drink alcohol content, and research studies should utilize this information in the interpretation of reported numbers of drinks.     

B-cell lymphoma after angioimmunoblastic lymphadenopathy: a case with oligoclonal gene rearrangements associated with Epstein-Barr virus

We describe a patient with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), who subsequently developed large-cell immunoblastic lymphoma of B-cell immunophenotype. At the time of the initial diagnosis, histologic examination of an inguinal lymph node showed typical features of AILD, and there was no evidence of a monoclonal B-cell population by immunohistochemical analysis. In situ hybridization and Southern blot analysis for Epstein-Barr virus (EBV) were negative. At autopsy 2 years later, the patient had widespread lymph node and organ involvement by large-cell immunoblastic lymphoma of B-cell immunophenotype. Southern blot analysis performed on DNA extracted from lymph nodes, liver, and spleen showed two patterns of Ig heavy chain and kappa light chain gene rearrangements. The T-cell receptor beta chain gene was in the germline configuration. Analysis with an EBV terminal repeat region probe showed two clonal populations that paralleled the Ig gene rearrangement studies. Double-labeling immunohistochemistry and in situ hybridization confirmed the presence of EBV within the neoplastic B cells. The data support the hypothesis that EBV was not etiologically related to AILD in this case, and that EBV proliferation may occur after the onset of the disease. Further, the data suggest that some B-cell lymphomas that arise in the setting of AILD resemble EBV-associated B-cell lymphomas that arise in other immunodeficiency states.