Differential modulation of glutamatergic transmission by 3,5-dibromo-L-phenylalanine

An increasing body of evidence supports the hypothesis that diminished function of N-methyl-D-aspartate (NMDA) receptors and the associated increase in glutamate release and overstimulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors are critical elements of the pathophysiology of schizophrenia. Here, we describe a halogenated derivative of the aromatic amino acid L-phenylalanine that 1) activates NMDA receptors, 2) depresses presynaptic glutamate release, and 3) blocks AMPA/kainate receptors. The experiments were conducted in rat cerebrocortical cultured neurons by using the patch-clamp technique. 3,5-Dibromo-L-phenylalanine (3,5-DBr-L-Phe) augmented NMDA miniature excitatory postsynaptic currents (mEPSCs) and activated the steady-state current, effects that were eliminated by NMDA receptor antagonists DL-2-amino-5-phosphonopentanoic acid and MK-801 (dizocilpine maleate; 5H-dibenzo[a,d]cyclohepten-5,10-imine). 3,5-DBr-L-Phe was a partial agonist at the glutamate-binding site of NMDA receptors with an EC50 of 331.6 +/- 78.6 microM and with an efficacy of 30.5 +/- 4.7% compared with NMDA. 3,5-DBr-L-Phe depressed both amplitude and frequency of AMPA/kainate mEPSCs. The IC50 of 3,5-DBr-L-Phe to inhibit AMPA/kainate mEPSC frequency was 29.4 +/- 4.3 microM. 3,5-DBr-L-Phe significantly decreased paired pulse depression of AMPA/kainate EPSCs and attenuated current activated by AMPA with higher efficacy at lower concentration of AMPA. 3,5-DBr-L-Phe neither affected GABA miniature inhibitory postsynaptic currents nor elicited action potentials. By enhancing NMDA receptor function, reducing glutamate release and blocking AMPA/kainate receptors 3,5-DBr-L-Phe represents a new type of polyvalent modulator of glutamatergic synaptic transmission with potential therapeutic applications.     

Reducing the incidence of surgical fires: supplying nasal cannulae with sub-100% O2 gas mixtures from anesthesia machines

In June 2003, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) recommended: "As a general policy, use air or FiO2 at < or =30% for open delivery (consistent with patient needs)" to prevent surgical fires. One way to interpret JCAHO's recommendation is that 100% O2 should not be indiscriminately used, and anesthesia providers should have the ability, consistent with patient needs and their clinical judgment, to deliver sub-100% O2 with nasal cannulae. An auxiliary O2 flowmeter has a barbed outlet connector that offers a convenient means to connect a cannula to an anesthesia machine and is routinely used for open delivery of 100% O2. The auxiliary O2 flowmeter provides only 100% O2 and thus does not allow titration of the O2 concentration to patient needs and may increase the risk of surgical fires. This report clarifies the JCAHO recommendation and describes different means of addressing it that are based primarily on using the anesthesia machine to blend a sub-100% O2 gas mixture and delivering it via a nasal cannula. The options presented depend on the model and manufacturer of the anesthesia machine and allow delivery via nasal cannula of O2 concentrations that range from 21% to 100%.     

Drug abuse by anesthesia personnel

Anesthesia personnel of 15 southeastern academic departments reported significantly less use of marijuana and cocaine among their staffs than did a class of medical students describing their own use. The chairmen reported that between 1% and 2% of anesthesia personnel came to their attention because of drug or alcohol abuse. Of 44 persons known to abuse drugs or alcohol, seven were reported to have died secondary to abuse.     

Immunogenicity and safety of inactivated influenza virus vaccine in young children in 2003-2004

This study assessed the safety and immunogenicity of a pediatric formulation of the 2003-2004 inactivated, trivalent, split virion influenza vaccine, administered in a 2-dose schedule in healthy children ages 6-36 months, of whom 94% had protective titers (> or =1/40) to at least 1 antigen. The 2003-2004 split virion influenza vaccine was safe and immunogenic in young children.     

Publisher's Note

Publishers Note

Publisher's Note     

Granzyme B: a marker of risk for influenza in institutionalized older adults

Risk for influenza increases with age while cellular immune responses decline. This was a prospective study to determine the relationship between cytokine and granzyme B levels in peripheral blood mononuclear cells stimulated with live influenza virus, and subsequent influenza illness. Granzyme B levels were lower in the group who later developed symptomatic laboratory-confirmed influenza (n=10) compared to the group who did not (n=90) (ANOVA, P=0.024). In contrast, none of the cytokine levels were related to the development of influenza. Thus, granzyme B is a potential marker of influenza risk in older adults.     

Emergence and possible transmission of amantadine-resistant viruses during nursing home outbreaks of influenza A (H3N2)

Outbreaks of influenza A (H3N2, A/Shanghai/11/87-like) occurred in two partially (60% and 79%) vaccinated nursing home populations in January 1988. A retrospective cohort study using chart review was designed to assess the effectiveness of influenza vaccination and amantadine prophylaxis (100 mg per day) in controlling the outbreaks and to determine the amantadine susceptibility of influenza viruses isolated from case-patients. The point estimate of vaccine efficacy in preventing influenza-like illness was -33% (95% confidence interval -115% to 18%). However, 9% of vaccinated case-patients died within 14 days after onset of influenza-like illness compared with 26% of unvaccinated case-patients (relative risk = 0.4, 95% confidence interval 0.1-1.0). There was no significant difference in illness severity among case-patients who became ill before amantadine prophylaxis was started (n = 84) compared with those who became ill while taking amantadine (n = 34). Four virus isolates obtained before amantadine prophylaxis was started demonstrated 52-68% inhibition by 1 microgram/ml of amantadine; by comparison, six isolates (resistant viruses) obtained from residents who became ill while taking amantadine demonstrated 1-18% inhibition. The resistant viruses had four different RNA sequences in the gene coding for the M2 protein transmembrane region. Three resistant viruses with identical RNA sequences were isolated from residents living in contiguous rooms who had onset of signs and symptoms during a 6-day interval. Further studies are needed to determine how frequently and under what circumstances resistant viruses occur when antiviral agents are used to control institutional influenza A outbreaks. Strategies for antiviral agent administration that limit the emergence and transmission of resistant virus strains may be needed.     

Growth of Staphylococcus aureus in Diprivan and Intralipid: implications on the pathogenesis of infections.

BACKGROUND: The incidence and severity of infections are increased when Intralipid or Diprivan are administered to patients. Intralipid promotes infection, presumably by inhibiting the reticuloendothelial system, thereby suppressing the host's constitutive immunity, whereas Diprivan supposedly promotes infection by supporting bacterial growth and increasing the inoculating dose. This study considers whether bacterial replication alone in Intralipid and Diprivan adequately explains the increased risk of infection associated with these agents or whether other factors might also be involved. METHODS: Staphylococcus aureus was cultured in 10% Intralipid or Diprivan at clinically relevant conditions or in Intralipid containing 0.005% (w/v) sodium EDTA, a current additive, to measure growth. To determine whether Intralipid affected infection, New Zealand white rabbits were injected intravenously with S. aureus with or without Intralipid. Twenty-four hours later, bacteria in lung, liver, spleen, and kidney tissues were enumerated. RESULTS: S. aureus failed to grow in Diprivan or Intralipid containing 0.005% EDTA. Whereas S. aureus did replicate in plain Intralipid, growth was delayed until the bacteria conditioned the media. Once initiated, growth was slow at clinically relevant temperatures. The administration of Intralipid to rabbits significantly increased the recovery of staphylococci from the kidneys, P < 0.001, relative to the other tissues 24 h after an intravenous inoculation with S. aureus, compared with rabbits receiving S. aureus with no Intralipid. CONCLUSIONS: These results suggest that Diprivan, and possibly Intralipid, represent poor media for the growth of S. aureus and may promote infection through mechanisms other than increased inoculum size.     

Mortality following isolation of various respiratory viruses in nursing home residents.

OBJECTIVE: To compare mortality following isolation of influenza A to mortality following isolation of other respiratory viruses in a nursing home. SETTING: The Wisconsin Veterans Home, a 688-bed skilled nursing facility for veterans and their spouses. PARTICIPANTS: All residents with respiratory viral isolates obtained between 1988 and 1999. DESIGN: Thirty-day mortality was determined following each culture-proven illness. RESULTS: Thirty-day mortality following isolation of viral respiratory pathogens was 4.7% (15/322) for influenza A; 5.4% (7/129) for influenza B; 6.1% (3/49) for parainfluenza type 1; 0% (0/26) for parainfluenza types 2, 3, and 4; 0% (0/26) for respiratory syncytial virus (RSV); and 1.6% (1/61) for rhinovirus. CONCLUSIONS: Mortality following isolation of certain other respiratory viruses may be comparable to that following influenza A (although influenza A mortality might be higher without vaccination and antiviral agents). The use of uniform secretion precautions for all viral respiratory illness deserves consideration in nursing homes.     

Computer-assisted capnogram analysis

Characteristic abnormal carbon dioxide waveforms from patients with mechanically ventilated lungs are observed when, for example, valves are incompetent, the airway is obstructed, the breathing circuit becomes disconnected, or a patient overrides mechanical ventilation with spontaneous breaths. Automated observation of the carbon dioxide waveform provides a uniform, concise, and consistent interpretation of the capnogram. This article describes a computer algorithm for analyzing and classifying capnograms as normal or as belonging to one of the categories above. The algorithm also generates a diagnostic message when the capnogram deviates from a learned norm for at least three consecutive waveforms (and thus reduces the influence of artifacts). Clinical experience shows reliable waveform recognition by the algorithm.Supported in part by a grant from Datascope Corporation.The authors thank David A. Paulus, MD, and Jeffrey M. Feldman, MD, for their assistance and advice.