Evaluation of the physician's ability to recognize the presence or absence of anemia, fever, and jaundice.

OBJECTIVE: The evaluation of the patient through a comprehensive history and physical examination is considered the cornerstone of medical diagnosis, but many studies suggest that physicians have inadequate physical examination skills. It is unknown whether these skills are reliable and whether they can be adequately acquired through training. The objective of this study was to evaluate the ability of the clinician to detect the presence and discriminate the extent of clinical anemia, fever, and jaundice in an ED or hospitalized patient. METHODS: This was a prospective observational study of a convenience sample of patients presenting to the ED or admitted to the hospital who had a rectal temperature measurement within 30 minutes prior to the observation, serum hematocrit measurement on the day of observation, or serum bilirubin measurement one day prior to the day of observation. Observers' (emergency medicine attending physicians', resident physicians', and rotating medical students') estimated serum hematocrit, rectal temperature, and serum bilirubin values were obtained after each observation. Sensitivity, specificity, positive predictive value, negative predictive value, and mean absolute difference between actual and estimated values were calculated for each observer. RESULTS: The physicians detected the presence or absence of anemia, fever, and jaundice in patients with sensitivities and specificities of approximately 70%. Their predictions varied from the measured value on average by 6.0 +/- 4.6% for serum hematocrit, 1.3 + 1.1 degrees F for rectal temperature, and 3.4 +/- 5.3 mg/dL for serum bilirubin. Observer accuracy decreased when evaluating patients with high and low measured values. CONCLUSIONS: The ability to correctly perform and interpret the physical examination appears to be independent of the observer level of training, patient ethnicity, or patient gender. The examination for pallor, warmth, and jaundice is unreliable in predicting the corresponding laboratory or electronic measurement. Certain anemic, febrile, or jaundiced patients may not be reliably detected solely by a focused physical examination.

Biphasic action of dextrorphan on penicillin induced bursting in rat hippocampal slice.

Effects of dextrorphan (DX), a metabolite of the over-the-counter antitussive, dextromethorphan, were investigated in rat hippocampal slices exposed to the epileptogenic agent penicillin. At 50 microM and 100 microM concentrations dextrorphan suppressed late components of the epileptiform CA1 field potential elicited by afferent electrical stimulation, and partially suppressed the intracellularly recorded paroxysmal depolarization shift. These effects were not due to non-specific changes in cell excitability, since resting cell membrane potential, input resistance, and the ability of cells to fire action potentials in response to direct depolarizing current were unaffected. The depressant effect of 100 microM dextrorphan was probably due to actions at the NMDA receptor, since pretreatment with the competitive NMDA antagonist D-APV prevented any further depressant effects of dextrorphan in this model. In contrast, at a 10 microM concentration DX enhanced the amplitude of evoked epileptiform field potentials and intracellularly recorded EPSPs. These findings support a role for dextrorphan and similar agents as anticonvulsants at high concentrations, but raise a caution regarding possible excitatory actions of dextrorphan at low concentrations.

Selective depression of N-methyl-D-aspartate-mediated responses by dextrorphan in the hippocampal slice in rat.

The effects of dextrorphan (DX) and dextromethorphan (DM) on responses to excitatory amino acids in the CA1 region of the hippocampus of the rat were studied using extracellular and intracellular recording in in vitro slices of brain. Dextrorphan selectively and non-competitively blocked depolarizations evoked by focally-applied N-methyl-D,L-aspartate (NMA), recorded by both extracellular and intracellular techniques. Quisqualate (QUIS) responses and evoked field potentials were not affected by DX. Epileptiform activity elicited in Mg2+-free solution was suppressed by DX. Dextrorphan had no effect on resting membrane potential or input resistance. The antagonism of NMA by DX was dose-dependent with an EC50 of 0.65 microM; DM was also effective but considerably less potent. In the paradigm used in the present study, DX did not produce the clear use-dependent block observed in the presence of MK-801. These data suggest that DX, the metabolite of the widely used antitussive DM, is a potent NMDA antagonist with a potential role as an anticonvulsant and neuroprotective agent.

Fade of the response to prolonged glutamate application in the rat hippocampal slice.

The effect of prolonged glutamate (GLU) application was examined on 60 CA1 pyramidal neurons in the in vitro rat hippocampal slice preparation. Continuous application of L-GLU, either by bath perfusion (0.5-2 mM) of the slices or iontophoresis (200 mM) into the dendritic region of the neurons, elicited a transient depolarization which faded to a mean of 53% of the initial peak amplitude despite continued exposure to the agonist. Membrane depolarization to aspartate (ASP) and the d-isomer of GLU also faded with time. In contrast, the depolarizing response to the excitatory amino acid agonists N-methyl-D,L-aspartate (NMA), quisqualate (QUIS), and kainate (KA) did not fade significantly during continuous application. The fade of the GLU depolarization was not affected by the NMDA antagonist D-2-amino-5-phosphonovalerate (APV) or by blocking synaptic transmission with tetrodotoxin. At the time of maximum fade of the GLU depolarization, there was no change in input resistance or GLU reversal potential. In addition, fade of the response was not a consequence of changes in extracellular potassium concentration, GLU uptake mechanisms, or the electrogenic pump. The most likely explanation for fade is postsynaptic receptor desensitization.

The influence of skeletal muscle on the electrical excitability of dorsal root ganglion neurons in culture.

Dorsal root ganglion (DRG) neurons from embryonic mice grown in coculture with dissociated skeletal muscle or in skeletal muscle conditioned medium (CM) showed an increased incidence of repetitive firing of action potentials when injected with sustained (60-100 msec) depolarizing current. This is in contrast to DRG neurons grown in monoculture and normal medium, which exhibit such behavior far less frequently. The first action potential showed less sensitivity to block with TTX and more sensitivity to Ca2+ channel blockers than the subsequent action potentials. The increased incidence of repetitive firing occurred when CM was added after as few as 2 or as many as 22 d in culture and with as little as 1-7 hr exposure to CM. This effect of CM cannot be mimicked by NGF or by coculture with cells from embryonic spinal cord (Peacock et al., 1973), can be eliminated by heating the CM at 56 degrees C for 30 min, and partially reversed following short exposure to CM. These results indicate that skeletal muscle releases some heat-labile factor(s) that can cause repetitive firing and, in addition, significant decrease in input resistance in the CM-treated neurons and a depression of the anomalous rectification, neither of which could account for the increase in repetitive firing.

The pharmacology of cholinergic excitatory responses in hippocampal pyramidal cells.

The pharmacology of excitatory cholinergic responses in CA1 pyramidal cells was examined in detail using intracellular recording from the hippocampal slice preparation. Acetylcholine (ACh), carbachol, muscarine and pilocarpine depolarized the membrane potential with an associated increase in input resistance. In addition, these agonists increased cell firing and depressed the afterhyperpolarization (AHP) that is due to a calcium-activated potassium conductance. The weak effects of ACh (20-200 microM) were considerably enhanced by addition of eserine (1-10 microM). All excitatory effects were completely antagonized by atropine (0.1-1 microM) but unaffected by dihydro-beta-erythroidine (DHBE) and gallamine (1-50 microM). In contrast to the muscarinic agonists, the nicotinic agonists nicotine and dimethylphenylpiperazinium (DMPP) had no excitatory effects on CA1 pyramidal cells. Phenyltrimethylammonium (PTMA), at high concentrations did depolarize cells and depress the AHP but these effects were antagonized by atropine and not DHBE or gallamine. The action of the analogue of cyclic GMP, 8-bromo-cyclic GMP, although variable, mimicked the membrane effects of ACh in some cells and depressed the AHP in most cells. Intracellular injection of cyclic GMP routinely depressed the AHP. In summary, we have demonstrated two cholinergic responses of hippocampal pyramidal cells that are mediated purely by muscarinic receptors. We could find no evidence to support a mixed-type receptor or the involvement of nicotinic receptors in the excitation of hippocampal pyramidal cells to cholinergic agents.

Characterization of a slow cholinergic post-synaptic potential recorded in vitro from rat hippocampal pyramidal cells.

Intracellular recording from CA1 pyramidal cells in the hippocampal slice preparation was used to compare the action of exogenously applied acetylcholine (ACh) and cholinomimetics to the effect of electrically stimulating sites in the slice known to contain cholinergic fibres. ACh depolarized pyramidal cells with an associated increase in input resistance, blocked a calcium-activated potassium conductance (GK(Ca], and blocked accommodation of action potential discharge. All of these actions were blocked by the muscarinic antagonist, atropine. Repetitive electrical stimulation of stratum (s.) oriens evoked a series of fast excitatory post-synaptic potentials (e.p.s.p.s) followed by an inhibitory post-synaptic potential. These potentials were followed by a slow e.p.s.p. that lasted 20-30 s. The slow e.p.s.p. was selectively enhanced by eserine and blocked by atropine. Ionophoretic application of ACh closely mimicked the time course of the slow e.p.s.p. The slow e.p.s.p. was blocked by tetrodotoxin and cadmium, indicating that it was dependent on propagated action potentials and on calcium. Considerably higher stimulus strengths were needed to elicit a slow e.p.s.p. than to elicit the earlier synaptic potentials. The size of the slow e.p.s.p. was markedly increased by repetitive stimulation. Stimulation of the alveus, s. oriens, s. pyramidale and fimbria all evoked a slow e.p.s.p., while stimulation of s. radiatum was relatively ineffective. The input resistance of the cell increased during the slow e.p.s.p. Hyperpolarizing the cell decreased the size of the slow e.p.s.p. and at membrane potentials of -70 mV or greater, little response was recorded. Stimulation of s. oriens blocked GK(Ca) and accommodation of action potential discharge. These effects, which could be seen in the absence of any change in membrane potential, were enhanced by eserine and blocked by atropine. The present electrophysiological results establish that CA1 pyramidal cells receive a cholinergic input and demonstrate that this input can dramatically alter the firing properties of these neurones for tens of seconds in the absence of any marked effect on membrane potential. Such an action contrasts with previously characterized synaptic potentials in this region of the brain.

Muscarinic inhibitory transmission in mammalian sympathetic ganglia mediated by increased potassium conductance.

Slow muscarinic inhibition may be a powerful influence on membrane properties in the peripheral and central nervous system. But the location of the muscarinic receptors in sympathetic ganglia, either on interneurones or on the postganglionic membrane, and the underlying mechanism of the inhibitory response, remains controversial. In mammalian sympathetic ganglia synaptic activation of muscarinic receptors located on inhibitory interneurones was thought to release catecholamines leading to a membrane hyperpolarization called the slow inhibitory postsynaptic potential, or s.-i.p.s.p.. However, the s.-i.p.s.p. in parasympathetic ganglia and in amphibian sympathetic ganglia is due to direct monosynaptic activation of muscarinic receptors, accompanied by an increased potassium conductance (but see ref. 11), and is not mediated by catecholamines. The situation is less clear in mammalian sympathetic ganglia and monosynaptic s.-i.p.s.ps observed in other ganglia could be exceptions to the hypothesis. We showed earlier that the s.-i.p.s.p. in rabbit superior cervical ganglia is not affected by catecholamine antagonists. We now show that the s.-i.p.s.p. in a mammalian sympathetic ganglion is due to the monosynaptic activation of muscarinic receptors, probably by an increase in potassium conductance.

Acetylcholine mediates a slow synaptic potential in hippocampal pyramidal cells.

The hippocampal slice preparation was used to study the role of acetylcholine as a synaptic transmitter. Bath-applied acetylcholine had three actions on pyramidal cells: (i) depolarization associated with increased input resistance, (ii) blockade of calcium-activated potassium responses, and (iii) blockade of accommodation of cell discharge. All these actions were reversed by the muscarinic antagonist atropine. Stimulation of sites in the slice known to contain cholinergic fibers mimicked all the actions. Furthermore, these evoked synaptic responses were enhanced by the cholinesterase inhibitor eserine and were blocked by atropine. These findings provide electrophysiological support for the role of acetylcholine as a synaptic transmitter in the brain and demonstrate that nonclassical synaptic responses involving the blockade of membrane conductances exist in the brain.

Comparison of the receptors mediating the catecholamine hyperpolarization and slow inhibitory postsynaptic potential in sympathetic ganglia.

We investigated the proposed catecholamine receptor in the superior cervical ganglion of the rabbit with the sucrose-gap technique to characterize the receptor pharmacologically. It has been suggested that this receptor is involved in the slow inhibitory postsynaptic potential in sympathetic ganglia. Epinephrine, norepinephrine and dopamine consistently hyperpolarized the ganglion membrane (N = 60). The order of potency was epinephrine greater than or equal to norepinephrine much greater than dopamine. Clonidine (10(-5) M), phenylephrine (10(-4) M) and isoproterenol (10(-3) M) also hyperpolarized the ganglion. However, apomorphine, even at millimolar concentration, did not hyperpolarize the membrane. The alpha antagonists phentolamine (10(-6) M) and yohimbine (10(-6) M) depressed the response to all catecholamines and shifted the catecholamine concentration-response curve to the right; dopamine and beta antagonists and the alpha-1 antagonist prazosin had no effect on the catecholamine hyperpolarizations. In contrast, the nerve-evoked slow inhibitory postsynaptic potential was selectively depressed only by atropine (10(-7) M). In conclusion, we characterized an alpha-2 adrenergic receptor in the rabbit superior cervical ganglion responsible for the catecholamine hyperpolarization and found that the slow inhibitory postsynaptic potential does not appear to be mediated by the same receptor.