The autopsy as a tool to monitor diagnostic error.
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Autopsy↗
Biomedical subjects
A Esteban
Publications and source records attributed to A Esteban.
A neurophysiological approach to brainstem reflexes. Blink reflex.
The blink reflex (BR) is a generalised phenomenon in mammals. Its teleological protective eye function is perhaps the reason why the BR can be provoked by a multitude of stimuli. As corneal and glabellar reflexes, BR has an inveterate use in the neurological exploration. Some of its physiopathological aspects were discussed more than 100 years ago, and soon half a century will have passed since the first electrophysiological study was published. This review focuses on the BR elicited by the electrical stimulation of the trigeminal supraorbital nerve, a controlled and reliable model in clinical neurophysiology. The electrically elicited BR is an exteroceptive-nociceptive reflex recorded on the orbicularis oculi muscle and formed by three components: the two principal ones, R1 and R2, of well-known characteristics, and a third, R3, of increasing interest, to which there is wide mention. The trigeminal afferent limb reaches the facial efferent one by means of a long and quite complex central pathway located at the brainstem bulbopontine level. The anatomical substrate and criteria of the rich topographical lesional semiology of the BR are established. The importance of the suprasegmental influences upon the reflex, coming mainly from the cerebral cortex and basal ganglia, as well as the impairment caused by their damage, will be emphasised. Special attention is paid to the relationship between the reflex and the dopaminergic system, and the consequences of its derangement. The methods of habituation and suppression-recovery of the BR are extensively and critically reviewed. These methods measure its excitability and serve in practice for the pathophysiological study of numerous diseases. The relationship of the BR with the spontaneous blinking is considered, and the existence of a primary inhibitory reflex on levator palpebrae muscles, previous to the active reflex response of the orbicularis, is proposed. The electrophysiological characteristics of the glabellar reflex, the corneal reflex, the acoustic, photic and somatosensory provoked BR, the ontogeny, and some of the common factors influencing the reflex, such as sleep, are also discussed. The strategic position of the neural structures of the BR, in an area involved in the gating of the various sensory-motor systems and the relative ease to its evaluation with common methodology used in clinical neurophysiology, makes the BR an essential tool for the diagnosis and pathophysiological insight into an important number of human neurological disorders.
Animals↗
Modulation of systemic hemodynamics by exogenous L-arginine in normal and bacteremic sheep.
OBJECTIVE: To investigate whether exogenous L-arginine, the substrate for nitric oxide synthase, modulates systemic hemodynamics in sepsis. DESIGN: Prospective, controlled study in a sheep model of sepsis. SETTING: Animal research facility in a university hospital. SUBJECTS: Adult sheep weighing between 35 and 55 kg. INTERVENTIONS: Adult sheep sedated and mechanically ventilated, were monitored with a pulmonary arterial catheter and an ileal tonometer. Four groups of sheep were studied: nonseptic, septic, nonseptic treated with L-arginine, and septic treated with L-arginine. Sepsis was induced by the intravenous administration of Escherichia coli (1.5x10(8) colony-forming units/kg for 30 mins). L-arginine was administered as an intravenous bolus (200 mg/kg for 10 mins) before the septic challenge followed by 200 mg/kg/hr for 300 mins. MEASUREMENTS AND MAIN RESULTS: Sepsis induced a state of acidosis, hyperlactatemia, hypoxemia, and gastric intramucosal acidosis. During the first 30 mins after the septic challenge, there was a decrease in cardiac index and blood pressure, and an increase in systemic vascular resistance. Thereafter, blood pressure returned to baseline values, and systemic vascular resistance fell. Treatment with L-arginine in nonseptic sheep did not induce any biochemical or hemodynamic effect. In septic sheep, treatment with L-arginine was associated with a greater increase in systemic vascular resistance during the first 30 mins, and a more marked decrease in blood pressure and systemic vascular resistance after 180 mins. CONCLUSIONS: Exogenous administration of L-arginine does not induce hemodynamic effects in normal animals, exacerbates the acute vasoconstriction associated with the intravenous infusion of E. coli and potentiates the sepsis-induced vasodilation. Our results suggest that a) nitric oxide production is not constitutively modulated by exogenous L-arginine, b) L-arginine probably enhances the sepsis-induced sympathetic discharge, and c) L-arginine becomes rate-limiting for the formation of nitric oxide at approximately 3 hrs after the initiation of the septic challenge.
Acidosis↗
Unmasking of the trigemino-accessory reflex in accessory facial anastomosis.
OBJECTIVE: To evaluate the possible blink reflex responses in facial muscles reinnervated by the accessory nerve. METHOD: Eleven patients with a complete facial palsy were submitted to a surgical repair by an accessory facial nerve anastomosis (AFA). In this pathological group, blink reflex was studied by means of percutaneous electrical stimulation of the supraorbital nerve and recording from the orbicularis oculi muscle. A control group comprised seven normal people and seven patients with a complete Bell's facial palsy; in this group, responses on the sternocleidomastoideus (SCM) muscles were studied after supraorbital nerve stimulation. RESULTS: All the patients with AFA showed a consistent degree of facial reinnervation. Ten out of the 11 patients with AFA showed reflex responses; in six, responses were configured by a double component pattern, resembling the R1 and R2 components of the blink reflex; three patients had an R1-like response and one patient showed a unique R2 component. Mean values of latencies were 15.2 (SD 4.6) ms for the R1 and 85.3 (SD 9.6) ms for the R2. In the control group, eight out of 14 people had evidence of reflex responses in the SCM muscles; these were almost exclusively configured by a bilateral late component (mean latency 63.5 (SD15.9) ms) and only one of the subjects showed an early response at 11 ms. CONCLUSION: The trigemino-accessory reflex response in the pathological group was more complex and of a significantly higher incidence than in the control group. These differences could be tentatively explained by a mechanism of synaptic plasticity induced by the impairment of the efferent portion of the reflex. This could unmask the central linking between the trigeminal and the accessory limbs of the reflex. The findings described could be a demonstration of neurobionomic function in the repairing process of the nervous system.
Accessory Nerve↗
Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation. Spanish Lung Failure Collaborative Group.
The duration of spontaneous breathing trials before extubation has been set at 2 h in research studies, but the optimal duration is not known. We conducted a prospective, multicenter study involving 526 ventilator-supported patients considered ready for weaning, to compare clinical outcomes for trials of spontaneous breathing with target durations of 30 and 120 min. Of the 270 and 256 patients in the 30- and 120-min trial groups, respectively, 237 (87.8%) and 216 (84.8%), respectively, completed the trial without distress and were extubated (p = 0.32); 32 (13.5%) and 29 (13.4%), respectively, of these patients required reintubation within 48 h. The percentage of patients who remained extubated for 48 h after a spontaneous breathing trial did not differ in the 30- and 120-min trial groups (75.9% versus 73.0%, respectively, p = 0.43). The 30- and 120-min trial groups had similar within-unit mortality rates (13 and 9%, respectively) and in-hospital mortality rates (19 and 18%, respectively). Reintubation was required in 61 (13.5%) patients, and these patients had a higher mortality (20 of 61, 32.8%) than did patients who tolerated extubation (18 of 392, 4.6%) (p < 0.001). Neither measurements of respiratory frequency, heart rate, systolic blood pressure, and oxygen saturation during the trial, nor other functional measurements before the trial discriminated between patients who required reintubation from those who tolerated extubation. In conclusion, after a first trial of spontaneous breathing, successful extubation was achieved equally effectively with trials targeted to last 30 and 120 min.
Aged↗
A randomized and controlled trial of the effect of treatment aimed at maximizing oxygen delivery in patients with severe sepsis or septic shock.
OBJECTIVE: To evaluate the effects of increased oxygen delivery on mortality and morbidity. DESIGN: Randomized, controlled trial. SETTING: Medical-surgical ICU of a tertiary care hospital. PATIENTS: Sixty-three patients classified according to predetermined criteria as having severe sepsis or septic shock. INTERVENTIONS: The patients were randomly assigned to one of two groups: the control group (n = 32) received conventional therapy with a normal targeted value of oxygen delivery, and the treatment group (n = 31) received therapy with a targeted oxygen delivery index (DO2I) value of > 600 mL/min/m2. The therapeutic approach to maintain BP, arterial saturation, hemoglobin concentration, and pulmonary artery occlusion pressure was similar in both groups. MEASUREMENTS AND MAIN RESULTS: The hemodynamic, oxygen transport, and gastric intramucosal pH measurements were recorded at the time of admission to the study and every 6 h for the next 96 h. The outcome measures were the rate of patient mortality and the number of organ dysfunctions occurring during the ICU stay. The study groups were similar with respect to demographics and admission hemodynamic variables, but the percentage of patients with positive blood cultures was significantly higher in the control group than in the treatment group, respectively: 34 vs 13% (p = 0.04). The average cardiac index was significantly higher in the treatment group than in the control group, respectively: 3.96 vs 3.05 L/min/m2 (p = 0.01). This factor did not significantly affect the DO2I. Nine of the 31 treatment group patients reached an average DO2I value of > 600 mL/min/m2. The rate of mortality in the control group patients up to the time of ICU discharge (66%) was similar to that seen in the treatment group (74%), respectively: 21 of 32 vs 23 of 31 (p = 0.46). The number of dysfunctional organs per patient was also similar in the control and treatment groups, respectively: 2.1+/-1.1 vs 2.6+/-1.2 (p = 0.12). CONCLUSION: Treatment aimed at maximizing oxygen delivery in patients with severe sepsis or septic shock does not reduce mortality or morbidity.
Aged↗
Comparison of in vitro effects of triflusal and acetysalicylic acid on nitric oxide synthesis by human neutrophils.
Recent studies have suggested that the protective anti-ischemic effects of acetylsalicylic acid are stronger than the inhibition of platelet thromboxane A2 synthesis. Since ischemic events still occur in acetylsalicylic acid-treated patients, the development of new drugs with more powerful protective effects is needed. We compared the effects of a new platelet antiaggregating drug, 2-acetoxy-4-trifluoromethyl-benzoic acid (triflusal) and of acetylsalicylic acid on the interaction between human neutrophils and platelets, examining the capability of neutrophils to generate nitric oxide (NO). Triflusal, in the presence of neutrophils, showed a greater antiplatelet potency than acetylsalicylic acid to inhibit thrombin-induced platelet activation. Significant stimulation of NO-mediated mechanisms in the presence of acetylsalicylic acid or triflusal was demonstrated by the following findings: (1) increased metabolism of arginine to citrulline, (2) increase of cGMP in the platelet/neutrophil system and (3) the inhibitory action of the L-arginine (L-Arg) competitive analogue, NG-nitro-L-arginine-methyl ester (L-NAME), which was reversed by L-Arg. Triflusal increased the stimulation of NO synthesis by neutrophils more than did of acetylsalicylic acid. The main metabolite of triflusal, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB), alone or in combination with acetylsalicylic acid, did not modify NO production by neutrophils. Therefore, the whole molecule of triflusal is needed to stimulate NO production by neutrophils. Our results show that, in the presence of neutrophils, triflusal exerts an antiplatelet effect greater than that of acetylsalicylic acid, demonstrating a more powerful stimulation of the NO/cGMP system. The present results indicate that it is possible to develop new and more potent acetylsalicylic acid-related antiplatelet drugs for the prevention of the myocardial ischemic/reperfusion processes.
Aspirin↗
Degree of hypercoagulability and hyperfibrinolysis is related to organ failure and prognosis after burn trauma.
Severely burned patients often present a hypercoagulability situation. However, its magnitude, time course, and relationship with organ failure and outcome remains to be established. Forty-three patients were studied on the first and seventh day after burn for hypercoagulability and fibrinolysis parameters. A hypercoagulability and hyperfibrinolysis state was found the first day after burn demonstrated by high levels of activated factor VII (VIIa, p<0.01), thrombin-antithrombin III complex (TAT, p<0.01), tissue plasminogen activator (t-PA, p<0.001) and D dimer (DD, p<0.01) and low levels of antithrombin III (ATIII, p<0.01), protein C (PC, p<0.01), plasminogen (PG, p<0.001) and alpha2 antiplasmin (AP, p<0.001). A paradoxical coexisting hypofibrinolysis was found as suggested by a low global fibrinolytic activity in the euglobulin plasma fraction fibrin plate assay (FA, p<0.01) and high levels of tissue plasminogen activator inhibitor type 1 (PAI-1, p<0.01). On day 7, a less marked hypercoagulability situation was found, with low ATIII (p<0.01) and PC (p<0.01), persisting the hypofibrinolytic situation observed on the first day. Non-survivors (NS) showed higher levels of VIIa (p<0.01), TAT (p<0.05) and t-PA (p<0.05), and lower levels of ATIII (p<0.05), PC (p<0.05) and AP (p<0.001) than survivors (S) on the first day. Also, there was a positive correlation of Marshall organ failure score with ATIII, (r2=0.49, p<0.001), PC, (r2=0.14, p<0.045) and PG levels, (r2=0.41, p<0.0003). Severely burned patients show a state of transient disseminated intravascular coagulation, related to the development of organ failure and outcome.
Adult↗
Stiff-man syndrome in a child.
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Autoantibodies↗
Clinical management of weaning from mechanical ventilation.
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Algorithms↗
Weaning from mechanical ventilation in pediatric intensive care patients.
OBJECTIVE: The development of weaning predictors in mechanically ventilated children has not been sufficiently investigated. The purpose of this study was to evaluate the accuracy of some weaning indices in predicting weaning failure. DESIGN: Prospective, interventional study. SETTING: University-affiliated children's hospital with a 19-bed intensive care unit. PATIENTS: 84 consecutive infants and children requiring mechanical ventilation for at least 48 h and judged ready to wean by their primary physicians. INTERVENTIONS: Patients who met the criteria to start weaning underwent a trial of spontaneous breathing lasting up to 2 h. Bedside measurements of respiratory function were obtained immediately before discontinuation of mechanical ventilation and within the first 5 min of spontaneous breathing. The primary physicians were blinded to those measurements, and the decision to extubate a patient at the end of the spontaneous breathing trial or reinstitute mechanical ventilation was made by them. Failure to wean was defined as the requirement for mechanical ventilation at any time during the trial of spontaneous breathing (trial failure) or needing reintubation within 48 h of extubation (extubation failure). MEASUREMENTS AND MAIN RESULTS: Seventy-five patients had neither signs of respiratory distress nor deterioration in gas exchange during the trial and were extubated. Twelve patients required reintubation within 48 h. In 9 patients, mechanical ventilation was reinstituted after a median duration of the spontaneous breathing trial of 35 min. The only independent predictor of trial failure was tidal volume indexed to body weight [odds ratio 2.60, 95 % confidence interval (CI) 1.40 to 24.9]. The only independent predictor of extubation failure was frequency-to-tidal volume ratio indexed to body weight (odds ratio 1.23, 95 % CI 1.11 to 1.36). The sensitivity, specificity, and positive and negative predictive values to predict weaning failure were calculated for each of the above variables. These values were 0.48, 0.86, 0.53, and 0.83, respectively, for a frequency-to-tidal volume ratio higher than 11 breaths/min per ml per kg and 0.43, 0.94, 0.69, and 0.83, respectively, for a tidal volume lower than 4 ml/kg. CONCLUSIONS: Three-quarters of ventilated children can be successfully weaned after a trial of spontaneous breathing lasting 2 h. Both tidal volume and frequency-to-tidal volume ratio indexed to body weight were poor predictors of weaning failure in the study population.
Body Weight↗
The balance between oxygen supply and demand in the intestine can be assessed by measuring the difference between arterial and intramucosal PCO2 (P[t-a]CO2), estimated by means of a gastric tonometer.
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Adult↗
[Palpebral ptosis and blepharospasm secondary to hemispheric cerebral infarction].
A case that combines cerebral eyelid ptosis and blepharospasm secondary to cerebral hemisphere infarction is shown. EMG recording from the facial and eyelid muscles revealed lack of the levator palpebrae superioris, orbicularis oculi and corrugator muscles activity. Any voluntary opening attempt lead to a simultaneous contraction of the three muscles. Blink reflex responses were normal although showed facilitation features on the right side and mild inhibition characteristics from the left side. Median nerve SEP revealed a loss of precentral components (P22-N30) as well as a delay and amplitude decrease of N20. Transcranial magnetic stimulation disclosed a complete lesion of corticospinal pathway for right upper limb. In this case, a right hemisphere lesion caused an unusual eyelid motor abnormality: cerebral eyelid ptosis and blepharospasm induced by the voluntary eyelid opening.
Aged↗
[Lateral femoral cutaneous neuropathy: paresthetic meralgia. Neurophysiological diagnosis].
INTRODUCTION: The neurophysiological approach to meralgia paresthetica (MP) deals with the possible abnormalities demonstrated in the peripheral nerve conduction and/or somatosensory evoked potentials (SEP) of the lateral femoral cutaneous nerve (LFCN). MATERIAL AND METHODS: To ascertain the diagnostic value of these methods, a group of 23 patients with unilateral MP symptoms has been studied; SEP of LFCN was also evaluated in a series of normal people. RESULTS: LFCN conduction was abnormal on the symptomatic side in 47.6% of the cases and nerve potential was absent on both sides in all the rest. SEPLFCN showed some impairment in 91% of the cases on the symptomatic side and responses were obtained on the asymptomatic side in every case; the most common abnormality was the delay of the response followed by its followed by its absence. In the normal group, the amplitude of potentials registered on the contralateral scalp to the stimulated side was usually higher than that registered on the median line, where they eventually lacked. Methodologically, this fact supports the need of a multiple recording of the SEPLFCN on the scalp. CONCLUSIONS: The SEPLFCN should be considered as the main technique for the objective diagnosis of MP and although LFCN conduction can supply useful information in individual cases, its exclusive use may lead to rather many positive false results.
Evoked Potentials, Somatosensory↗
Extubation outcome after spontaneous breathing trials with T-tube or pressure support ventilation. The Spanish Lung Failure Collaborative Group.
A 2-h T-tube trial of spontaneous breathing was used in selecting patients ready for extubation and discontinuation of mechanical ventilation. However, some doubt remains as to whether it is the most appropriate method of performing a spontaneous breathing trial. We carried out a prospective, randomized, multicenter study involving patients who had received mechanical ventilation for more than 48 h and who were considered by their physicians to be ready for weaning according to clinical criteria and standard weaning parameters. Patients were randomly assigned to undergo a 2-h trial of spontaneous breathing in one of two ways: with a T-tube system or with pressure support ventilation of 7 cm H2O. If a patient had signs of poor tolerance at any time during the trial, mechanical ventilation was reinstituted. Patients without these features at the end of the trial were extubated. Of the 246 patients assigned to the T-tube group, 192 successfully completed the trial and were extubated; 36 of them required reintubation. Of the 238 patients in the group receiving pressure support ventilation, 205 were extubated and 38 of them required reintubation. The percentage of patients who remained extubated after 48 h was not different between the two groups (63% T-tube, 70% pressure support ventilation, p = 0.14). The percentage of patients falling the trial was significantly higher when the T-tube was used (22 versus 14%, p = 0.03). Clinical evolution during the trial was not different in patients reintubated and successfully extubated. ICU mortality among reintubated patients was significantly higher than in successfully extubated patients (27 versus 2.6%, p < 0.001). Spontaneous breathing trials with pressure support or T-tube are suitable methods for successful discontinuation of ventilator support in patients without problems to resume spontaneous breathing.
Aged↗
Abnormalities in the metabolism of acetaminophen in patients infected with the human immunodeficiency virus (HIV).
The urinary concentration of acetaminophen and its glucuronide, sulphate, cysteine, and mercapturate conjugates was measured by high-performance liquid chromatography in 32 healthy volunteers, 9 untreated symptom-free HIV-seropositive subjects, and 19 patients with AIDS after a single oral dose of 1.5 g of acetaminophen. The concentration of the glucuronide conjugate was significantly lower in AIDS patients when simultaneously compared with concentrations found in healthy individuals and symptoms-free HIV-seropositive subjects. Differences between healthy volunteers and symptom-free HIV seropositives were not encountered. By contrast, urinary concentrations of sulphate and oxidation pathway-derived metabolites were significantly higher in AIDS patients as compared with the other two groups. When AIDS patients treated with zidovudine were compared with those not given this medication, differences in the urinary excretion of acetaminophen and its metabolites were not observed. However, the urinary concentration of mercapturic acid was significantly higher in those given enzyme inducers, such as rifampicin or phenytoin, than in AIDS patients not treated with these drugs. In summary, patients with advanced HIV infection showed reduced acetaminophen glucuronidation and increased formation of the hepatotoxic oxidation metabolites, which was independent of zidovudine therapy.
Acetaminophen↗
Supranuclear palsy of voluntary eyelid closure: electrophysiological correlate.
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Blinking↗
Selective allergic reaction to oral cloxacillin.
BACKGROUND: Previous observations indicate that in some instances subjects allergic to penicillins may experience an allergic reaction after taking the drug by one route but have good tolerance after being administered the same drug by a different route. OBJECTIVE: The purpose was to establish if cloxacillin (CLX) induced a selective response only after oral route administration in a suspected case and to study if there were differences between the oral and parenteral formulations. METHODS: Skin tests were carried out using benzylpenicillin (BP) conjugated to poly-L-lysine (BPO-PLL), minor determinant mixture of benzylpenicillin (MDM), ampicillin (AMP), amoxicillin (AX) and cloxacillin (CLX). Radioallergosorbent assay (RAST) was carried out using BPO-PLL, AX-PLL and CLX-PLL sensitized discs. In the case the skin tests and RAST were negative, a controlled challenge administering the drug by both oral and parenteral route was made. Urine samples were taken at prechallenge (basal levels) and at three periods after challenge (1-3, 3-6 and 6-9 h). Analysis of oral and parenteral formulations was made by HPLC chromatography. RESULTS: All skin tests and RASTs were negative. With the challenge tests the patient tolerated parenteral BP and oral phenoxymethyl penicillin (PV) and oral and parenteral AMP up to therapeutic concentrations. Parenteral CLX (500 mg) was also tolerated but 30 min after administering 50 mg by the oral route progressive generalized erythema with pruritus, facial angioedema and tachycardia developed. Urine samples taken during the challenge tests showed an increased excretion of N-methyl histamine (N-MH) 3 h after challenge with oral CLX but no change in N-MH levels after challenge with parenteral CLX or the other penicillins, indicating that histamine was released during the allergic episode with oral CLX. HPLC analysis of the oral and parenteral CLX formulations indicated that there were no differences and that neither polymers no other contaminant materials were present. CONCLUSION: Although the nature of the allergenic determinant involved in the induction of the reaction is not yet known, the oral route may have favoured the production of a metabolite not generated by the parenteral route.
Administration, Oral↗