Clipping vs. coiling in acute aneurysmal subarachnoid haemorrhage: Should the patient's medical condition influence treatment modality?

INTRODUCTION: Acute subarachnoid haemorrhage (SAH) resulting from aneurysmal rupture is a medical condition associated with significant morbidity and mortality. Medical complications resulting from the bleeding itself, along with the patient's underlying medical conditions are known to represent possible prognostic factors in acute SAH. However, their respective significance on the patient's overall clinical outcome following either endovascular coiling (EC) or surgical clipping (SC) remains to be ascertained as well as their potential role in choosing a definitive treatment option. We thus reviewed the evidence concerning the patient's medical condition as a factor in this decision making process. METHODOLOGY: Source data were obtained from a MEDLINE search of the medical literature and by manual review of published randomised trials comparing EC to SC. RESULTS: The last three decades allowed for detection of medical complications with increasing frequency in the context of SAH, as awareness for them has improved. Despite the fact that a patient's extra-neurological condition can be a significant prognostic factor after a SAH, our review demonstrates that medical conditions in general were not taken into consideration in randomized trials comparing EC to SC. Also, we found no analysis comparing the potential role of prior versus post-SAH medical conditions in choosing either therapeutic avenue. CONCLUSION: It is not determined whether it is appropriate for SAH patients to be offered treatment for a ruptured aneurysm based mostly on anatomical criteria or if, within certain subgroups of patients, EC and SC should also be recommended in light of what the patient can tolerate from a medical standpoint. Although we hypothesize that in practice, the patient's medical condition is considered in the decision making process, it remains to be documented. Patient, aneurysm and institution-related factors are all interrelated, as is patient care. Data on all of these factors are thus needed and their analysis by association rather than by dissociation may be the key in answering our question.

Respiratory rhythms generated in the lamprey rhombencephalon.

Brainstem networks generating the respiratory rhythm in lampreys are still not fully characterized. In this study, we described the patterns of respiratory activities and we identified the general location of underlying neural networks. In a semi-intact preparation including the brain and gills, rhythmic discharges were recorded bilaterally with surface electrodes placed over the vagal motoneurons. The main respiratory output driving rhythmic gill movements consisted of short bursts (40.9+/-15.6 ms) of discharge occurring at a frequency of 1.0+/-0.3 Hz. This fast pattern was interrupted by long bursts (506.3+/-174.6 ms) recurring with an average period of 37.4+/-24.9 s. After isolating the brainstem by cutting all cranial nerves, the frequency of the short respiratory bursts did not change significantly, but the slow pattern was less frequent. Local injections of a glutamate agonist (AMPA) and antagonists (6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or D,L-amino-5-phosphonopentanoic acid (AP5)) were made over different brainstem regions to influence respiratory output. The results were similar in the semi-intact and isolated-brainstem preparations. Unilateral injection of AP5 or CNQX over a rostral rhombencephalic region, lateral to the rostral pole of the trigeminal motor nucleus, decreased the frequency of the fast respiratory rhythm bilaterally or stopped it altogether. Injection of AMPA at the same site increased the rate of the fast respiratory rhythm and decreased the frequency of the slow pattern. The activity recorded in this area was synchronous with that recorded over the vagal motoneurons. After a complete transverse lesion of the brainstem caudal to the trigeminal motor nucleus, the fast rhythm was confined to the rostral area, while only the slow activity persisted in the vagal motoneurons. Our results support the hypothesis that normal breathing depends on the activity of neurons located in the rostral rhombencephalon in lampreys, whereas the caudal rhombencephalon generates the slow pattern.

Anatomical and physiological study of respiratory motor innervation in lampreys.

The innervation of gill muscles of lampreys was investigated in a semi-intact preparation in which the respiratory rhythm was maintained for more than 2 days. Lesion experiments showed that the muscles of gill 1 are innervated by nerves VII (facial) and IX (glossopharyngeal), and those of gill 2 by nerve IX and the first branchial branch of nerve X (vagal). The other gills are supplied by the other branchial branches of nerve X. Retrograde tracers, injected in peripheral respiratory nerves, showed that branchial muscles are innervated by VII, IX and X motoneurons. Within the X nucleus, the motoneuron pools were branchiotopically organized, but with considerable rostro-caudal overlap. Electrophysiological recordings were used to show that the onset of activation of the branchial muscles was increasingly delayed with the distance from the brainstem, but that motoneuronal activity recorded with surface electrodes began at approximately the same time in all pools. The conduction velocity of VII and caudal X motor axons was found to be the same. Differences in the length of motoneuron axons appear to account for the rostro-caudal delay in gill contraction. The data presented here provide a much needed anatomical and physiological basis for further studies on the neural network controlling respiration in lampreys.

Treating neuropathic incontinence in children with seromuscular colocystoplasty and an artificial urinary sphincter.

PURPOSE: To review the results of artificial urinary sphincter (AUS) implantation combined with seromuscular colocystoplasty (SCLU) in the treatment of mixed neurogenic urinary incontinence in children. PATIENTS AND METHODS: Patients (27, six females) who had undergone SCLU were interviewed, and their charts and imaging studies reviewed retrospectively. Their urodynamic data were analysed and bladder capacity, end-filling pressure, safe capacity and percentage of expected capacity for age compared before and after surgery. Continence was defined as dryness between catheterizations or voiding with no need for protective pads. RESULTS: The mean (sd) follow-up since the SCLU was 1.7 (1.1) years; continence was achieved in 24 of the 27 (89%) patients with no additional procedures. No significant upper tract changes developed. Bladder capacity, safe capacity for age and end-filling pressure were all improved significantly. There were two AUS erosions necessitating removal and in one patient the augmentation failed. Six patients early in the series developed an 'hourglass' deformity that required correction. Modifications to the technique to avoid this complication are discussed. CONCLUSIONS: For children with neuropathic incontinence who require both augmentation of outlet resistance and bladder storage capacity, the combination of the AUS and SCLU effectively achieves continence with no upper tract deterioration. SCLU is also the preferred method of augmentation when adverse bladder changes occur after implanting the AUS.

Mechanism of Kex2p inhibition by its proregion.

Many proteases are produced as zymogens bearing an N-terminal proregion acting both as intramolecular chaperone and as enzyme inhibitor. We studied here the inhibition mechanism of the yeast proprotein convertase Kex2p by its proregion. A recombinant secreted and soluble form of Kex2p was produced in Pichia pastoris and its enzymatic properties toward a fluorogenic synthetic peptide were characterized. Recombinant Escherichia coli-produced Kex2p proregion specifically and potently inhibited the enzyme, with an IC(50) of 160 nM. Exploration of the inhibition mechanism revealed that the proregion behaved as a mixed inhibitor.

Inhaled prostacyclin (PGI2) is an effective addition to the treatment of pulmonary hypertension and hypoxia in the operating room and intensive care unit.

PURPOSE: There is a growing interest in the intraoperative and intensive care use of inhaled epoprostenol (PGI2) for the treatment of pulmonary hypertension (PHT) and hypoxia of cardiac or non-cardiac origin. We report our experience with this form of therapy. METHODS: A retrospective chart review of all patients who received inhaled PGI2 over a one-year period was undertaken. Demographic, hemodynamic, oxygenation status, mode of administration, side effects, duration of hospital stay, and mortality were noted. RESULTS: Thirty-five patients, of which 33 (92%) were in the intensive care unit, received inhaled PGI2. Of the 27 patients whose pulmonary artery pressure (PAP) was monitored, a significant decrease in mean PAP from 34.8 +/- 11.8 mmHg to 32.1 +/- 11.8 mmHg was observed within one hour after the start of therapy (P=0.0017). Selective pulmonary vasodilatation occurred in 77.8% of the patients. Thirty-three patients had arterial blood gases before and after therapy. There was an improvement in the PaO2/FIO2 ratio in 88% of these with a 175% improvement on average. The ratio of PaO2/FIO2 improved from 108 +/- 8 to 138 +/- 105 (P=0.001). Six patients (17%) presented hypotension, two had subsequent pneumothorax, one had bronchospasm and in one patient PGI2 inhalation was stopped because of increasing peak pulmonary pressures from the secondary flow coming from the nebulizer. Mortality of the cohort was 54%. CONCLUSION: Inhaled PGI2 can be useful in the treatment of patients with PHT and severe hypoxia. It can however be associated with systemic side effects.

Myocardial perfusion imaging findings and the role of adenosine in the warm-up angina phenomenon.

OBJECTIVES: This study examined the roles of myocardial perfusion and adenosine in warm-up angina. BACKGROUND: In warm-up angina, neither the role of an adenosine-mediated mechanism, as is found in experimental ischemic preconditioning, nor of increased myocardial perfusion is well defined. METHODS: In substudy A, a single-photon emission computed tomography (SPECT)-thallium-201 exercise test was performed by 12 subjects with ischemic heart disease on three occasions one week apart. The third test was preceded by a warm-up test. The extent of the thallium deficit and its intensity on the third test were compared with the baseline tests controlling for the heart rate-systolic blood pressure product (RPP) at thallium injection. In substudy B, 12 similar subjects did two successive exercise tests at two separate sessions and received the adenosine antagonist, aminophylline (intravenous 5 mg/kg bolus and 0.9 mg/kg/h infusion) at one session, and equivalent saline at the other session. Change in ischemic threshold (RPP at 1 mm ST segment depression) and in maximum ST depression adjusted for RPP were analyzed. RESULTS: In substudy A, despite a significant attenuation of electrocardiogram indexes of myocardial ischemia between the baseline and third (warmed-up) tests, the thallium extent deficits (20.8 +/- 15.1% and 16.8 +/- 12.4%) and intensity deficits (41.2 +/- 12.6% and 39.3 +/- 12.6%) did not differ significantly. In substudy B, the increase in ischemic threshold on re-exercise was unaffected by aminophylline. Adjusted maximum ST depression even decreased to a greater extent on re-exercise with aminophylline (by 51 +/- 21%) than with saline (by 32 +/- 19%) (p = 0.012). CONCLUSIONS: While warm-up angina is associated with a significant attenuation of exercise electrocardiogram indexes of ischemia, it is unaccompanied by significant changes in SPECT perfusion and does not appear to be mediated by an adenosine-dependent mechanism since it is not blocked by aminophylline. Thus, its mechanism, which appears distinct from experimental ischemic preconditioning, remains unidentified.

Acute respiratory distress syndrome: 30 years later.

Acute respiratory distress syndrome (ARDS) was first described about 30 years ago. Modern definitions and statements have recently been proposed to describe ARDS accurately, but none is perfect. Diffuse alveolar damage is the basic pathological pattern most commonly observed in ARDS, and the term includes permeability edema. The alveolar epithelium of the alveolar-capillary barrier is clearly a key component requiring repair, given its multipotent functional activity. Lung inflammation and neutrophil accumulation are essential markers of disease in ARDS, and a wide variety of pro- and anti-inflammatory cytokines have been described in the alveolar fluid and blood of patients. These molecules still have to prove their value as diagnostic or prognostic biomarkers of ARDS. Supportive therapy in ARDS improved in the past decade; mechanical ventilation with lung protective strategies and patient positioning are gaining interest, but the indications for corticosteroids for ARDS are still debated. Nitric oxide may have a place in the treatment of one-third of patients. Novel approaches, such as surfactant replacement and liquid ventilation, may further improve supportive therapy. Innovative interventions may be on the horizon in treatments that help to resolve or modulate common pathways of ARDS, such as inflammation (eg, granulocyte-colony stimulating factor) or epithelial repair (eg, keratinocyte growth factor).

Inhaled nitric oxide in acute respiratory distress syndrome: a pilot randomized controlled study.

This pilot randomized controlled clinical trial of patients with ARDS was implemented to study the impact of inhaled nitric oxide (inhNO) on lung function, morbidity, and mortality. Thirty patients with ARDS were randomly allocated to usual care or usual care plus inhNO. The optimal dose of inhNO was determined to be between 0.5 and 40 parts-per-million daily. All therapeutic interventions were standardized. ARDS resulted mainly from sepsis (25 of the 30). During the first 24 h, the hypoxia score increased greatly in patients treated with inhNO +70.4 mm Hg (+59%) versus +14.2 mm Hg (+9.3%) for the control group (p = 0.02), venous admixture decreased from 25.7 to 15.2% in the inhNO group, and from only 19.4 to 14.9% in the control group (p = 0.05). After the first day of therapy no further beneficial effect of inhNO was detected. Forty percent of the patients treated with inhNO were alive and weaned from mechanical ventilation within 30 d after randomization compared with 33.3% in the control group (p = 0.83). The 30-d mortality rate was similar in the two groups; most deaths (11 of 17) were due to multiple organ dysfunction syndrome. This study shows that inhNO, in this population, may improve gas exchange but does not affect mortality.

A reappraisal of exercise electrocardiographic indexes of the severity of ischemic heart disease: angiographic and scintigraphic correlates.

OBJECTIVES: We explored how the exercise electrocardiographic (ECG) indexes generally presumed to signify severe ischemic heart disease (IHD) correlate with coronary angiographic and scintigraphic myocardial perfusion findings. BACKGROUND: In exercise testing, it is generally assumed that the early onset of ST segment depression and its occurrence at a low rate-pressure product (ischemic threshold); the amount of maximal ST segment depression; and a horizontal or downsloping ST segment and its prolonged recovery after exercise signify more severe IHD. However, the relation of these indexes to coronary angiographic and exercise myocardial perfusion findings in patients with IHD is unclear. METHODS: We prospectively carried out a symptom-limited 12-lead Bruce protocol thallium-201 single-photon emission computed tomographic (SPECT) exercise test in 66 consecutive subjects with stable angina, > or = 70% stenosis of at least one coronary artery, normal rest ECG and left ventricular wall motion and a prior positive exercise ECG. The above ECG indexes, vessel disease (VD), a VD score and the quantitative thallium-SPECT measures of the extent, maximal deficit and redistribution gradient of the perfusion abnormality were characterized. RESULTS: Maximal ST segment depression could not differentiate the number of diseased vessels; was not related to VD score, maximal thallium deficit or redistribution gradient; but was related to the extent of perfusion abnormality (r = 0.29, 95% confidence interval [CI] 0.08 to 0.52, p = 0.02). Time of onset of ST segment depression correlated inversely only with VD (r = -0.22, 95% CI -0.44 to -0.05, p < 0.05), whereas the ischemic threshold had low inverse correlation only with VD score (r = -0.25, 95% CI -0.47 to -0.01, p < 0.05) and the redistribution gradient (r = -0.33, 95% CI -0.53 to -0.10, p < 0.01). A horizontal or downsloping compared with an upsloping ST segment did not demonstrate more severe angiographic and scintigraphic disease. Recovery time did not correlate with angiographic and scintigraphic findings, and correlations between angiographic and scintigraphic findings were also low or absent. CONCLUSIONS: In this homogeneous study group, the exercise ECG indexes did not necessarily signify more severe IHD by angiographic and scintigraphic criteria. Lack of concordance between the exercise ECG, angiography and myocardial scintigraphy suggests that these diagnostic modalities examine different facets of myocardial ischemia, underscoring the need for caution in the interpretation of their results.

Intrauterine diagnosis of cytomegalovirus and rubella infections by amniocentesis.

OBJECTIVE: To establish a correlation between the presence of cytomegalovirus (CMV) or rubella virus in amniotic fluid obtained through amniocentesis and fetal infection. DESIGN: Case series. SETTING: Five hospitals in the Montreal region. Virology testing was done at the Virology Research Centre, Institut Armand-Frappier, Laval, Que. PATIENTS: Thirteen pregnant women infected with CMV, 3 with rubella, their 15 babies and 2 fetuses. Twelve of the women with CMV infection were recruited from a prospective study of CMV infection in pregnancy. Infection in the other women was detected through routine laboratory diagnostic testing. INTERVENTION: Amniotic fluid samples were cultured for CMV and rubella virus. Congenital infection of the neonates was established through isolation of either virus from pharyngeal mucus and urine specimens collected during the first 3 days of life or from fetal tissue if the pregnancy was terminated. MAIN RESULTS: CMV was cultured from the amniotic fluid of three of the CMV-infected women and from the pharyngeal mucus and urine specimens of their infants. Of the three women with rubella the amniotic fluid of one (who had a twin pregnancy) was positive for rubella virus. After the in-utero death of one fetus she underwent a therapeutic abortion of both. Examination of fetal tissue indicated that both fetuses had been infected with rubella virus. Each of the two other women with rubella gave birth to an uninfected, healthy infant. CONCLUSIONS: We found a strong correlation between the isolation of CMV or rubella virus from the amniotic fluid and the presence of congenital infection. This suggests that amniocentesis used to detect the presence of a virus is a useful method for the diagnosis of fetal infection.

Effect of synchronous increase in intrathoracic pressure on cardiac performance during acute endotoxemia.

In the anesthetized closed-chest canine model of Gram-negative endotoxemia (n = 10), we tested the hypothesis that the effect of cardiac cycle-specific intrathoracic pressure pulses delivered by a heart rate-(HR) synchronized high-frequency jet ventilator (sync HFJV) on systolic ventricular performance is dependent on the level of preload. To control for HFJV frequency, hemodynamic responses were also measured at fixed frequency within 15% of HR (async HFJV). Biventricular stroke volumes (SV) were measured by electromagnetic flow probes. Measurements were made before (baseline) and 30 min after infusion of 1 mg/kg Escherichia coli endotoxin (serotype 055:B5) and then after 2 mg/kg propranolol at both low (less than 10 mmHg) left ventricular filling pressure (LVFP) and high (greater than 10 mmHg) LVFP. Ventricular function curves, aortic pressure-flow (P-Q) relationships, and venous return (VR) curves were analyzed. We found that endotoxin did not alter VR curves but shifted the aortic P-Q curves to the left with pressure on the x-axis (P less than 0.05). Volume loading increased SV (P less than 0.01) because of a rightward shift of the VR curve. No specific differences occurred with either sync or async HFJV during endotoxin, presumably because of preserved VR and shifted aortic P-Q. The lack of cardiac cycle-specific effects of ITP appears to be due to the selective endotoxin-induced changes in peripheral vasomotor tone that counterbalance any depressed myocardial contractility.

Myocardial clearance of Tc-99m hexakis-2-methoxy-2-methylpropyl isonitrile (MIBI) in patients with coronary artery disease.

Myocardial clearance of the new cationic, lypophilic myocardial perfusion agent, Tc-99m-hexakis-2-methoxy-2-methylpropyl isonitrile (MIBI) was studied in nine patients with coronary artery disease. Regional time-activity curves were determined from serial postexercise myocardial SPECT images after a single dose of Tc-99m MIBI. There were significant differences between the clearance rates from normal and ischemic myocardium. Tc-99m MIBI washout from normal myocardium was 27 +/- 8% by 6 hours after injection. Clearance from mild myocardial defects (initial activity greater than 60% of the activity in normal myocardium) was 16% by 6 hours in six patients. No washout was detected by 6 hours in the three patients with severe myocardial defects. The ratio between the activity in ischemic and normal myocardium increased from 0.70 +/- 0.08 to 0.80 +/- 0.13 and 0.84 +/- 0.13 at 4 and 6 hours after injection in the patients with mild defects. In the patients with large defects, the ratio increased from 0.42 +/- 0.09 to 0.54 +/- 0.07 at 6 hours. It is concluded that, while redistribution is substantially slower than with Tl-201, image interpretation and data evaluation should be approached cautiously when imaging is delayed 4 hours or more after injection of Tc-99m MIBI. Quantitative techniques aimed at evaluating the extent and intensity of myocardial ischemia will be particularly affected.

Comparison of technetium-99m sulfur colloid and technetium-99m albumin colloid labeled solid meals for gastric emptying studies.

A Tc-99m albumin colloid (Tc-AC) kit has been introduced as an alternative to Tc-99m sulfur colloid (Tc-SC) for liver-spleen imaging. Since there is no need for boiling, the use of Tc-AC reduces preparation time and manipulation. Tc-SC is one of the most commonly used radiopharmaceuticals for the labeling of solid-phase markers in gastric emptying studies. In vitro studies were performed to evaluate the labeling efficiency and stability in hydrochloric acid and in human gastric juice of intracellularly labeled chicken liver and scrambled eggs labeled with Tc-SC and Tc-AC. Gastric emptying studies also were performed on 20 healthy volunteers with both Tc-SC and Tc-AC labeled scrambled egg sandwiches. There was no significant difference between Tc-SC and Tc-AC in the labeling efficiency of chicken liver (98% +/- 1% for Tc-SC, 96% +/- 2% for Tc-AC) and scrambled eggs (92% +/- 2% for Tc-SC, 91% +/- 3% for Tc-AC). However, both Tc-SC and Tc-AC labeled scrambled eggs showed a lower stability than chicken liver, particularly in human gastric juice. Gastric emptying curves from both meals in 20 normal subjects were also similar, with a mean half-emptying time of 85 +/- 13 minutes and 87 +/- 16 minutes for the meals containing Tc-SC and Tc-AC respectively. Tc-AC is a reliable alternative to Tc-SC as a radiotracer for solid-phase gastric emptying studies.

Budd-Chiari syndrome: typical and atypical scintigraphic aspects.

Budd-Chiari syndrome, a well known entity, is often difficult to diagnose, mostly due to the nonspecificity of its symptomatology. Radiocolloid liver scans were evaluated in eight cases of this disease, proven by surgical biopsy. Five cases showed the "classic" scintigraphic pattern of caudate lobe hypertrophy (62.5%), and other abnormalities observed included segmental hepatic insufficiency, diffuse hepatic insufficiency, and relative hypertrophy of both the caudate lobe and a portion of the parenchyma of segment VI (one case each). An experimental study of hepatic venous drainage performed on livers at autopsy revealed four groups of accessory hepatic veins in addition to the main hepatic veins. The occlusion of various parts of this drainage appears to relate to the various scintigraphic patterns that were encountered in patients with Budd-Chiari syndrome. A review of the literature revealed three additional patterns previously reported in association with Budd-Chiari syndrome (normal scan, diffuse hepatomegaly, and multiple filling defects). If all these variations are appreciated, liver scanning can be a valuable screening tool for Budd-Chiari syndrome and may also serve as a noninvasive means of follow-up.

Augmentation of cardiac function in end-stage heart failure by combined use of dobutamine and amrinone.

A patient with end-stage congestive cardiomyopathy had progressive hemodynamic deterioration while awaiting orthotopic heart transplantation. Attempts to support cardiovascular function by high-dose dobutamine infusions were complicated by life-threatening cardiac arrhythmias. The addition of the noncatecholamine inotropic agent, amrinone, improved ventricular performance, enabling reduction of the dose of dobutamine and resolution of the cardiac arrhythmias. Beta receptor stimulation by dobutamine combined with phosphodiesterase inhibition by amrinone may additively or synergistically augment cardiac function despite severe congestive heart failure and also have an adrenergic "sparing effect."

Manual dexterity test in relation to obesity and hyperostosis frontalis interna in elderly women.

A manual dexterity test was performed in a population of elderly women. Obese subjects with hyperostosis frontalis interna (HFI) had a poorer performance than subjects with either HFI alone or obesity alone. The combined effects of cerebral arteriosclerosis and HFI is suggested as a possible explanation for these findings.