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Objective: To assess whether mifepristone pretreatment adversely affects the cost of medical management of miscarriage., Methods: Decision tree analyses were constructed, and Monte Carlo simulations were run comparing costs of combination therapy (mifepristone and misoprostol) with monotherapy (misoprostol alone) for medical management of miscarriage in multiple scenarios weighing clinical practice, patient income, and surgical evacuation modalities for failed medical management. Rates of completed medical evacuation for each were obtained from a recent randomized controlled trial., Results: In every scenario, combination therapy offered a significant cost advantage over monotherapy. Using a Monte Carlo analysis, cost differences favoring combination therapy ranged from 6.3% to 19.5% in patients making federal minimum wage. The cost savings associated with combination therapy were greatest in scenarios using a staged approach to misoprostol administration and in scenarios using in-operating room dilation and curettage as the only modality for uterine evacuation, a savings of $190.20 (99% CI 189.35-191.07) and $217.85 (99% CI 217.19-218.50) per patient in a low-income wage group, respectively. A smaller difference was seen in scenarios using in-office manual vacuum aspiration to complete medical management failures. As patients' wages increased, the difference in cost between combination therapy and monotherapy increased., Conclusion: Mifepristone combined with misoprostol is, overall, more cost effective than monotherapy, and therefore cost should not be a deterrent to its adoption in the management of miscarriage.

Background: The AFFIRM Study showed that treatment of patients with atrial fibrillation and a high risk for stroke or death with a rhythm-control strategy offered no survival advantage over a rate-control strategy in an intention-to-treat analysis. This article reports an "on-treatment" analysis of the relationship of survival to cardiac rhythm and treatment as they changed over time., Methods and Results: Modeling techniques were used to determine the relationships among survival, baseline clinical variables, and time-dependent variables. The following baseline variables were significantly associated with an increased risk of death: increasing age, coronary artery disease, congestive heart failure, diabetes, stroke or transient ischemic attack, smoking, left ventricular dysfunction, and mitral regurgitation. Among the time-dependent variables, the presence of sinus rhythm (SR) was associated with a lower risk of death, as was warfarin use. Antiarrhythmic drugs (AADs) were associated with increased mortality only after adjustment for the presence of SR. Consistent with the original intention-to-treat analysis, AADs were no longer associated with mortality when SR was removed from the model., Conclusions: Warfarin use improves survival. SR is either an important determinant of survival or a marker for other factors associated with survival that were not recorded, determined, or included in the survival model. Currently available AADs are not associated with improved survival, which suggests that any beneficial antiarrhythmic effects of AADs are offset by their adverse effects. If an effective method for maintaining SR with fewer adverse effects were available, it might be beneficial.

Preterm infant formulas (PIFs) for very-low-birth-weight (VLBW) infants (birth weight, < 1,500 g) are augmented to provide daily riboflavin and pyridoxine at levels up to five-fold greater than in term infant formula and 18-fold greater than in human milk. We evaluated plasma riboflavin and pyridoxine concentrations in VLBW infants who received PIF during their first postnatal month. Eighty-eight plasma and 124 urine samples were collected for riboflavin- and pyridoxine-concentration measurements from 57 clinically healthy VLBW infants weekly during their first postnatal month. Concentrations were measured using high-performance liquid chromatography. At the time of the sample, patients were receiving > or = 80% of their total calories via enteral feedings. Plasma riboflavin concentrations rose from 45.3 +/- 7.3 ng/ml at baseline (mean +/- SEM) to 173.5 +/- 20.3 ng/ml by 1 week of age and remained at 177.3-199.7 ng/ml during the following three weekly measurements; values were up to 14-fold above baseline concentration. Urine riboflavin concentration increased from 534 +/- 137 ng/ml at baseline to 3,521 +/- 423 ng/ml by 1 week of age and remained at 4,451-5,216 ng/ml during the next 3 weeks. In a similar pattern, baseline plasma (69.4 +/- 10.4 ng/ml) and urine (145 +/- 30 ng/ml) pyridoxine concentrations were significantly increased by 1 week postnatal age; they remained at 163-248 ng/ml (plasma) and 1,573-2,394 ng/ml (urine) through the first postnatal month. Plasma and urine riboflavin and pyridoxine concentrations in enterally fed VLBW infants increased from baseline concentrations by 1 week of postnatal age and remained elevated for the first postnatal month. High daily intake and immature renal development are probable contributing causes of the elevated plasma riboflavin and pyridoxine concentrations. We suggest that lower daily enteral administration of riboflavin and pyridoxine should maintain adequate blood concentrations and minimize potential toxicity.

A consistently effective transvenous defibrillation system for use in automatic defibrillators could significantly alter the approach to patients at risk of sudden death. Transvenous defibrillation systems that use a right ventricular (RV) electrode only or an RV electrode in combination with a chest patch are relatively inefficient at applying current to the posterolateral left ventricle. An RV electrode combined with a coronary sinus (CS) electrode, however, may improve current distribution to the posterolateral left ventricle. The purpose of this investigation, therefore, was to evaluate the effectiveness and safety of a specially designed transvenous lead system with a CS electrode capable of current delivery to this relatively inaccessible region of the heart. In 20 survivors of cardiac arrest, we determined defibrillation efficacy immediately before defibrillator surgery for monophasic pulses delivered between an RV catheter electrode and a CS catheter electrode system and compared these findings with an RV catheter electrode-thoracic patch defibrillation system. Subsequently, we referenced the efficacy of both transvenous systems to an epicardial patch electrode system at the time of defibrillator implantation. The mean delivered-energy defibrillation threshold for the CS-RV electrode system was 17.5 +/- 7.9 J, which was substantially lower than the RV electrode-thoracic patch system (25.6 +/- 11.4 J, p = 0.0016 [46% more]). Defibrillation threshold voltage was 529 +/- 123 V for the CS-RV electrode system and 647 +/- 164 V (22% more) for the RV electrode-thoracic patch system (p = 0.0013).(ABSTRACT TRUNCATED AT 250 WORDS)

Voltage waveform breakdown is characteristic of barotraumatic shock-wave generation during electrical catheter ablation of cardiac arrhythmias. The purpose of this investigation was to avoid barotrauma by defining, in vitro, the limits of pulse amplitude and pulse width for rectangular constant-current pulses that do not result in voltage breakdown and subsequently to determine what pulsing frequency is safe for use when high-energy trains of pulses are used. Electric pulses were delivered with a variable waveform modulator with a wide dynamic range and bandwidth capable of delivering pulses of 30-10,000-mu sec duration with amplitudes of up to 25 A. Cathodal pulses were delivered to a 6F catheter immersed in fresh anticoagulated bovine blood warmed to 37 degrees C to stimulate the milieu of a catheter in the chambers of the human heart. The maximum pulse amplitude that could be delivered without incurring voltage waveform breakdown varied inversely with pulse duration. Pulses of 30 mu sec broke down at currents above 24 A (2,500 V). Pulses of 10,000-mu sec duration broke down at 1 A (250 V). The maximum safely delivered energy for a single pulse was 2.5 J for pulses of 80-120 mu sec. Peak power for single pulses was maximum at 50-55 kW with 30-50-mu sec pulses. Charge delivery for single pulses was maximized at 9 mC with long, 10,000-mu sec duration pulses. To deliver an electrical pulse with energy significantly greater than 2.5 J without incurring voltage breakdown, trains of pulses were delivered where each pulse in the train had previously been shown to be free of voltage breakdown.(ABSTRACT TRUNCATED AT 250 WORDS)

We compared two methods of delivering single damped sine-wave defibrillator pulses to the coronary sinus orifice in 20 dogs. Ten dogs had "unipolar" (coronary sinus to precordial disc) and 10 had "bipolar" (coronary sinus proximal to coronary sinus distal electrode) discharges. Delivered voltage, current, and energy were recorded during each pulse. Electrophysiologic testing was done before and 4 weeks after the procedure. Histologic examination of the atrioventricular groove was done at 1 mm serial sections. For the unipolar configuration a 200 J defibrillator pulse resulted in a peak voltage of 3370 +/- 125 V, a peak current of 21 +/- 4 A, and a delivered energy of 253 +/- 29 J as compared with 3010 +/- 99 V, 70 +/- 4 A, and 144 +/- 18 J, respectively, for the bipolar configuration (p less than .001). Three dogs (two with bipolar, one with unipolar pulses) had gross coronary sinus rupture and died from acute pericardial tamponade. In addition, irrespective of electrode configuration, all dogs showed microscopic rupture of the coronary sinus internal elastic membrane. Transmural atrial scarring occurred in all 10 dogs that received a unipolar pulse but in only two dogs that received a bipolar pulse (p = .0004). Unlike the atrium, injury to the left ventricle was limited in both groups. Similarly, injury to the periannular myocardium was inconsistent and not transmural in either group. No significant electrophysiologic changes were observed. With the present technique, unipolar rather than bipolar catheter-mediated defibrillator pulses result in transmural atrial injury that might prevent accessory pathway conduction. Regardless of electrode configuration, high-energy defibrillator pulses consistently cause some degree of coronary sinus rupture, most likely related to a barotraumatic mechanism.

Five patients who underwent cardiopulmonary resuscitation (CPR) were studied by two-dimensional echocardiography to assess valve motion. The mitral valve remained open throughout the entire compression-release cycle of CPR. The aortic valve opened during the compression phase of CPR and closed during the release phase. The pulmonic valve moved toward the closed position during the compression phase and the valve leaflets opened during release. Tricuspid valve leaflets never completely apposed, even during maximum chest compression, and they were widely open during release. Left ventricular dimensions did not change appreciably during CPR. These findings support the theory that forward blood flow during CPR depends on a generalized increase in intrathoracic pressure and not on direct compression of the heart itself. The left heart appears to act as a conduit for passage of blood, and mitral valve closure is not necessary for forward blood flow during CPR.

Glutathione peroxidase is an important enzyme in the degradative cascade of reactive oxygen free radicals. N-Acetylcysteine (NAC) is a low molecular weight compound that has been used clinically to replenish glutathione. To assess the role of the glutathione redox pathway on reperfusion injury, 23 animals underwent 90 minutes of proximal left anterior descending coronary artery occlusion followed by 24 hours of reperfusion with the administration of NAC (n = 11) or saline (n = 12) beginning 30 minutes into occlusion and continuing for 3 hours after reperfusion. Regional ventricular function was measured with contrast ventriculography, and regional myocardial blood flow was determined with microspheres. At 24 hours, the area at risk was defined in vivo with Monastral Blue, and the area of necrosis was defined by incubation in triphenyltetrazolium. Biopsies were taken from the ischemic and nonischemic zones to determine levels of total glutathione, superoxide dismutase and glutathione peroxidase activity, and reactivity to thiobarbituric acid, an index of lipid peroxidation. The rate-pressure product and myocardial blood flow were similar in the two groups throughout the study. No significant differences were noted in infarct size expressed as a percentage of the area at risk (28.6 +/- 5.3% vs. 36.6 +/- 6.0%) and of the total left ventricle (14.4 +/- 3.2% vs. 16.5 +/- 3.1%), and no differences were noted between the two groups on examination of the ischemic subendocardium by light and electron microscopy. Both groups exhibited similar degrees of dyskinesis during occlusion; however, treated animals showed significant improvement in regional radial shortening at 3 hours (3.4 +/- 2.4% vs. -2.4 +/- 2.1%, p less than 0.02) and 24 hours (9.2 +/- 2.2% vs. -2.5 +/- 6.3%, p less than 0.001) after reperfusion. No differences were present in total glutathione, thiobarbituric acid reactivity, or superoxide dismutase and glutathione peroxidase activity in the ischemic zones of the two groups. This study suggests that N-acetylcysteine treatment before reperfusion may reduce myocardial stunning but does not limit myocyte death after reperfusion.

This report describes a 52-year-old black male with the isolated finding of an anomalous superior vena cava draining into the left atrium. The patient presented with dizziness, mild cyanosis, polycythemia and normal cardiac and pulmonary findings. The first major diagnostic clue in this confusing clinical presentation was an unsuccessful lung perfusion scan in which intravenous tracer consistently bypassed the lungs. This appears to be the first adult presenting with this rare anomaly. This condition should be suspected if cyanosis, clubbing, and a "normal" cardiac examination coexist and if the more common pulmonary and hematological causes of this triad have been excluded.

Factors affecting bubble formation during delivery of defibrillator pulses to arrhythmogenic cardiac tissue via a catheter are unknown. We investigated the role of energy, electrode surface area, interelectrode distance, and electrode polarity on bubble formation and on current and voltage waveforms during delivery of damped sinusoidal discharges from a standard defibrillator to anticoagulated bovine blood. Gas composition was studied with mass spectrometry. Defibrillator energy settings were varied between 5 and 360 J. The principal catheter used for study was a Medtronic 6992A lead. Additional electrodes tested included 2, 5, and 10 mm long No. 6F, 7F, and 8F copper electrodes. Interelectrode distances used to assess the effect of anode-cathode spacing were 1, 5, 10, and 20 cm. Bubble volume increased linearly from 0.043 to 0.134 ml per cathodal pulse and from 0.030 to 3.50 ml per anodal pulse as energy settings were increased from 5 to 360 J (r = .99). Typical smooth waveforms for both current and voltage were seen only in the absence of bubbles. The voltage waveform was distorted for each cathodal pulse of 100 J or more and for each anodal pulse of 10 J or more only if bubbles were present. The effect of electrode surface area on bubble formation was tested at a 200 J energy setting and at a 10 cm interelectrode distance with the use of cathodal pulses. Bubble formation varied inversely with electrode surface area (r = .876). Bubble formation, however, varied minimally as interelectrode spacing was changed from 1 to 20 cm. The effect of polarity on bubble formation when the Medtronic 6992A distal electrode and an 8.5 cm disk electrode separated by 10 cm were used was highly significant. For a 200 J pulse, bubble formation with the catheter as anode was 3.30 +/- 0.10 ml and with the catheter as cathode it was 0.070 +/- 0.002 ml (p less than .001). Mass spectrometry of both anodal and cathodal gas samples demonstrated the constituents of the gas bubble to include a variety of gases, which is inconsistent with simple electrolytic production of the bubbles observed. The predominance of nitrogen in either polarity sample suggested that the principal source of the bubble was dissolved air. In summary, bubble formation at an electrode receiving damped sinusoidal outputs from a standard defibrillator does not vary significantly with varying interelectrode distance. However, it is directly proportional to energy and inversely proportional to electrode surface area. Anodal catheter discharges produce considerably more bubbles than do cathodal discharges.(ABSTRACT TRUNCATED AT 400 WORDS)

A patient with glycogen storage disease type IB (GSD-Ib) is described. Beginning at age 34 months, the patient was managed with dietary measures, including nocturnal intragastric feedings. Therapy caused substantial biochemical and clinical improvement while the patient remained hospitalized; chronic noncompliance at home, however, resulted in profound growth failure and biochemical abnormalities. Due to a previous case report describing clinical, biochemical, and hematological improvement following a portacaval shunt in a similar patient, portacaval shunt was performed in our patient at age 13 years. During the 12 months following surgery, there was no improvement of our patient's growth or of biochemical or hematological abnormalities. Due to the lack of improvement following surgery, 24-hour constant infusion intragastric feedings were instituted and have been associated with substantial benefit.

In a series of 12 dogs, the electrophysiologic and histologic effects of a single damped sine-wave shock delivered via standard electrocatheters to the region of the coronary sinus orifice were investigated. Six dogs received 200 J and six received 360 J of stored energy. The shock was delivered to two consecutive proximal poles of a standard quadripolar catheter positioned at the coronary sinus orifice and connected to the positive output (anode) of a defibrillator. A disc electrode positioned on the anterior chest wall served as the cathode (negative pole). During the shock, voltage and current were recorded. Electrophysiologic testing was done before and 4 weeks after the shock. At 4 weeks, animals were killed and serial sections of the atrioventricular groove and conduction system were performed. No significant long-term change in atrioventricular conduction, spontaneous or induced atrial or ventricular arrhythmias was observed. However, transient atrioventricular block was seen in five and idioventricular rhythms in six animals in the short term. No persistent electrocardiographic changes were observed, and no sudden deaths occurred. Microscopically, transmural injury at the anulus proper or basilar ventricular epicardium was inconstant and infrequent. However, transmural atrial injury at the level of the coronary sinus was produced over a 10 +/- 5 mm length with the 200 J shock and a 21 +/- 6 mm length with the 360 J shock. Neither coronary artery injury nor damage to the conduction system was seen and cardiac tamponade did not occur. However, localized intramural atrial rupture of the coronary sinus wall (on the endocardial aspect only) was observed in each dog, consistent with barotrauma. With the present technique, atrial injury potentially capable of blocking the effects of accessory pathway conduction could be produced without other electrophysiologic alterations or complications. Injury to the anulus proper (and therefore to any accessory pathway per se) is probably unlikely. Barotrauma may play a significant role in the type of injury observed in this study.

Although gallbladder hydrops occurs frequently in patients with mucocutaneous lymph node syndrome (MCLS), the etiology of the gallbladder lesion is unclear. Recently we performed a liver biopsy on a child with severe MCLS and demonstrated selective invasion of biliary ductular epithelial cells by polymorphonuclear leukocytes with sparing of the hepatocytes. The possible role of the selective destruction of biliary cells in the pathogenesis of biliary disease in MCLS is discussed.

We prospectively studied 196 consecutive survivors of out-of-hospital ventricular fibrillation (VF) not associated with acute myocardial infarction and 46 consecutive, control patients without prior ventricular arrhythmias. Programmed stimulation included two extrastimuli (S3 protocol) in all patients and three extrastimuli (S4 protocol) in the last 140 study patients and in all control patients. Sustained ventricular tachycardia (VT) or VF was not induced in any control patient. In study patients, logistic regression identified two independent predictors of induced, sustained VT for both S3 and S4 protocols: prior spontaneous, sustained VT (37 patients; p less than or equal to .001) and prior myocardial infarction (113 patients; p = .005). With the S3 protocol, sustained VT was induced in 54% of patients with both prior myocardial infarction and prior sustained VT vs 4% without either; with the S4 protocol, sustained VT was induced in 91% vs 13%, respectively. Eighty-three percent of induced VT episodes had a cycle length less than 300 msec, and all required termination by cardioversion or pacing. VF was induced only in survivors of out-of-hospital VF without prior, spontaneous, sustained VT (S3 protocol, 9%; S4 protocol, 24%) but not in study patients with prior sustained VT (S3, p = .10; S4, p = .05) or control patients (S3, p = .06; S4, p = .01). The mean coupling intervals of extrastimuli that induced VF were not significantly different from the intervals that induced sustained VT.(ABSTRACT TRUNCATED AT 250 WORDS)

The number of preterm infants fed their own mother's milk appears to be increasing as a result of information suggesting certain benefits over milk from human milk banks or proprietary formulas. It is also apparent that the nutritional requirements of term and preterm infants differ. Thus, the finding of various deficiencies in small preterm infants indicates that studies which examine the nutrient content of milk from mothers who deliver prematurely are important to aid in suggesting appropriate supplementation. In order to provide appropriate recommendations, nutrient content must be assayed during the period of exclusive milk feedings. Accordingly, the concentrations and total daily output of breast milk zinc and copper, and vitamins A, C, and E, were examined in a group of 13 mothers delivering at or before 32 weeks gestation. Collections of a total 24-h output were obtained every 7 days for the first 7 weeks after delivery. Concentrations of all micronutrients were similar to those reported previously during the first 5 weeks of lactation. Most striking, however, was the progressive decline in total output as well as concentration of zinc. After the first 2 weeks of lactation, levels of copper and vitamins A, C, and E were not affected by the duration of lactation. There was substantial variation between mothers in daily output of all the micronutrients. The low output of these micronutrients suggests that some attempt should be made at monitoring the mineral and vitamin status of small preterm infants fed exclusively human milk for the first 3 months of life.(ABSTRACT TRUNCATED AT 250 WORDS)

A child with type III glycogen storage disease is described. The patient presented with growth failure and hepatic dysfunction, and no clinical or biochemical evidence of myopathy. Institution of high protein nocturnal intragastric feedings was associated with improved growth and less hepatic dysfunction. Compliance with tube feedings was sporadic necessitating another approach to the patient's management. The use of oral cornstarch supplements enabled the child to maintain normoglycemia and was associated with clinical and biochemical improvement. Our experience with this child suggests cornstarch therapy may be useful in those patients with type III glycogen storage disease who suffer primarily from hepatic dysfunction and growth failure.