Classification-algorithm evaluation: five performance measures based on confusion matrices.

OBJECTIVE: The objective of this paper is to introduce, explain, and extend methods for comparing the performance of classification algorithms using error tallies obtained on properly sized, populated, and labeled data sets. METHODS: Two distinct contexts of classification are defined, involving "objects-by-inspection" and "objects-by-segmentation." In the former context, the total number of objects to be classified is unambiguously and self-evidently defined. In the latter, there is troublesome ambiguity. All five of the measures of performance here considered are based on confusion matrices, tables of counts revealing the extent of an algorithm's "confusion" regarding the true classifications. A proper measure of classification-algorithm performance must meet four requirements. A proper measure should obey six additional constraints. RESULTS: Four traditional measures of performance are critiqued in terms of the requirements and constraints. Each measure meets the requirements, but fails to obey at least one of the constraints. A nontraditional measure of algorithm performance, the normalized mutual information (NMI), is therefore introduced. Based on the NMI, methods for comparing algorithm performance using confusion matrices are devised. CONCLUSIONS: The five performance measures lead to similar inferences when comparing a trio of QRS-detection algorithms using a large data set. The modified NMI is preferred, however, because it obeys each of the constraints and is the most conservative measure of performance.

Inhibition of neutrophil adhesion does not prevent ischemic spinal cord injury.

Paraplegia may occur after transient aortic occlusion as a consequence of primary ischemia to the spinal cord or injury during the reperfusion period. In animal models of ischemia/reperfusion there is evidence that reperfusion injury may be modulated partially by neutrophils. The efficacy of the neutrophil adherence blocking murine monoclonal antibody (MAb 60.3) was assessed in spinal cord ischemia/reperfusion in rabbits. Spinal cord ischemia was accomplished by balloon catheter occlusion of the infrarenal aorta. Neurologic assessment was graded as normal, partial neurologic deficit, or complete paralysis. Electrophysiologic monitoring with somatosensory evoked potentials was used to determine the optimal length of time of occlusion. Animals were treated randomly with 2 mg/kg of intravenous Mab 60.3 (n = 8) or saline solution (n = 9) with the investigator unaware of treatment. Mean occlusion times were no different between groups (control, 32.7 +/- 3.6 minutes versus MAb, 32.4 +/- 6.0 minutes). Five (55%) saline-treated and four (50%) MAb 60.3-treated animals became paraplegic. Animals with initial paraparesis all progressed to flaccid paraplegia within 24 hours. We conclude that spinal cord injury after transient aortic occlusion is independent of the CD11/CD18 glycoprotein complex of the neutrophil. Injury in this setting may occur during ischemia and thus may not be dependent on neutrophils or reperfusion.

Mechanical circulatory support during repair of thoracic aortic injuries improves morbidity and prevents spinal cord injury.

OBJECTIVE: Evaluation of mechanical circulatory support (MCS) vs simple cross clamping (CC) during repair of traumatic descending thoracic aortic transections. DESIGN: A retrospective analysis of all patients admitted with blunt traumatic injury to the descending thoracic aorta from August 1988 through March 1993. Patients were pseudorandomized to simple CC vs MCS according to the on-call surgeons' preferences. SETTING: A level 1 trauma center in Seattle, Wash. PATIENTS: Forty-two patients were admitted. Thirty (71%) survived, 21 of whom underwent repair with MCS and nine underwent repair with CC only. INTERVENTION: Prompt aortic repair was performed either primary or by replacement with a Dacron graft. MAIN OUTCOME MEASURES: Operative survivors were examined for new neurologic deficits, renal function, pulmonary failure, gastrointestinal tract complications, sepsis, and length of hospitalization. Causes of death in all patients were determined. RESULTS: Twelve patients died, seven before surgery and five during surgery. In survivors, new neurologic deficits occurred in four (44%) of nine patients undergoing repair with CC and in none of the patients undergoing repair with MCS (P = .0005). Mean (+/- SEM) postoperative serum creatinine levels were higher in patients undergoing repair with CC (256 +/- 80 mumol/L [2.9 +/- 0.9 mg/dL]) than in patients undergoing repair with MCS (115 +/- 18 mumol/L [1.3 +/- 0.2 mg/dL]) (P < .05). Patients undergoing repair with CC had longer hospitalization and higher incidence of pulmonary, gastrointestinal, and septic complications, all of which approached statistical significance. CONCLUSIONS: Mechanical extracorporeal perfusion of the distal aorta during occlusion of the thoracic aorta for traumatic descending thoracic aortic injuries may prevent spinal cord ischemia and reduce postoperative organ dysfunction.

Schwannoma of the left atrium: diagnostic evaluation and surgical resection.

A case of primary benign schwannoma of the left atrium is reported. A 35-year-old man presented with new onset atrial fibrillation. Noninvasive evaluation revealed a 4 x 7-cm mediastinal mass either directly posterior to or involving the left atrium. The histologic diagnosis and specific location of the mass were established by incisional biopsy through a left thoracotomy. On cardiopulmonary bypass the tumor was resected by widely excising the posterior left atrium. The residual 20-cm2 left atrial defect was patched with pericardium. This unusual case illustrates that left atrial tumors originating near the pulmonary veins may be nonmyxomatous neoplasms of neural origin. Diagnosis may be difficult and require a surgical transthoracic approach.

Acquired immunodeficiency syndrome-related lymphoma of the lung presenting as empyema thoracis.

B-cell lymphoma in patients infected with the human immunodeficiency virus is usually a disseminated process that occasionally involves the lungs. Surgical diagnosis is often necessary to distinguish this from other neoplasms or opportunistic infections of the lung. We report a case of pulmonary B-cell lymphoma in a patient infected with human immunodeficiency virus who presented with a left empyema thoracis and an associated left lower lobe abscess secondary to bronchial obstruction. Resection was performed and the patient subsequently recovered from the acute process and survived an additional 6 months. This report demonstrates that surgical intervention may be necessary for both the diagnosis of pulmonary lymphoma and the definitive management of infectious complications that may arise as a result of pulmonary neoplastic disease in patients with acquired immunodeficiency syndrome.

Echocardiographic volume flow and stenosis severity measures with changing flow rate in aortic stenosis.

The anatomy of degenerative valvular aortic stenosis has been poorly represented in animal models, limiting the evaluation of noninvasive echo-Doppler measures of transvalvular volume flow rate and stenosis severity during progressive disease evolution or under conditions of changing volume flow rates. To study these issues, chronic valvular aortic stenosis, characterized by stiff leaflets without commissural fusion, was created in nine adult mongrel dogs by suturing pericardial covered Teflon-felt pads into the sinuses of Valsalva below the coronary ostia during hypothermic cardiac arrest. In the eight surviving dogs, echo-Doppler examinations were performed weekly for up to 8 wk postoperatively. Simultaneous invasive micromanometer pressure data were collected at 2-wk intervals in all subjects, with simultaneous ascending aortic transit time-volume flow measurement in four subjects. Volume flow rates were altered with saline and dobutamine infusions during invasive studies for comparison of echo-Doppler and invasive pressure gradients, volume flow, and valve areas. Serial echo-Doppler follow-up (39 +/- 11 days) demonstrated that, from baseline to final study, mean transvalvular pressure gradient increased (4 +/- 1 to 38 +/- 7 mmHg, P = 0.001), continuity equation aortic valve area decreased (2.06 +/- 0.18 to 0.54 +/- 0.04 cm2, P < 0.0001), and progressive left ventricular hypertrophy developed (62 +/- 6 to 114 +/- 9 g, P = 0.0003). Echo-Doppler and invasive data correlated well for measures of transvalvular pressure gradients (n = 98, maximum instantaneous gradient r = 0.95, mean gradient r = 0.91), volume flow (n = 75, stroke volume r = 0.86, cardiac output r = 0.86), and valve area (n = 73, r = 0.73) despite acute alterations in volume flow and progressive disease evolution. This chronic canine model, with anatomy and hemodynamics similar to clinical degenerative valvular aortic stenosis, should provide a valuable tool for investigating clinically relevant new measures of stenosis severity with use of invasive or noninvasive techniques.

A QRS detection algorithm.

In this article we present the choices that the designers of any QRS detector must make and explain the constraints we adopted. We outline the signal processing that precedes and the beat analysis that follows QRS detection in our single-channel, arrhythmia-monitoring algorithm and then expound the QRS detection algorithm in detail. Finally, we present the results of a QRS detector performance evaluation and comment on their importance. This article can be read to three depths: the text affords an overview of QRS detection for on-patient, ambulatory arrhythmia analysis; the commented pseudocode documents the logic of our QRS detector; and the pseudocode "footnotes" supply technical detail.

Strategies in the design of solution-stable, water-soluble prodrugs III: influence of the pro-moiety on the bioconversion of 21-esters of corticosteroids.

Succinate esters and many other carboxylic acid esters utilized as water-soluble prodrugs have limited utility due to their aqueous solution instability. In an earlier study, a strategy for the design of solution-stable 21-carboxylic acid esters of corticosteroids was developed from a consideration of various physical organic factors which influence ester hydrolysis. Several 21-esters of methylprednisolone were synthesized, and their stability in aqueous solution was monitored to demonstrate the feasibility of the approach. In this study, the bioconversion of representative examples of 21-esters of methylprednisolone exhibiting shelf lives of greater than or equal to 2 years at 25 degrees C was monitored to evaluate their utility as prodrugs in comparison to a commercially marketed sodium succinate ester. Ester hydrolysis studies conducted in human and rhesus monkey serum suggest that derivatives having an anionic solubilizing moiety (sulfonate or carboxylate) are not hydrolyzed in serum, while compounds having a cationic (tertiary amino) solubilizing moiety are hydrolyzed rapidly by serum esterases. In vivo pharmacokinetic studies in rhesus monkeys were also conducted to compare the bioconversion rates and overall bioavailability of several solution-stable prodrugs with the 21-succinate ester. Derivatives having solution stability exceeding 2 years at 25 degrees C with a faster bioconversion rate and an overall bioavailability equal to or higher than that of the succinate ester have been identified. Relative bioavailability appears to be highly sensitive to the charge of the solubilizing pro-moiety and pro-moiety chain length.

Menses induction in rhesus monkeys using a controlled-release vaginal delivery system containing (15S) 15-methyl prostaglandin F2 alpha methyl ester.

Polymeric controlled-release vaginal delivery systems were designed for (15S)15-methyl prostaglandin (PG)F2 alpha methyl ester (carboprost methyl). The drug was incorporated into a highly permeable reservoir membrane that was bound to a relatively nonpermeable support membrane. The rate of drug release was controlled by coating the reservoir membrane with a less permeable rate-controlling membrane. Vaginal devices were prepared with in vitro steady-state release rates from 5 to 180 microgram/hour. The release curves were characterized by an initial, transient rapid release of the drug, followed by a linear zero-order release phase. Pregnancy was terminated in rhesus monkeys following a 24-hour treatment with vaginal devices having release rates of carboprost methyl of 45 microgram/hour or greater. Successful menses induction was associated with peripheral plasma concentrations of (15S)15-methyl PGF2 alpha between 2000 and 3000 pg/ml. Peripheral plasma concentrations of progesterone declined very rapidly to less than 1.0 ng/ml in monkeys in which pregnancy was terminated. These studies demonstrate the feasibility of manufacturing controlled-release vaginal delivery systems containing carboprost methyl for use in early pregnancy termination.

Contraceptive efficacy of testosterone-estradiol implants in male rhesus monkeys.

Rhesus monkeys (Macaca mulatta) were treated with testosterone (100 micrograms/kg/day) plus estradiol (0.5 micrograms/kg/day) via subcutaneous polydimethylsiloxane (PDS, Silastic) implants. This treatment caused a striking reversible sterility. No pregnancies were observed in females bred to the steroid-treated males. In contrast, there was no difference in pregnancy rate of females bred to control and steroid-treated monkeys for 14 weeks, beginning 17 weeks after removal of the steroid-filled implants.

Serum FSH, LH and testosterone in the male rhesus following prostaglandin injection.

Adult male rhesus were treated with PGE2, PGF2 alpha or the 13,14-dihydro-15-keto metabolite of PGE2 in a randomized crossover design. Serum concentrations of FSH, LH and testosterone were determined and compared to the respective values in the same uninjected animals. No significant changes were noted in controls or following the metabolite injection. FSH increased gradually for 4 hours after metabolite treatment. In contrast, injection of PGF2 alpha was followed by an abrupt (within 15 minutes) increase in LH and testosterone. FSH increased gradually in 2 of 3 treated animals. Injection of PGE2 was followed by a similar abrupt increase in LH concentration. This was not always associated with a significant increase in testosterone or FSH. These results demonstrate that injections of PGE2 or PGF2 alpha can change serum gonadotropin and testosterone concentrations in male rhesus monkeys, and that the effects of these two prostaglandins are qualitatively different.

Characterization of the exfoliative antispermatogenic agent 1-(2,4-dichlorobenzyl)-H-indazole-3-carboxylic acid in the rhesus monkey.

The effects of oral doses of 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid (DICA) on spermatogenesis in the rhesus monkey (Macaca mulatta) was studied. Four animals given five daily 50 mg/kg doses or three or five daily 500 mg/kg doses showed that DICA was an exfoliating antispermatogenic compound. The inhibition of spermatogenesis was only partially reversible following 500 mg/kg doses of DICA. Weekly and monthly 50 mg/kg doses of DICA only partially inhibiting spermatogenesis as measured by electro-ejaculated sperm counts. Response in individual monkeys ranged from azoospermia to no effect. Testicular biopsies confirmed this finding. DICA did not affect serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), or testosterone concentrations. The blood absorption or urinary excretion rates of uniformly tritiated DICA in the animals that responded well did not differ from those monkeys that responded poorly. DICA metabolites were not detected in monkey urine. Serum testosterone concentrations appeared to vary with the season of the year, but FSH concentrations and ejaculated sperm count did not.

Effects of PGF2alpha and PGF2alpha, 1-15 lactone on the corpus luteum and on early pregnancy in the rhesus monkey.

The effects of prostaglandin (PG)F2alpha and PGF2alpha, 1-15 lactone were compared in luteal phase, non-pregnant and in early pregnant rhesus monkeys. Animals treated with either PG after pretreatment with human chorionic gonadotropin (hCG) had peripheral plasma progesterone concentrations that were not statistically different from those in animals treated with hCG and vehicle. However, menstrual cycle lengths in monkeys treated with PGF2alpha, 1-15 lactone were significantly (P less than 0.02) shorter than those in vehicle treated animals. In the absence of hCG pretreatment, plasma progesterone concentrations were significantly (P less than 0.008) lower by the second day after the initial treatment with either PGF2alpha or PGF2alpha, 1-15 lactone than in vehicle treated monkeys. Menstrual cycle lengths in monkeys treated with either PG were significantly (P less than 0.04) shorter than those in animals treated with vehicle. There were no changes in plasma progesterone concentrations in early pregnant monkeys treated with PGF2alpha, and pregnancy was not interrupted. In contrast, plasma progesterone declined and pregnancy was terminated in 5 of 6 early pregnant monkeys treated with PGF2alpha, 1-15 lactone. These data indicate that PGF2alpha, 1-15 lactone decreases menstrual cycle lengths in non-pregnant rhesus monkeys. More importantly, PGF2alpha, 1-15 lactone terminates early pregnancy in the monkey at a dose which is less than an ineffective dose of PGF2alpha.

Effects of 19-hydroxy-prostaglandins on oviductal and uterine motility.

The effects of 19-hydroxyprostaglandins (19-OH-PGs) were tested in vivo on the rabbit oviduct and uterus and on the rhesus monkey (Macaca mulatta) uterus. The 19-OH-PGEs suppressed spontaneous oviductal and uterine activity in the rabbit. The qualitative effect on the rabbit oviduct of 19-OH-PGEs was similar to that of PGE2. However, the typical response of the rabbit uterus to PGE2 was an increase in muscle activity. With regard to the rabbit oviduct, 19(R)-OH-PGE2 was as potent as PGE2, but 19(S)-OH-PGE2 was approximately 1/2 as potent as PGE2. Based on the dose of 19-OH-PGEs usually required to cause a minimal suppression and the dose of PGE2 required to cause a minimal stimulation of rabbit uterine activity, 19(R)-OH-PGE2 was twice as potent as PGE2 while 19(S)-OH-PGE2 was 1/2 as potent as PGE2. Stimulatory effects on the rabbit oviduct and uterus were observed following administration of 19-OH-PGFs and PGF2alpha. The potency on the rabbit oviduct of 19(S)-OH-PGF2alpha was about 1/5 to 1/10 that of PGF2alpha; the potency of 19(R)-OH-PGF2alpha was about 1/10 to 1/20 that of PGF2alpha. Both 19-OH-PGFs were approximately 1/5 to 1/10 as potent as PGF2alpha on the rabbit uterus. At the doses tested 19-OH-PGFs were inactive on the monkey uterus. Thus, these compounds are at least 1/5 as active as PGF2alpha. In contrast, 19(R)-OH-PGE2 had approximately the same potency as PGE2 in stimulating monkey uterine activity; but 19(S)-OH-PGE2 was approximately 1/3 as potent as PGE2.

Evaluation of vaginal delivery systems containing 15[s]15-methyl PGF2alpha methyl ester.

Silicone vaginal delivery systems containing 15[S]15-methyl-PGF2alpha methyl ester have been evaluated in vitro, and in vivo in the rhesus monkey. Three types of vaginal devices have been formulated to contain different concentrations of drug. The cumulative amount of 15[s]15-methyl-PGF2alpha methyl ester released in vitro from a planar silicone rubber matrix was dependent upon the initial loading dose of the prostaglandin. Drug-containing vaginal rings were evaluated in early pregnant and mid-trimester pregnant monkeys. Within 10 min after ring administration there was an increase in the amplitude and frequency of contractions. In mid-trimester pregnant animals there was an initial increase in plasma progesterone and then a decrease following treatment, while there was a progressive decrease in plasma progesterone in early pregnant animals. All 6 mid-trimester pregnant monkeys treated with vaginal rings aborted. Pregnancy was terminated in 4 of 5 early pregnant monkeys treated with vaginal rings. Blood levels of 15-methyl-PGF2alpha rose rapidly to attain a peak 1 hr after treatment with vaginal rings. After the peak, plasma levels of 15-methul-PGF2alpha declined to a plateau which was fairly constant between 2 and 8 hr. Vaginal silicone-gelatin laminates containing 15[s]15-methyl-PGF2alpha methyl ester were also effective in causing an increase in uterine muscle activity and terminating pregnancy in mid-trimester in pregnant monkeys. Plasma progesterone also increased shortly after treatment in these animals, and then declined after the peak at 8 hr. The plasma profile of 15-methyl-PGF2alpha when animals were treated with these vaginal laminates was different from that observed following ring treatment. In pregnant animals the concentration of 15-methyl-PGF2alpha rose more slowly following laminate insertion, and the peak values were considerably less than those following ring treatment. Vaginal devices used in monkeys and humans caused plasma concentrations of 15-methyl-PGF2alpha that were generally lower than those observed in monkeys treated with either vaginal rings or laminates. These studies have demonstrated that silicone vaginal delivery systems containing 15[S]15-methyl-PGF2alpha methyl ester result in sustained and fairly constant plasma levels of 15-methyl-PGF2alpha, and terminate both 1st- and 2nd-trimester pregnancies in the monkey. The vaginal device offers the possibility for self-administration of PGs for early pregnancy termination and menstrual cycle regulation.

Sound envelope averaging and the differential diagnosis of systolic murmurs.

Phonocardiography previously has been limited in scope because the attained suboptimal signal-to-noise ratio has interfered with the sensitivity and clarity of recordings. A new system is described that reduces this problem by utilizing demodulation and synchronous averaging of the "envelop" of cardiac sounds. A limited survey of the differential diagnostic capabilities of this technique is presented for 80 patients having one of six common forms of pathological systolic murmurs and an 89 per cent diagnostic accuracy is demonstrated. This system promises to be a valuable noninvasive adjunct in cardiologic diagnosis research and education.