Medicine in motion: Opportunities, challenges and data analytics-based solutions for traditional medicine integration into western medical practice.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional pharmacopeias have been developed by multiple cultures and evaluated for efficacy and safety through both historical/empirical iteration and more recently through controlled studies using Western scientific paradigms and an increasing emphasis on data science methodologies for network pharmacology. Traditional medicines represent likely sources of relatively inexpensive drugs for symptomatic management as well as potential libraries of new therapeutic approaches. Leveraging this potential requires hard evidence for efficacy that separates science from pseudoscience. MATERIALS AND METHODS: We performed a review of non-Western medical systems and developed case studies that illustrate the epistemological and practical translative barriers that hamper their transition to integration with Western approaches. We developed a new data analytics approach, in silico convergence analysis, to deconvolve modes of action, and potentially predict desirable components of TM-derived formulations based on computational consensus analysis across cultures and medical systems. RESULTS: Abstraction, simplification and altered dose and delivery modalities were identified as factors that influence actual and perceived efficacy once a medicine is moved from a non-Western to Western setting. Case studies on these factors highlighted issues with translation between non-Western and Western epistemologies, including those where epistemological and medicinal systems drive markets that can be epicenters for zoonoses such as the novel Coronavirus. The proposed novel data science approach demonstrated the ability to identify and predict desirable medicinal components for a test indication, pain. CONCLUSIONS: Relegation of traditional therapies to the relatively unregulated nutraceutical industry may lead healthcare providers and patients to underestimate the therapeutic potential of these medicines. We suggest three areas of emphasis for this field: First, vertical integration and embedding of traditional medicines into healthcare systems would subject them to appropriate regulation and evidence-based practice, as viable integrative implementation mode. Second, we offer a new Bradford-Hill-like framework for setting research priorities and evaluating efficacy, with the goal of rescuing potentially valuable therapies from the nutraceutical market and discrediting those that are pseudoscience. Third, data analytics pipelines offer new capacity to generate new types of TMS-inspired medicines that are rationally-designed based on integrated knowledge across cultures, and also provide an evaluative framework against which to test claims of fidelity and efficacy to TMS made for nutraceuticals.

Myrcene and terpene regulation of TRPV1.

Nociceptive Transient Receptor Potential channels such as TRPV1 are targets for treating pain. Both antagonism and agonism of TRP channels can promote analgesia, through inactivation and chronic desensitization. Since plant-derived mixtures of cannabinoids and the Cannabis component myrcene have been suggested as pain therapeutics, we screened terpenes found in Cannabis for activity at TRPV1. We used inducible expression of TRPV1 to examine TRPV1-dependency of terpene-induced calcium flux responses. Terpenes contribute differentially to calcium fluxes via TRPV1 induced by Cannabis-mimetic cannabinoid/terpenoid mixtures. Myrcene dominates the TRPV1-mediated calcium responses seen with terpenoid mixtures. Myrcene-induced calcium influx is inhibited by the TRPV1 inhibitor capsazepine and Myrcene elicits TRPV1 currents in the whole-cell patch-clamp configuration. TRPV1 currents are highly sensitive to internal calcium. When Myrcene currents are evoked, they are distinct from capsaicin responses on the basis of Imax and their lack of shift to a pore-dilated state. Myrcene pre-application and residency at TRPV1 appears to negatively impact subsequent responses to TRPV1 ligands such as Cannabidiol, indicating allosteric modulation and possible competition by Myrcene. Molecular docking studies suggest a non-covalent interaction site for Myrcene in TRPV1 and identifies key residues that form partially overlapping Myrcene and Cannabidiol binding sites. We identify several non-Cannabis plant-derived sources of Myrcene and other compounds targeting nociceptive TRPs using a data mining approach focused on analgesics suggested by non-Western Traditional Medical Systems. These data establish TRPV1 as a target of Myrcene and suggest the therapeutic potential of analgesic formulations containing Myrcene.

Differential regulation of calcium signalling pathways by components of Piper methysticum ('Awa).

Kava is a soporific, anxiolytic and relaxant in widespread ritual and recreational use throughout the Pacific. Traditional uses of kava by indigenous Pacific Island peoples reflect a complex pharmacopeia, centered on GABA-ergic effects of the well-characterized kavalactones. However, peripheral effects of kava suggest active components other than the CNS-targeted kavalactones. We have previously shown that immunocytes exhibit calcium mobilization in response to traditionally prepared kava extracts, and that the kavalactones do not induce these calcium responses. Here, we characterize the complex calcium-mobilizing activity of traditionally prepared and partially HPLC-purified kava extracts, noting induction of both calcium entry and store release pathways. Kava components activate intracellular store depletion of thapsigargin-sensitive and -insensitive stores that are coupled to the calcium release activated (CRAC) current, and cause calcium entry through non-store-operated pathways. Together with the pepper-like potency reported by kava users, these studies lead us to hypothesize that kava extracts contain one or more ligands for the transient receptor potential (TRP) family of ion channels. Indeed, TRP-like conductances are observed in kava-treated cells under patch clamp. Thus TRP-mediated cellular effects may be responsible for some of the reported pharmacology of kava.

The psychological wellbeing of patients following excision of a pilonidal sinus.

OBJECTIVE: To explore the effects of a pilonidal sinus wound on patients' psychological wellbeing. METHOD: An interpretive descriptive approach, using the Model of Living conceptual framework, guided data collection and analysis. The Model of Living was chosen to elicit information on how a pilonidal sinus wound affected activities of living. Participants were recruited from a database of a community nursing service, using purposive sampling, until data saturation was evident. Semi-structured interviews were used to collect the data. Data were examined for frequent patterns, which were organised into themes. RESULTS: Seven males and four females with ages ranging 17-39 years were selected through purposive sampling. Five participants reported that their wound affected their psychological wellbeing. Three themes and eight sub themes were identified from the data: adaption, perception and control. Depression and stress were associated with pain, physical inactivity, body weight changes and delayed wound healing. CONCLUSION: A pilonidal sinus wound can affect the psychological wellbeing of patients through pain,physical inactivity, changed body weight and delayed wound healing. Pre-existing conditions could also be exacerbated by the wound.

Nuclear DNA identification of migrating bull trout captured at the Puget Sound Energy diversion dam on the White River, Washington State.

Bull trout (Salvelinus confluentus) is a char listed as threatened under the United States Endangered Species Act throughout its range in the coterminous United States. Substantial morphological similarities between bull trout and Dolly Varden (S. malma) make field identification difficult. This has resulted in an incomplete understanding of their distribution and abundance in Washington State where these two species occur sympatrically. We used three diagnostic nuclear loci to determine the species of char collected at a trap on the White River in southern Puget Sound (Washington State, USA). Each of the 104 samples revealed the expected bull trout genotype at all three loci. This work presents three principle results: (i) the presence of a migratory bull trout population in southern Puget Sound; (ii) no evidence of migratory Dolly Varden over 3 years; and (iii) no evidence of hybridization was detected. These results also demonstrate how molecular markers can provide information essential to the conservation and management of these species.

Feeding of the 232Th levels from the decay of 236U.

Population of the 6+ 332 keV level in 232Th from the decay of 236U was observed for the first time. The 49, 112, and 171 keV gamma-ray energies and relative intensities from the decay of 236U were measured.

Milk intake and energy expenditure of free-ranging northern fur seal, Callorhinus ursinus, pups.

Milk ingested by mammalian offspring, coupled with offspring's utilization of this energetic investment, influences survival and growth. A number of studies have examined milk intake in otariids, but few have examined milk intake over the entire lactation period, and none has independently measured energy expenditure concurrent with milk intake. We concurrently examined milk intake, field metabolic rate (FMR), and body composition of 41 pups over the entire lactation interval in 1995 and 1996 on St. Paul Island, Alaska. One hundred two metabolic measurements were obtained with isotope dilution methods. Mean milk intake did not differ annually but increased with age and mass, ranging from 3,400+/-239 to 6,780+/-449 (+/-SE) mL per suckling bout. Milk energy consumption did not vary with age on a mass-specific basis. No differences were detected in milk volume consumed by male and female pups, either absolutely or on a mass-specific basis. Mass-specific FMR peaked during molting, was lowest postmolt, and did not vary by sex. Pups in 1995 had lower FMR than pups in 1996 and were also fatter. Mean milk energy utilized for maintenance metabolism decreased over time from 77% to 43% in 1995 and remained at 71% in 1996. Pup body mass was negatively correlated with the percentage of total body water and positively correlated with the percentage of total body lipid (TBL). Pups increased the percentage of TBL from 16% to 37%. Northern fur seal pups increased energy intake over lactation, while concurrent changes in body composition and pelage condition resulted in mass-specific metabolic savings after the molt.

Imaging of the internal carotid artery: the dilemma of total versus near total occlusion.

PURPOSE: To evaluate ultrasonography (US) and magnetic resonance (MR) angiography in the differentiation between occlusion and near occlusion of internal carotid artery (ICA). MATERIALS AND METHODS: Consecutive patients with occlusion or near occlusion of ICA at catheter angiography and who underwent MR angiography and US were included. MR angiography and US were compared with catheter angiography, the standard, for the ability to help distinguish occlusion from near occlusion. Noninvasive examinations were evaluated for the ability to classify near occlusions as having severe focal stenosis with distal luminal collapse versus diffuse nonfocal disease. The 95% CIs were calculated. RESULTS: In 55 of 274 patients with 548 ICAs, catheter angiography depicted 37 total occlusions and 21 near occlusions. US depicted all total occlusions; MR angiography depicted 34 (92%) (95% CI: 0.78, 0.98). US depicted 18 (86%) of 21 (95% CI: 0.64, 0.97) near occlusions; MR angiography depicted all (100%). Of 18 vessels that were determined to be patent at US, 17 (94%) (95% CI: 0.73, 0.99) were classified as having focal stenosis or diffuse disease. Because flow gaps were identified in vessels with focal and diffuse disease, MR angiography was not effective in helping to differentiate these lesions. CONCLUSION: Assuming US is the initial imaging examination, when occlusion is diagnosed, MR angiography can depict it. If occlusion is confirmed, no further imaging is necessary. US performed well in helping to differentiate vessels with focal severe stenosis from those with diffuse disease. MR angiography added little in this group. Catheter angiography remains beneficial for vessels with diffuse nonfocal narrowing.

Combined carotid endarterectomy and coronary bypass: a decade experience at UCLA.

PURPOSE: The purpose of this review was to determine outcomes for combined carotid endarterectomy (CEA) and coronary revascularization (CABG) in patients with asymptomatic carotid stenosis. METHODS: We reviewed the medical records of consecutive combined procedures (CEA and CABG), performed at UCLA Medical Center from October, 1989 to January, 1999. FINDINGS: There were 43 patients, 27 men and 16 women, with a mean age of 71 yr (range 51-87). Thirty-four patients 79% (34/43) had asymptomatic carotid stenosis. Stroke occurred in three patients (3/43 = 6.9%). Stroke ipsilateral to the CEA occurred in two patients: one asymptomatic (1/34 = 2.9%) and one symptomatic (1/9 = 11.1%). CONCLUSIONS: The majority of patients undergoing combined CEA/CABG have asymptomatic carotid stenosis identified in preparation for elective CABG. The asymptomatic carotid subset stroke rate of 2.9% resulting from a combined CEA/CABG is higher than our reported rate for CEA performed alone. In patients with asymptomatic carotid stenosis, the combined procedure should be selectively performed.

Carotid endarterectomy with normal findings from a completion study: Is there need for early duplex scan?

OBJECTIVE: The objective of this study was to determine the value of early (< 6 months) duplex scanning after carotid endarterectomy (CEA) with an intraoperative completion study with normal results. Attention was paid to restenosis rates and reoperation for recurrent stenosis within the first 6 months. METHODS: A retrospective review was performed on 380 CEAs (338 patients) with intraoperative completion studies and duplex surveillance within the first 6 months. Results of completion studies, restenosis rates, and recurrent symptoms were evaluated for each operation. Studies were performed from 0 to 200 days postoperatively (median, 28). RESULTS: Intraoperative completion studies included 333 angiograms, 26 duplex scans, and 21 angiograms with duplex scans. Of the 380 intraoperative completion studies, 28 (7.5%) had abnormal findings, including 14 abnormal internal carotid arteries (ICAs). Twenty-four procedures were revised, and the findings of all repeat completion studies were normal. Of the initial completion studies, in four cases, abnormalities (3 ICAs) were insignificant and did not warrant further intervention. Follow-up ICA duplex scans had normal results after 364 (95.8%) CEAs. There were 14 mild recurrent ICA stenoses and two moderate recurrent ICA stenoses; neither had abnormal findings from the completion study. There were no severe recurrent ICA stenoses. External carotid artery (ECA) recurrent stenosis included 7 mild, 15 moderate, and 9 severe restenoses. CONCLUSIONS: Only 0.5% of CEAs developed moderate restenosis. No procedures had severe recurrent stenosis on duplex scan within the first 6 months, and none required intervention. Duplex surveillance in the first 6 months is relatively unproductive, providing that there were normal results from an intraoperative completion study for each patient. Routine surveillance can be started at 1 year.

Cardiac morbidity and mortality following carotid endarterectomy: the importance of diabetes and multiple Eagle risk factors.

The objectives of this study were to (1) determine cardiac morbidity and mortality in patients undergoing carotid endarterectomy (CEA) and (2) to determine whether any Eagle risk factors and/or the indication for CEA are associated with a higher risk of an adverse cardiac event. The records of 123 male patients who underwent CEA were retrospectively reviewed. The Eagle risk factors for adverse cardiac events, indications for CEA, and adverse cardiac events were recorded and analyzed. In males undergoing CEA, the presence of diabetes or multiple Eagle risk factors significantly increases the risk of an adverse postoperative cardiac event. There is no difference in cardiac event rate between symptomatic and asymptomatic CEA. Thus, asymptomatic CEA should be approached with caution in these higher cardiac risk patients.

Penetrating ulceration of the infrarenal aorta: case reports of an embolic and an asymptomatic lesion.

Penetrating aortic ulceration is uncommon in the infrarenal aorta. We describe a patient with a penetrating infrarenal aortic ulcer manifesting as blue toe syndrome, and a second patient with a similar lesion identified as an incidental finding. These two patients were treated for penetrating infrarenal aortic ulceration within the past 9 months at two university-affiliated hospitals, a regional Veterans Administration Medical Center, and a County Medical Center. Both lesions demonstrated aneurysm changes with varying degrees of mural thrombus. The lesion filled with fresh thrombus proved labile, with embolization manifesting as blue toe syndrome. We support the aggressive treatment of aneurysmal penetrating aortic ulcer with aortic graft replacement to eliminate the potential for distal embolization and to obviate the risk of rupture and death.

Dipyridamole-thallium/sestamibi before vascular surgery: a prospective blinded study in moderate-risk patients.

PURPOSE: This study assessed in a prospective, blinded fashion whether a reversible defect on dipyridamole-thallium (DTHAL)/sestamibi (DMIBI) can predict adverse cardiac events after elective vascular surgery in patients with one or more clinical risk factors. METHODS: Consecutive patients with one or more clinical risk factors underwent a preoperative blinded DTHAL/DMIBI. Patients with recent congestive heart failure (CHF) or myocardial infarction (MI) or severe or unstable angina were excluded. RESULTS: Eighty patients (78% men; mean age, 65 years) completed the study. Diabetes mellitus was the most frequent clinical risk factor (73%), followed by age older than 70 years (41%), angina (29%), Q wave on electrocardiogram (26%), history of CHF (7%), and ventricular ectopy (3%). The results of DTHAL/DMIBI were normal in 36 patients (45%); a reversible plus or minus fixed defect was demonstrated in 28 patients (36%), and a fixed defect alone was demonstrated in 15 patients (19%). Nine adverse cardiac events (11%) occurred, including three cases of CHF, and one case each of unstable angina, Q wave MI, non-Q wave MI, and cardiac arrest (successfully resuscitated). Two cardiac deaths occurred (2% overall mortality), one after a Q wave MI and one after CHF and a non-Q wave MI. The cardiac event rate was 14% for reversible defect and 9.8% without reversible defect (P =.71). The cardiac event rate was 12.5% (one of eight cases) for two or more reversible defects, versus 11.1% (eight of 72 cases) for fewer than two reversible defects (P = 1.0). The sensitivity rate of two or more areas of redistribution was 11% (95% CI, 0.3%-48%), the specificity rate was 90%, and the positive and negative predictive values were 12.5% and 89%, respectively. CONCLUSION: Our study demonstrated no association between reversible defects on DTHAL/DMIBI and adverse cardiac events in moderate-risk patients undergoing elective vascular surgery.

Acquisition, extinction, and reinstatement of Pavlovian fear conditioning: the roles of the NMDA receptor and nitric oxide.

The acquisition and extinction of Pavlovian conditioned fear have been shown to be mediated by the N-methyl-D-aspartate (NMDA) glutamate receptor. This study found that the NMDA antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine maleate (MK-801) blocked the reinstatement of Pavlovian conditioned fear in rats. The role of nitric oxide (NO) in the acquisition and extinction of Pavlovian fear conditioning was also examined. L-NAME, an NO synthase inhibitor, failed to block the acquisition or extinction of Pavlovian fear conditioning. The results are discussed in the context of hierarchical associations and the array of NMDA and calcium mediated mechanisms of synaptic strengthening.

The ontogeny of metabolic rate and thermoregulatory capabilities of northern fur seal, Callorhinus ursinus, pups in air and water.

Young pinnipeds, born on land, must eventually enter the water to feed independently. The aim of this study was to examine developmental factors that might influence this transition. The ontogeny of metabolic rate and thermoregulation in northern fur seal, Callorhinus ursinus, pups was investigated at two developmental stages in air and water using open-circuit respirometry. Mean in-air resting metabolic rate (RMR) increased significantly from 113+/-5 ml O(2 )min(-)(1) (N=18) pre-molt to 160+/-4 ml O(2 )min(-)(1) (N=16; means +/- s.e.m.) post-molt. In-water, whole-body metabolic rates did not differ pre- and post-molt and were 2.6 and 1.6 times in-air RMRs respectively. Mass-specific metabolic rates of pre-molt pups in water were 2.8 times in-air rates. Mean mass-specific metabolic rates of post-molt pups at 20 degrees C in water and air did not differ (16.1+/-1.7 ml O(2 )min(-)(1 )kg(-)(1); N=10). In-air mass-specific metabolic rates of post-molt pups were significantly lower than in-water rates at 5 degrees C (18.2+/-1.1 ml O(2 )min(-)(1 )kg(-)(1); N=10) and 10 degrees C (19.4+/-1.7 ml O(2 )min(-)(1 )kg(-)(1); N=10; means +/- s.e.m.). Northern fur seal pups have metabolic rates comparable with those of terrestrial mammalian young of similar body size. Thermal conductance was independent of air temperature, but increased with water temperature. In-water thermal conductance of pre-molt pups was approximately twice that of post-molt pups. In-water pre-molt pups matched the energy expenditure of larger post-molt pups while still failing to maintain body temperature. Pre-molt pups experience greater relative costs when entering the water regardless of temperature than do larger post-molt pups. This study demonstrates that the development of thermoregulatory capabilities plays a significant role in determining when northern fur seal pups enter the water.

Ability to use duplex US to quantify internal carotid arterial stenoses: fact or fiction?

PURPOSE: To determine if duplex ultrasonography (US) can help predict the degree of internal carotid arterial (ICA) stenosis. MATERIALS AND METHODS: ICA peak systolic velocity (PSV) and the ratio of the PSV in the ICA to that in the ipsilateral common carotid artery (VICA/VCCA) were compared with the degree of arteriographically measured stenosis. ICAs were arteriographically subgrouped at 10% incremental levels of stenosis and broader ranges. Mean PSV, VICA/VCCA, and SDs were calculated for each category. Histograms showing the numbers of stenotic ICAs in subgroups and for vessels with stenoses of greater than or equal to or less than 70% narrowing were constructed. The number of vessels correctly subgrouped with typical Doppler US thresholds was calculated. RESULTS: Mean PSV and VICA/VCCA increased with stenosis level (P < .01); SDs were wide. Histograms showed Doppler US values in the central groups across all disease levels. Histograms differentiating at least or less than 70% stenosis showed minimal overlap. PSV and VICA/VCCA helped classify, respectively, 185 and 181 of 204 vessels with stenoses of less than 50%, 15 and 21 of 46 vessels with stenoses of 50%-69%, and 73 and 67 of 84 vessels with stenoses of 70% or greater. When classifying stenoses as 69% or less or 70% or more, PSV and VICA/VCCA were correct in 90.6% and 90.3% of vessels. CONCLUSION: Doppler US is excellent for classifying stenoses as above or below a single degree of severity but does not function well in stenosis subclassification.

Doppler sonographic parameters for detection of carotid stenosis: is there an optimum method for their selection?

OBJECTIVE: A wide range of Doppler threshold values for carotid stenosis is found in the literature. We undertook this study to compare methods of derivation and to determine if an optimum strategy of threshold selection exists for a high-risk population. MATERIALS AND METHODS: From the sonograms of all patent internal carotid arteries, peak systolic velocity in the internal carotid artery (ICA(PSV)) and the ratio of peak systolic velocity in the internal carotid artery to that of the common carotid artery (ICA(PSV)/ CCA(PSV)) were compared with the percentage of angiographically determined stenosis. Receiver operating characteristic curves were generated for levels of stenosis > or =60% and > or =70%. Doppler thresholds were chosen on the basis of maximum accuracy and on the basis of > or =90% sensitivity and specificity. Patients were then segregated into symptomatic and asymptomatic cohorts, and the above process was repeated. An effectiveness analysis was also conducted using various Doppler thresholds. Thresholds derived using these three methods were compared and optimal values chosen. RESULTS. Of 333 carotid arteries that fit inclusion criteria, 132 were found in asymptomatic patients and 201 in symptomatic patients. Maximum accuracy, > or =90% sensitivity and specificity, and effectiveness analysis each produced different ranges of thresholds. We chose final thresholds that maintained patient outcome profiles. For asymptomatic patients at the > or =60% stenosis level, thresholds were ICA(PSV) = 200 cm/sec and ICA(PSV)/CCA(PSV) = 3.0. For symptomatic patients with stenosis > or =70%, thresholds were ICA(PSV) = 175 cm/sec and ICA(PSV)/CCA(PSV) = 2.5. CONCLUSION: Considerable latitude exists in the choice of carotid Doppler thresholds. We propose a rational strategy for threshold selection based on a combination of three commonly used methods. Our observations indicate that it appears advisable to consider symptomatic and asymptomatic patients separately and to apply appropriately derived thresholds.

The hormonal coordination of behavior and physiology at adult ecdysis in Drosophila melanogaster.

In insects, ecdysis is thought to be controlled by the interaction between peptide hormones; in particular between ecdysis-triggering hormone (ETH) from the periphery and eclosion hormone (EH) and crustacean cardioactive peptide (CCAP) from the central nervous system. We examined the behavioral and physiological functions of the first two of these peptides in Drosophila melanogaster using wild-type flies and knockout flies that lacked EH neurons. We used ETH from Manduca sexta (MasETH) to induce premature ecdysis and compared the responses of the two types of flies. The final release of EH normally occurs approximately 40 min before ecdysis. It is correlated with cyclic guanosine monophosphate (cGMP) production in selected neurons and tracheae, by an elevation in the heart rate and by the filling of the new tracheae with air. Injection of developing flies with MasETH causes all these events to occur prematurely. In EH cell knockouts, none of these changes occurs in response to MasETH, and these flies show a permanent failure in tracheal filling. This failure can be overcome in the knockouts by injecting them with membrane-permeant analogs of cGMP, the second messenger for EH. The basis for the 40 min delay between EH release and the onset of ecdysis was examined by decapitating flies at various times relative to EH release. In flies that had already released EH, decapitation was always followed within 1 min by the start of ecdysis. Immediate ecdysis was never observed when the EH cell knockout flies were decapitated. We propose that EH activates both ventral central nervous system elements necessary for ecdysis (possibly the CCAP cells) and descending inhibitory neurons from the head. This descending inhibition establishes a delay in the onset of ecdysis that allows the completion of EH-activated physiological processes such as tracheal filling. A waning in the inhibition eventually allows ecdysis to begin 30-40 min later.

Can prism adaptation for acquired esotropia be accomplished in a shorter time frame?

PURPOSE: Results of the Prism Adaptation Study (PAS) indicated that surgical success rates were highest when augmented surgery was performed for the increased angle of deviation in the prism adaptation responders who underwent surgery for the prism-determined angle of esotropia. The purpose of this study was to see if the prism adaptation response process could be performed in a shorter time span than dictated in the PAS protocol (minimum, 4-7 days). METHODS: After the prescription of appropriate spectacles, patients with acquired stable esotropia were prism adapted and then reexamined and readapted if necessary at 24 hours and 4 to 7 days. The 4- to 7-day visit was the determining visit in the PAS. The question in this study was whether the 24-hour visit would provide the same end point and allow adaptation in a shorter period of time. In addition, a motor end point was used in this study, whereas in the PAS, the end point was both motor and sensory. RESULTS: Thirty-two patients met the entry criteria. Nineteen of the 32 patients built up their entry angle during the prism adaptation process. Thirty of the 32 patients who left the office stable at the 24-hour visit remained stable at the 4- to 7-day visit. CONCLUSION: If the 4- to 7-day visit is used as the "gold" standard, 94% of the patients in this study would not have benefited from a longer (beyond 24 hours) wear time of prisms. With the use of motor stability, prism adaptation can be carried out in a reproducible and timely fashion.

Cardiac morbidity and operative mortality following lower-extremity amputation: the significance of multiple Eagle criteria.

The ability of the Eagle criteria (age >70 years, angina, diabetes, Q wave on EKG, history of congestive heart failure) to predict adverse cardiac events following major vascular surgery has previously been demonstrated. However, the utility of these criteria for lower-extremity amputation is not well established. To determine the value of the Eagle criteria for predicting cardiac morbidity and operative mortality following major lower-extremity amputation, we reviewed 214 consecutive procedures performed at two institutions over a 3-year period. Mean age was 62.7 years and 85% of the patients were male. Diabetes was the most frequent Eagle criterion (74%). The mean number of Eagle criteria was 1.6. Fifty-six percent of the amputations were below the knee, 24% were above the knee, and 20% were guillotine. On multivariate regression analysis, the presence of two or more Eagle criteria (16% vs. 4%, p = 0.04) and decompensated heart failure (39% vs. 7%, p = 0.003) were predictive of adverse cardiac events. The only predictor of postoperative mortality was the presence of two or more Eagle criteria (15% vs. 4%, p = 0.004). Our evaluation of the results of this study led us to conclude that patients requiring major lower-extremity amputation for major vascular disease who have multiple Eagle criteria or decompensated congestive heart failure are at high risk for adverse cardiac events and postoperative death. These findings should be used to guide perioperative cardiac evaluation and therapy.