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.

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.

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.

Agreement between grating acuity at age 1 year and Snellen acuity at age 5.5 years in the preterm child. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

PURPOSE: To examine the relation between grating acuity at age 1 year and Snellen acuity and grating acuity at 5.5 years, in preterm children with birth weights less than 1251 g. METHODS: Subjects were participants in the multicenter study of Cryotherapy for Retinopathy of Prematurity. The Teller acuity card (TAC; Vistech Consultants, Dayton, OH) procedure was used to measure monocular grating acuity in children at ages 1 and 5.5 years. Early-treatment diabetic retinopathy study (ETDRS) charts were used to measure the childrens' monocular recognition (Snellen) acuity at age 5.5 years. Data are presented for 575 eyes with measurable TAC grating acuity at 1 year and 111 eyes that had no measurable acuity at 1 year. RESULTS: Among eyes with normal acuity at 1 year, 86.8% showed normal Snellen acuity, and 94.3% showed normal grating acuity at 5.5 years. Among eyes that were blind (i.e., had no measurable TAC grating acuity) at 1 year, 96.8% showed no quantifiable Snellen acuity, and 89.2% showed no quantifiable grating acuity at 5.5 years. Only 2.4% of eyes had acuity in the range between normal and blind at 1 year (i.e., measurable grating acuity <1.6 cyc/deg); thus, the predictive value of acuity scores in this range could not be determined. Correlation analysis indicated that the relative position within the normal range of an eye's grating acuity score at 1 year was not predictive of the relative position within the normal range of that eye's acuity score at 5.5 years. CONCLUSIONS: Among a large population of low-birth-weight infants, eyes with normal grating acuity at age 1 year generally showed normal Snellen and grating acuity at age 5.5 years, and eyes that had no quantifiable acuity at 1 year remained blind at 5.5 years. Relative position of an eye's acuity score within the normal range was not predictive of the relative position of that eye's later acuity score.

Challenge differentially affects cytokine production and metabolic status of growing and finishing swine.

Growing (35 kg body weight) and finishing (85 kg body weight) swine challenged with endotoxin (Escherichia coli O55:B5) at a dose of either 2 or 20 microg/kg produced tumor necrosis factor (TNF)alpha in a dose-response relationship as measured by bioassay. Peak TNFalpha plasma levels were observed 1-2 hr post-challenge, returning to basal values 4 hr post-challenge. However, both an enzyme-linked immunosorbent assay specific for swine TNFalpha and total human TNFalpha demonstrated no dose-response relationship; peak plasma levels of immunoreactive TNFalpha were also observed 1-2 hr post-challenge. Maximal plasma interleukin-6 levels occurred 1-2 hr post-challenge and remained elevated through 8 hr post-challenge; there was no effect of lipopolysaccharide dose or metabolic status. Although the metabolic status of the animals also affected glucose levels, with growing animals exhibiting greater sensitivity compared with finishing animals, endotoxin-induced decreases in blood glucose levels were primarily dose-dependent. In contrast, changes in plasma urea nitrogen and free fatty acid (FFA) levels were strictly related to the metabolic status. Urea nitrogen levels were unchanged in growing swine, whereas they were increased in finishing swine and remained elevated 24 hr post-challenge. FFA levels in growing and finishing swine increased 3-6 hr post-challenge. FFA levels returned to basal values for finishing swine 24 hr post challenge, but in growing swine remained elevated 24 hr post-challenge. Plasma aspartate transaminase levels were increased through 24 hr post-challenge; animals given a dose of 20 microg/kg exhibited the greatest increase. Similarly, swine challenged with a dose of 20 microg/kg also exhibited the greatest increase in levels of conjugated bilirubin; there was no effect on unconjugated (free) bilirubin. These results demonstrate that endotoxin challenge of swine result in a pattern of changes that are dependent on both the dose of endotoxin used and the metabolic status of the animal examined.

Pharyngeal flap necrosis as a cause of airway obstruction during induction of anesthesia.

Anesthesiologists should approach the airway carefully in the patient with a diagnosis of head and neck carcinoma, particularly if the patient has had previous surgery and reconstruction. Patients with head and neck carcinoma may be difficult intubations due to altered anatomy from the tumor or fibrotic changes because of radiation therapy. Our patient had had pharyngectomy and reconstruction with a pectoralis major skin flap. The patient returned to the operating suite for wide-excision pharyngectomy and had acute airway obstruction after induction of general anesthesia. The pectoralis flap had necrosed, pulling away from the pharyngeal wall and obstructing the patient's glottic opening.

Recommended standards for reports dealing with lower extremity ischemia: revised version.

Recommended standards for analyzing and reporting on lower extremity ischemia were first published by the Journal of Vascular Surgery in 1986 after approval by the Joint Council of The Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery. Many of these standards have been accepted and are used in the current literature on peripheral arterial occlusive disease. With the passage of time, some oversights, aspects that require clarification, and better modifications have been recognized. This report attempts to correct these shortcomings while reinforcing those recommendations that have proven satisfactory. Explanatory comments are added to facilitate understanding and application. This version is intended to replace the original version.

Asymptomatic carotid artery stenosis screening in patients with lower extremity atherosclerosis: a prospective study.

Eighty-nine male veterans presenting to a vascular surgery clinic with symptomatic lower extremity atherosclerosis were prospectively screened by duplex scan for asymptomatic carotid artery stenosis (CAS). Their chief complaint was: claudication (90%), rest pain (6%), and ischemic ulcer or gangrene (4%). The mean ankle-brachial index (ABI) was 0.77. Twenty-five CAS > 50% were detected in 18 (20%) patients. Twelve CAS > 75% were detected in 11 (12%) patients. There was no difference between patients with and without CAS > 50% with regards to mean ABI, history of angina, diabetes, hypertension, prior coronary artery bypass, or history of smoking. Carotid bruit was associated with ipsilateral CAS > 50% [p < 0.0001, sensitivity (52%), specificity (88%), positive predictive value (41%), negative predictive value (92%)]. As a result of the screening, eight elective carotid endarterectomies have been performed to date in six (7%) patients with one transient twelfth cranial nerve paresis as the only postoperative complication. We conclude that: (1) male patients presenting with symptomatic lower extremity atherosclerosis have a 20% prevalence of asymptomatic CAS > 50%, (2) there is no correlation between the degree of lower extremity ischemia and CAS > 50%, (3) carotid bruit is significantly associated with CAS > 50%, but has a low sensitivity, and (4) routine CAS screening should be considered for all male patients with symptomatic lower extremity atherosclerosis regardless of whether a bruit is present.

Abdominal aortic aneurysm screening in elderly males with atherosclerosis: the value of physical exam.

The purpose was 1) To assess the prevalence of abdominal aortic aneurysms (AAA) in elderly males with atherosclerosis and 2) to evaluate the value of physical exam (PE) by a vascular surgeon in detecting AAA. A total of ninety-six males older than 55 years referred to vascular surgery clinic with atherosclerotic disease were screened prospectively with PE by a vascular surgeon, followed by ultrasonography (US). Atherosclerosis was documented by ankle brachial index and duplex US. Patients who had recently undergone a vascular procedure, aortography, laparotomy, abdominal computed tomography, or US were excluded. Mean age was 67 years. Patients were 67 per cent Caucasian, 32 per cent black, and 1 per cent Hispanic. Presenting complaints were related to claudication (83%), carotid disease (19%), both (3%), and subclavian stenosis (1%). Patient characteristics included cigarette smoking (85%), hypertension (67%), cardiac disease (51%), diabetes (45%), stroke (18%), and chronic obstructive pulmonary disease (8%). One (1%) 3.7 cm AAA was detected by US. Sensitivity of PE was 100 per cent and specificity 92 per cent. Twenty-two (23%) patients were too obese for us to feel the aortic pulse. Screening cost was $14,250. The prevalence of AAA in this population is very low. AAA screening should be reserved for patients with a positive PE or who are too obese for the examiner to feel the aortic pulse.

Intraoperative vascular endoscopy: early and late results.

In a prospective study, 60 consecutive cases of vascular endoscopy were analyzed to examine the role of angioscopy in infrainguinal vascular procedures. A total of 52 patients had 60 separate vascular endoscopy procedures performed as an adjunct to various vascular procedures; results of intraoperative arteriography were available in 38 of 60 cases. All patients were followed for at least 42 months. The 19 patients who underwent thrombectomy with angioscopy were compared with 19 age-matched control subjects who underwent infrainguinal thrombectomy without angioscopy to evaluate the influence of angioscopy on primary and secondary patency rates. Angioscopy allowed observation of 50 lesions; angiography failed to detect three. These findings altered surgical management in 24 cases (40%). Primary patency rates for the control and experimental thrombectomy groups were 38.8% and 6.5% at 42 months, respectively (p = 0.010 based on log-rank test). Secondary patency rates for the control and experimental groups at 42 months were 63.8% and 49%, respectively (p = 0.521). The limb salvage rate was 89% at 42 months for both groups (p = 0.973). Angioscopy provides the clinician with a direct view while he or she is performing vascular procedures. However, there was no statistical improvement in secondary patency and limb salvage rates. Furthermore, the use of angioscopy during thrombectomy may increase the propensity for subsequent intervention as evidenced by the frequency of changes in surgical management and the lower primary patency rate.