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The objective of this study was to compare the categorizations and determinants related to remodeling by the three definitions commonly used. Several morphological and intravascular ultrasound (IVUS) studies have demonstrated the fundamental importance of arterial remodeling in atherosclerosis. However, lack of consensus on how to define remodeling has led to conflicting analyses of factors that influence this process. Analysis of pre-interventional IVUS images of 514 lesions in native coronary arteries was performed. Arterial remodeling was defined as outward by definition 1, when [cross-sectional area (CSA) of the external elastic membrane (EEM) at the lesion site (EEM(lesion))]/[EEM CSA either at the proximal (EEM(prox ref)) or distal (EEM(distal ref)) reference site with the least amount of plaque] was > 1.05, intermediate when this ratio was between 0.95 and 1.05, and inward when < 0.95. Remodeling was defined as outward by definition 2 when EEM(lesion) > both EEM(prox ref) and EEM(distal ref), inward when EEM(lesion) < both EEM(prox ref) and EEM(distal ref), and intermediate when EEM(lesion) was intermediate between EEM(prox ref) and EEM(distal ref). By definition 3, vessel remodeling was defined as outward when EEM(lesion) > (EEM(prox ref) + EEM(distal ref))/2 and intermediate/inward when EEM(lesion) < or = (EEM(prox ref) + EEM(distal ref))/2. The frequency of outward remodeling was significantly higher by definitions 1 and 3 than by definition 2, whereas a higher frequency of inward remodeling was observed in definition 1, resulting in significantly different remodeling distributions between the three definitions (P < 0.0001). By multivariate logistic analysis, the only clinical determinants related to outward remodeling was younger age, and only by definition 3. IVUS determinants varied significantly between the three definitions. The only consistent determinants among the three definitions were smaller lumen CSA at the reference site and larger plaque + media CSA at the lesion site. This study demonstrates the significant impact of different remodeling definitions on the incidence and determinants of remodeling patterns. The marked variability in categorization of remodeling underscores the importance of developing a standard methodology., (Copyright 2005 Wiley-Liss, Inc)

Epithelial ovarian cancer is the most frequent cause of gynecologic malignancy-related mortality in women. To identify genes up-regulated in ovarian cancer, PCR-select cDNA subtraction was done and Drosophila Eyes Absent Homologue 2 (EYA2) was isolated as a promising candidate. The transcriptional coactivator eya controls essential cellular functions during organogenesis of Drosophila. EYA2 mRNA was found to be up-regulated in ovarian cancer by real-time reverse transcription-PCR, whereas its protein product was detected in 93.6% of ovarian cancer specimens by immunohistochemistry (n = 140). EYA2 was amplified in 14.8% of ovarian carcinomas, as detected by array-based comparative genomic hybridization (n = 88). Most importantly, EYA2 overexpression was significantly associated with short overall survival in advanced ovarian cancer (n = 99, P = 0.0361). EYA2 was found to function as transcriptional activator in ovarian cancer cells by Gal4 assay and to promote tumor growth in vivo in xenograft models. Therefore, this study suggests an important role of EYA2 in ovarian cancer and its potential application as a therapeutic target.

Low flow (LF) promotes late lumen loss after angioplasty by exacerbating inward remodelling through redox-sensitive mechanisms. Stents eliminate inward remodelling and the effect of LF on in-stent restenosis is uncertain. We performed over-sized (1.3-1.5:1) stenting (S) and balloon injury (in the same vessel, B) to the carotid arteries of cholesterol-fed rabbits and compared 28-day late lumen loss with that in an uninjured segment in the same vessel (U). Vessels (n = 5 animals per group) were subjected to high (H), normal (N) and low (L) flow in animals fed either vehicle (V) or the antioxidant pyrrolidine dithiocarbamate, PDTC (P). LF significantly increased in-stent neointima formation relative to normal and high flow (SLV 0.72 +/- 0.07 mm(2) versus SNV 0.43 +/- 0.08 mm(2) versus SHV 0.28 +/- 0.04 mm(2), P < 0.05). However, LF resulted in greater lumen loss in segments from the same vessel subject to balloon injury (lumen SLV 5.18 +/- 0.40 mm(2) and SNV 5.32 +/- 0.40 mm(2) versus BLV 1.28 +/- 0.33 mm(2) and BNV 2.19 +/- 0.28 mm(2)), by greater enhancement of inward remodelling. In addition, inward remodelling and lumen loss due to LF were greater in balloon-injured segments than in adjacent uninjured segments where shear homeostatic remodelling occurs (lumen BLV 1.28 +/- 0.33 mm(2) versus ULV 1.52 +/- 0.22 mm(2)). Lastly, while PDTC effectively reduced intima formation and inward remodelling due to LF in balloon-injured vessels there was no effect on flow-dependent neointima formation in stented vessels. We conclude that LF accentuates in-stent neointima formation, but that flow-dependent lumen loss after stenting is less than that after balloon injury. When LF is present lumen loss can be minimised by antioxidants or stenting.

Background: Mutations in BRAF have recently been identified in a significant percentage of primary and metastatic cutaneous malignant melanomas. As ultraviolet (UV) exposure may play a role in the development of cutaneous melanoma lesions with BRAF mutations, BRAF mutation frequency in melanomas arising in sites protected from sun exposure may be lower than those from sun-exposed areas. Thus, we determined the BRAF mutation frequency in a panel of 13 mucosal melanomas and compared those data with data from all currently published series of cutaneous melanomas., Methods: BRAF exon 15 DNA from 13 archival primary mucosal melanomas (eight vulvar, four anorectal, and one laryngeal) was sequenced using intron-based primers. As archival DNA occasionally produces poor-quality template, results were confirmed with a TspRI restriction fragment length polymorphism (RFLP) that distinguishes wild-type BRAF from the common mutant form V599E. A binomial test was used to compare the mutation frequency in the mucosal melanomas with the published mutation frequency in cutaneous melanomas., Results: None of the 13 mucosal melanomas in this series had an exon 15 BRAF mutation, as compared to 54/165 (33%) primary cutaneous melanomas with BRAF mutations in a compilation of all current published studies (p = 0.006)., Discussion: These data suggest that UV exposure, plays a role in the genesis of BRAF mutations in cutaneous melanoma, despite the absence of the characteristic C>T or CC>TT mutation signature associated with UV exposure, and suggests mechanisms other than pyrimidine dimer formation are important in UV-induced mutagenesis.

Hypothesis: The success of an educational program in July 1999 that lowered the catheter-related bloodstream infection (CRBSI) rate in our intensive care unit (ICU) 3-fold is correlated with compliance with "best-practice" behaviors., Design: Before-after trial., Setting: Surgical ICU in a referral hospital., Patients: A random sample underwent bedside audits of central venous catheter care (n = 187). All ICU admissions during a 39-month period (N = 4489) were prospectively followed for bacteremia., Interventions: On the basis of audit results in December 2000, a behavioral intervention was designed to improve compliance with evidenced-based guidelines of central venous catheter management., Main Outcome Measures: Compliance with practices known to decrease CRBSI. Secondary outcome was CRBSI rate on all ICU patients., Results: Multiple deficiencies were identified on bedside audits 18 months after the previous educational program. After the implementation of a separate behavioral intervention in July 2001, a second set of bedside audits in December 2001 demonstrated improvements in documenting the dressing date (11% to 21%; P<.001) and stopcock use (70% to 24%; P<.001), whereas nonsignificant trends were observed in hand hygiene (17% to 30%; P>.99) and maximal sterile barrier precautions (50% to 80%; P =.29). Appropriate practice was observed before and after the behavioral intervention in catheter site placement, dressing type, absence of antibiotic ointment, and proper securing of central venous catheters. Thirty-two CRBSIs occurred in 9353 catheter-days 24 months before the behavioral intervention compared with 17 CRBSIs in 6152 catheter-days during the 15 months after the intervention (3.4/1000 to 2.8/1000 catheter-days; P =.40)., Conclusions: Although a previous educational program decreased the CRBSI rate, this was associated with only modest compliance with best practice principles when bedside audits were performed 18 months later. A behavioral intervention improved all identified deficiencies, leading to a nonsignificant decrease in CRBSIs.

Pregnancy is a major life event for all women. However, when a psychiatric disorder is added to or exacerbated by the pregnancy then the problem requires expert knowledge from more than one area of medicine. This paper looks at pregnancy and the relationship with depression, eating disorders, and pathological fear of childbirth or tokophobia. It also examines the outcome for these women and their babies. Mental illness is a serious concern. It is now recognised that death from suicide is the leading cause of maternal death overall. Research in these areas is relatively sparse but an attempt is made to collate what is known.

We examined the effects of high cholesterol diet and pyrrolidine dithiocarbamate (PDTC) on flow-dependent remodeling after angioplasty. After right common carotid balloon-injury, the right external carotid (low flow) or left common carotid artery were ligated (high flow) in rabbits fed normal diet, 1% cholesterol diet without or with the antioxidant PDTC for 7 days pre- and 7-28 days post-injury. Angiographic lumen diameter was significantly greater at 28 days in high flow than low flow normal diet animals, attributable on perfusion-fixed vessel morphometry to altered remodeling (area within the external elastic lamina: high flow 1.85+/-0.24 vs. low flow 1.31+/-0.04 mm(2), P<0.05) rather than differences in neointima formation or vessel tone. In animals on 1% cholesterol diet high flow remodeling was significantly enhanced (area within the external elastic lamina 3.13+/-0.17 mm(2), P<0.05 vs. high flow normal diet) but low flow inward remodeling was similar (area within the external elastic lamina 1.29+/-0.07 mm(2)). Mean Doppler flow velocities (initial/post-ligation/28 day follow-up, cm/s) had almost normalized in normal diet animals (high flow 30/49/35, low flow 32/9/26) but showed overcompensation in 1% cholesterol diet animals (high flow 32/49/22, low flow 30/11/25). PDTC therapy markedly attenuated remodeling (area within the external elastic lamina: high flow 2.20+/-0.18, and low flow 2.00+/-0.11 both P<0.05 vs. 1% cholesterol diet alone) and flow velocities only partially normalized (high flow 26/42/34, low flow 27/7/16). We conclude that hypercholesterolemia enhances and PDTC attenuates flow-dependent remodeling after angioplasty.

Objectives: We sought to document whether a physiologic change in gender has any effect on coronary arterial size., Background: The coronary arteries are smaller in women, even after correction for body surface area (BSA). These differences may contribute to adverse clinical outcomes after coronary artery bypass graft surgery and myocardial infarction in women. In male and female transsexuals, pharmacologic doses of estrogens and androgens significantly influence vascular diameter. Thus, gender differences in the coronary vasculature may be a reflection of the hormonal environment., Methods: In 86 patients who had undergone orthotopic heart transplantation, serial intravascular ultrasound studies of the proximal left anterior descending coronary artery (LAD) were analyzed. Changes in vessel area (VA) over the first or second post-transplant year were recorded, and comparisons were made between donor hearts that were transplanted in a patient of the same gender and those that were transplanted in a patient of the opposite gender., Results: Vessel area of the proximal LAD increased over time in all patient groups. In hearts transplanted within the same gender and in male donor hearts transplanted to female recipients, the change was small and not significant. However, in hearts transplanted from female donors to male recipients, there was a substantial and highly significant increase in LAD VA (median 16.13 to 17.88 mm(2); p = 0.01). This increase was not explained by confounding due to changes in BSA or left ventricular wall thickness., Conclusions: This pattern of arterial remodeling early after heart transplantation supports a link between host gender and coronary arterial size.

Objectives: This study was designed to assess the prevalence and clinical significance of exaggerated nonculprit lesion stenosis in the setting of acute (<12 h) myocardial infarction (AMI)., Background: Although microvascular spasm may reduce nonculprit artery flow during AMI, it is unknown whether increased tone may exaggerate nonculprit lesion severity., Methods: In patients with additional angiography within nine months of AMI, and significant nonculprit lesions imaged in matching views, stenosis severity was compared between studies in a random blinded fashion using validated quantitative coronary angiography software. Baseline demographics, medications, hemodynamics at each study, and clinical status at follow-up (infarct/unstable angina/stable angina) were used to determine the independent influence of the infarct presentation on stenosis exaggeration., Results: From 548 patients with AMI (1/99 to 6/01, 321 with multivessel disease), 112 had additional angiography; of these 48 had 59 lesions suitable for analysis. Between infarct and noninfarct angiograms there was a significant change in minimal lumen diameter (1.53 +/- 0.51 mm vs. 1.78 +/- 0.65 mm, p < 0.001) and percentage stenosis (49.3 +/- 14.5% vs. 40.4 +/- 16.6%, p < 0.0001) of the nonculprit lesion without significant change in reference segment diameter, which was not predicted by changes in medication or hemodynamics. Twenty-one percent of patients had lesions >50% at AMI that were <50% at non-AMI angiography. Infarct versus noninfarct setting was the only significant independent predictor of change in nonculprit stenosis., Conclusions: Significant exaggeration of nonculprit lesion stenosis severity occurs at infarct angiography, which may affect revascularization decision making in an appreciable number of patients.

N(3,4-dimethoxycinnamoyl) anthranilic acid (tranilast) prevents the synchronous upregulation of isoforms and receptors of the transforming growth factor (TGF)-beta system after arterial injury and reduces restenosis after human coronary angioplasty. However, the effects of tranilast and the importance of the TGF-beta system in stent restenosis, in which inward remodeling is unimportant but inflammatory cell stimulation of neointima formation is exaggerated, are uncertain. Boston minipigs, treated with tranilast or vehicle, were subjected to endoluminal stenting, and the expression of TGF-beta1 and TGF-beta3, the expression of their signaling receptors ALK-5 and TbetaR-II, leukocyte numbers around the stent struts, and neointima development were assessed over 28 days. Stenting greatly increased early (5-day) mRNA expression of the 2 TGF-beta isoforms and their receptors. Immunohistochemical localization later showed that their concentrations were greatest in regions adjacent to stent struts, where leukocytes and collagen deposition were prevalent. Tranilast suppressed these elevations in TGF-beta mRNAs and reduced their immunoreactive peptides detectable around stent struts. The accumulation of leukocytes and deposition of collagen in these regions was also greatly inhibited by tranilast. These effects were associated with a 48% reduction in maximal neointimal cross-sectional area and 43% reduction in mean neointimal cross-sectional area at 28 days (P<0.05). We conclude that tranilast suppresses neointima development after stenting, effects that can be at least partly attributed to its ability to attenuate the induction of the TGF-beta system and leukocyte accumulation around stent struts.

The Calu-3 human cell line exhibits features of submucosal gland serous cells and secretes HCO(3)(-). The aim of this study was to identify the HCO(3)(-) transporters present in these cells by studying their role in the regulation of intracellular pH (pH(i)). Calu-3 cells were grown on coverslips, loaded with the pH-sensitive fluorescent dye BCECF, and their fluorescence intensity monitored as an indication of pH(i). Cells were acidified with NH(4)Cl (25 mM, 1 min) and pH(i) recovery recorded. In the absence of HCO(3)(-), initial recovery was 0.208 +/- 0.016 pH units min(-1) (n = 37). This was almost abolished by removal of extracellular Na(+) and by amiloride (1 mM), consistent with the activity of a Na(+)-H(+) exchanger (NHE). In the presence of HCO(3)(-) and CO(2), recovery (0.156 +/- 0.018 pH units min(-1)) was abolished (reduced by 91.8 +/- 6.7 %, n = 7) by removal of Na(+) but only attenuated (by 63.3 +/- 5.8 %, n = 9) by amiloride. 4,4-Dinitrostilbene-2,2-disulfonic acid (DNDS) inhibited recovery by 45.8 +/- 5.0 % (n = 7). The amiloride-insensitive recovery was insensitive to changes in membrane potential, as confirmed by direct microelectrode measurements, brought about by changing extracellular [K(+)] in the presence of either valinomycin or the K(+) channel opener 1-EBIO. In addition, forskolin (10 microM), which activates the cystic fibrosis transmembrane conductance regulator Cl(-) conductance in these cells and depolarises the cell membrane, had no effect on recovery. Removal of extracellular Cl(-) trebled pH(i) recovery rates, suggesting that an electroneutral, DNDS-sensitive, Cl(-)-HCO(3)(-) exchanger together with a NHE may be involved in pH(i) regulation and HCO(3)(-) secretion in these cells. RT-PCR detected the expression of the electrogenic Na(+)-HCO(3)(-) cotransporter NBC1 and the Cl(-)-HCO(3)(-) exchanger (AE2) but not the electroneutral Na(+)-HCO(3)(-) cotransporter NBCn1.

Vascular remodeling implies the concept of compensatory vessel enlargement to preserve luminal dimensions during atheromatous plaque development. However, negative remodeling, i.e. vessel shrinkage in response to plaque accumulation has also been described. So far, the factors influencing positive or negative remodeling are uncertain. We hypothesized that vascular distensibility, a measure of vessel compliance, is related to compensatory enlargement. In 58 patients undergoing intravascular ultrasound interrogation of a de novo lesion prior to coronary intervention, the cross-sectional vessel area (VA), lumen area (LA) and plaque area (PA = VA minus LA) were measured at end diastole and end systole at the lesion site and at the proximal and distal reference segments. Positive remodeling was defined to be present when the VA at the lesion was > 1.05 times larger than that at the proximal reference (group A), negative remodeling when the VA at the lesion was < 0.95 of the reference site (group C) and in-between was considered to be intermediate (group B). Vessel compliance was measured by calculating vascular distensibility. Results showed a similar LA at the lesion site in all groups (4.18+/-2.18 vs. 4.36+/-1.19 vs. 3.74+/-1.81 mm2, NS) while VA and PA were significantly larger in group A (17.19+/-5.08 vs. 14.22+/-3.66 and 12.45+/-4.82 mm2, p = 0.005 and 13+/-4.55 vs. 9.95+/-3.58 and 8.7+/-3.83, p = 0.003, respectively). Vascular distensibility at the proximal reference segment was significantly greater in group A (3.55+/-2.67 vs. 1.25+/-1.03 and 0.85+/-0.73 mmHg(-1), p < 0.001) with a positive correlation between remodeling and distensibility (R = 0.52, p < 0.001). In a multiple regression model including clinical and lesional factors, distensibility was the only predictor of remodeling. In conclusion, these results suggest that compensatory vessel enlargement occurs to a greater degree in patients with increased coronary artery distensibility, which appears to be a predictor for positive remodeling.

Background: Coronary artery angioplasty triggers healing that causes constrictive remodeling. Because collagen accumulation correlates with constrictive remodeling and aldosterone has been implicated in collagen accumulation, we examined how aldosterone and the mineralocorticoid receptor antagonists spironolactone and eplerenone affect remodeling and collagen in porcine coronary and iliac arteries after angioplasty., Methods and Results: Twenty-four pigs were allocated into 4 treatment groups: oral eplerenone (100 mg/d), oral spironolactone (200 mg/d), subcutaneous aldosterone (400 microgram/d), or no treatment. Twenty-eight days after angioplasty of the coronary arteries, eplerenone increased total vessel area by 30% (P<0.05) and luminal area by nearly 60% (P<0.05) compared with the no-treatment group, without affecting neointima size. These effects were accompanied by a 65% reduction in neointimal and medial collagen density (both P<0.05). Spironolactone was less effective, and aldosterone tended to exert opposite effects on coronary artery structure after angioplasty. These effects were not observed in angioplastied iliac arteries., Conclusions: Eplerenone attenuates constrictive remodeling after coronary artery angioplasty by mechanisms involving reduction in collagen accumulation, which thus appears to be an important contributor to constrictive remodeling of angioplastied coronary arteries.

Objectives: The study was done to elucidate the relationship between baseline arterial remodeling and clinical outcome following stenting., Background: The impact of preintervention arterial remodeling on subsequent vessel response and clinical outcome has been reported following nonstent coronary interventions. However, in stented segments, the impact of preintervention remodeling on clinical outcome has not been clarified., Methods: Preintervention remodeling was assessed in 108 native coronary lesions by using intravascular ultrasound (IVUS). Positive remodeling (PR) was defined as vessel area (VA) at the target lesion greater than that of average reference segments. Intermediate or negative remodeling (IR/NR) was defined as VA at the target lesion less than or equal to that of average reference segment. Remodeling index expressed as a continuous variable was defined as VA at the target lesion site divided by that of average reference segments., Results: Positive remodeling was present in 59 (55%) and IR/NR in 49 (45%) lesions. Although final minimal stent areas were similar (7.76 +/- 1.80 vs. 8.09 +/- 1.90 mm2, p = 0.36), target vessel revascularization (TVR) rate at nine-month follow-up was significantly higher in the PR group (22.0% vs. 4.1%, p = 0.01). By multivariate logistic regression analysis, higher remodeling index was the only independent predictor of TVR (p = 0.02)., Conclusions: Lesions with PR before intervention appear to have a worse clinical outcome following IVUS-guided stenting. Intravascular ultrasound imaging before stenting may be helpful to stratify lesions at high risk for accelerated intimal proliferation.

-The predominant cause of restenosis after angioplasty is now thought to be inward remodeling, but the mechanisms responsible are unknown. Remodeling in normal vessels is regulated by the endothelium in response to altered shear stress. Although the endothelium is often damaged by angioplasty, restenosis rates after angioplasty have been correlated with impaired coronary flow. Thus, we examined how increases or decreases in blood flow through balloon catheter-injured rat carotid arteries affect vessel morphometry (4, 10, and 28 days), cell migration (4 days), and levels of promigratory mRNAs (2 and 10 days). After 28 days, the luminal area in vessels with low blood flow was significantly less than in those with normal and high blood flow (0.17+/-0.01 [low] versus 0.24+/-0.06 [normal] versus 0.30+/-0.02 [high] mm(2), P:<0.01), predominantly because of accentuated inward remodeling (or reduced area within the external elastic lamina; 0.42+/-0.02 [low] versus 0.54+/-0.07 [normal] versus 0.53+/-0.04 [high] mm(2), P:<0.05). Low flow also enhanced smooth muscle cell migration 4 days after injury by 90% above normal and high flows (P:<0.01). Two days after injury, low flow significantly increased levels of mRNAs encoding promigratory peptides (integrin alpha(v)ss(3), transforming growth factor-ss(1), CD44v6, MDC9, urokinase plasminogen activator receptor, and ss-inducible gene h3); these changes persisted 10 days after injury and were localized to the neointima. Low blood flow may promote restenosis after angioplasty because of its adverse effect on vessel remodeling, and it is associated with the augmented expression of multiple genes central to cell migration and restenosis.

We found that after audit and physician-guided changes in our protocol, the door-to-inflation times for primary angioplasty/stenting were markedly reduced. Because our preaudit mean time was similar to the national average, this may have wide applicability.

Background: Many systemic, regional and lesion factors have been identified which may influence arterial remodeling, but little is known about the importance of extravascular resistance to vessel enlargement. As myocardial systolic splinting may significantly affect vessel expansion the effect of plaque orientation on arterial remodeling in eccentric coronary atherosclerotic lesions was examined., Methods: Using intravascular ultrasound imaging to obtain cross-sectional vessel area (VA), plaque area (PA) and lumen area (LA), remodeling in eccentric left anterior descending coronary artery lesions was compared which predominantly involved the pericardial or free arc (P, n=25) and the myocardial side (M, n=40) of the vessel wall. Normalized vessel area (NVA, VA(lesion)/VA(reference)) was compared as a continuous and categorical variable (positive>1.05, intermediate 0.95-1.05, negative<0.95) as well as remodeling index (RI, VA(lesion)-VA(reference)/PA(lesion)-PA(reference))., Results: The two groups were well matched for clinical and lesion characteristics known to affect remodeling. Reference segments areas were similar in the two groups; while lesion LA was also similar, in the pericardial group there was significantly greater lesion PA (P 12.78+/-0.72, M 10.26+/-0.50 mm(2), P<0.05) and VA (P 15.71+/-0.90, M 12.82+/-0.57 mm(2), P<0.05) demonstrating enhanced compensatory remodeling. Outward remodeling was significantly greater in P than in M by both NVA (P 1.03+/-0.03, M 0.86+/-0.03, P<0.01) and RI (P 0.02+/-0.07, M -1.10+/-0.32, P<0.01). Positive, intermediate and negative remodeling occurred in nine, nine and seven lesions in P and in four, ten and 26 lesions in M (P<0.01)., Conclusions: Remodeling compensates more for plaque growth in eccentric coronary lesions which are surrounded by the pericardium than those surrounded by the myocardium. Extravascular resistance appears to influence arterial remodeling.

Recent advances in the treatment of heart disease, in particular cardiovascular gene therapy and therapeutic angiogenesis, highlight the need for efficient and practical local delivery methods for the heart. We assessed the feasibility of percutaneous selective coronary venous cannulation and injection as a novel approach to local myocardial drug delivery. In anesthetized swine, the coronary sinus was cannulated percutaneously and a balloon-tipped catheter advanced to the anterior interventricular vein (AIV) or middle cardiac vein (MCV). During balloon occlusion, venous injection of radiographic contrast caused regional infiltration of targeted myocardial regions. Complete AIV occlusion had no impact on LAD flow parameters. Videodensitometric analysis following venous injection showed that radiographic contrast persisted for at least 30 min. Selective regional myocardial infiltration is feasible by this approach, targeting selected myocardial beds, including the apex, anterior wall, septum, and inferoposterior wall. This novel technique has potential application for local myocardial drug or growth factor delivery. Cathet. Cardiovasc. Intervent. 51:358-363, 2000., (Copyright 2000 Wiley-Liss, Inc.)

Relative contributions of remodelling and neointimal hyperplasia to restenosis after coronary angioplasty have been inferred from studies using iliofemoral arteries, despite differences in structure/function and smooth muscle cell lineage. We compared the response to balloon overstretch injury of coronary arteries (C, n = 16) and similar sized branches of the iliac arteries (I, n = 18) using preinjury vessel diameter (P). inflated balloon size in vivo (B) and the manufacturer predicted inflated size (M) to examine arterial compliance, as well as resulting injury and morphology in perfusion fixed vessels. Despite similar degrees of oversizing (M/P) in the coronary and iliac arteries (C, 1.44 +/- 0.04; I, 1.51 +/- 0.02), the compliance to overstretch (B-P/M-P) was significantly greater in the coronary than the iliac arteries (C, 0.71 +/- 0.05; I, 0.51 +/- 0.03) (P <0.05) and was associated with a higher injury score (C, 1.64 +/- 0.31; I, 0.39 +/- 0.18 P < 0.05)--only 5/18 iliac vessels had rupture of the IEL compared with 13/16 in the coronary bed. In a subgroup of animals whose vessels (C:n = 7; I:n = 8) were perfusion fixed 28 days after injury, coronary arteries had greater intimal area (C:1.03 +/- 0.42; I:0.10 +/- 0.03 mm2, P < 0.05) but larger luminal area (C:1.61 +/- 0.71; 1:0.76 +/- 0.51, P < 0.05) due to greater area within EEL (C:3.38 +/- 0.49;1:] .49 +/- 0.54, P < 0.05) or less inward remodelling. The injuries resulting from similar strategies of balloon overstretch in the coronary and the iliac arteries are different and affect healing responses--iliac arteries remodel more while coronary arteries develop more intimal hyperplasia. These results indicate that caution is warranted when extrapolating results from the iliac to the coronary artery when investigating restenosis after angioplasty.

Study Objective: A prospective, randomized controlled trial of new-onset atrial fibrillation was conducted to compare the efficacy and safety of sotalol and amiodarone (active treatment) with rate control by digoxin alone for successful reversion to sinus rhythm at 48 hours., Methods: We prospectively randomly assigned 120 patients with atrial fibrillation of less than 24 hours' duration to treatment with sotalol, amiodarone, or digoxin using a single intravenous dose followed by 48 hours of oral treatment. Patients had ECG monitoring for 48 hours, and time of reversion, adequacy of rate control, and numbers of adverse events were compared. After 48 hours, those still in atrial fibrillation underwent cardioversion according to a standardized protocol. After 48 hours of therapy and attempted cardioversion, the number of patients whose rhythms had successfully reverted were compared., Results: There was a significant reduction in the time to reversion with both sotalol (13. 0+/-2.5 hours, P <.01) and amiodarone (18.1+/-2.9 hours, P <.05) treatment compared with digoxin only (26.9+/-3.4 hours). By 48 hours, the active treatment group was significantly more likely to have reverted to sinus rhythm than the rate control group (95% versus 78%, P <.05; risk ratio 5.4, 95% confidence interval [CI] 1.5 to 19.2 ). In those patients whose rhythms did not revert to sinus rhythm, there was superior ventricular rate control in the sotalol group at both 24 and 48 hours compared with those who received either amiodarone or digoxin. There were also fewer adverse events in the active treatment group compared with the rate control group., Conclusion: Immediate pharmacologic therapy for new-onset atrial fibrillation with class III antiarrhythmic drugs (sotalol or amiodarone) improves complication-free 48-hour reversion rates compared with rate control with digoxin.

Background: Coronary remodeling plays a significant role in lumen loss in transplant allograft vasculopathy (TxCAD), but the determinants of remodeling are unknown. We assessed the relationship between remodeling and plaque topography, coronary compliance, and blood flow in TxCAD., Methods and Results: One artery in each of 27 transplant patients was investigated with simultaneous intravascular ultrasound and coronary flow measurements (basal and hyperemic by Doppler flow wire). At 4 to 8 different cross sections (mean 5.1+/-1. 2), plaque topography (concentric or eccentric) was determined, and total vessel area, lumen area, and intimal/medial area (IMA) were measured. Mean remodeling ratio (vessel area/IMA) in eccentric lesions (E, n=28) was significantly larger than that in concentric lesions (C, n=70) (E 5.87+/-0.93 versus C 3.58+/-0.62; P<0.001), despite similar IMA (E 3.89+/-0.68 versus C 3.90+/-0.41; P=NS) and distribution of imaged segments. Remodeling ratio was consistently larger in eccentric lesions in all 3 vessel segments when analyzed separately, and mean remodeling ratio for each artery was larger in vessels with predominantly eccentric lesions. Coronary compliance ([Delta lumen area/diastolic lumen area]/Delta mean arterial pressure x 10(3)) was also significantly greater in eccentric lesions versus concentric lesions (proximal 1.00+/-0.39 versus 0.22+/-0.04; mid 0.71+/-0.17 versus 0.21+/-0.10; distal 0.43+/-0.13 versus 0. 01+/-0.08; all P<0.01). Coronary flow reserve was also significantly higher in coronary arteries with primarily eccentric lesions (E 2. 49+/-0.64 versus C 1.87+/-0.28; P<0.01)., Conclusions: Vessel remodeling in transplant vasculopathy is significantly greater in eccentric lesions than in concentric lesions, possibly due to greater coronary compliance and resistive vessel function.

We used intravascular ultrasound to show that outward remodeling predominates in lesions responsible for acute myocardial infarction, whereas negative remodeling is far more prevalent in lesions responsible for chronic stable angina. The total cholesterol:high-density lipoprotein ratio was also strongly correlated with outward remodeling.

Although it has been postulated that atherosclerotic stenotic lesions cannot remodel in response to altered flow, evidence to support or refute this hypothesis has been elusive. In vitro models have shown that accelerated endothelial shear stress occurs on the upstream side of stenoses, while turbulent lower shear stress is seen on the downstream side. We therefore compared vascular remodeling at paired sites 2 mm upstream and 2 mm downstream of the site of minimal lumen area in 25 atherosclerotic lesions in 23 patients using intravascular ultrasound. Remodeling was compared by 2 methods: normalized vessel area (vessel area(lesion)/vessel(reference) and remodeling index (change in vessel area/change in plaque area from reference). Normalized vessel area was significantly greater upstream than downstream (1.21+/-0.06 vs. 1.12+/-0.09; p<0.05), despite similar plaque burden (8.84+/-0.81 vs. 8.42+/-0.85 mm2) resulting in larger lumen area (8.15+/-1.02 vs. 6.10+/-0.88 mm2; p<0.05). Remodeling index was also significantly higher upstream than downstream (0.67+/-0.20 vs. 0.12+/-0.24, respectively, p<0.05). Accentuation of remodeling on the upstream side was significantly correlated (r = 0.54, p = 0.01) with the mean degree of shear acceleration expected by stenosis severity. Impaired remodeling on the downstream side may partly explain stenosis propagation down a vessel.

Vascular remodeling represents a spectrum of structural changes whereby the vascular wall responds to changes in its hemodynamic environment. Such changes may be classified as vessel enlargement (outward remodeling), diminution (inward remodeling), alternatively as adaptive (compensatory, appropriate to the hemodynamic stimulus), or maladaptive (dysfunctional, inappropriate). The direction and scale of remodeling are coordinated by endothelial production of growth factors, proteases, and cellular adhesion molecules in response to sensed changes in blood flow. In early atherosclerosis, outward remodeling preserves lumen size. Although protective in the long-term, the matrix degradation involved in this process may predispose atherosclerotic plaques to rupture, hence increasing the risks of acute coronary syndromes. Inward remodeling also occurs in advanced atherosclerotic lesions, whereby the vessel shrinks rather than enlarging, exacerbating rather than ameliorating stenosis. In transplant coronary artery disease, early inward remodeling may be a more important component of vessel stenosis than intimal thickening, while inappropriate inward remodeling appears to be as least as important as excessive intimal growth in the development of restenosis after angioplasty. Increased awareness of vascular remodeling, and in particular its malaptive forms, may provide new therapeutic insights for the future.

Tranilast (N(3,4-dimethoxycinnamoyl)anthranilic acid), an agent which in cell culture inhibits transforming growth factor-beta (TGF-beta) secretion and antagonises the effects of TGF-beta and platelet-derived growth factor (PDGF) on cell migration and proliferation, has been reported to reduce the incidence of restenosis after angioplasty in angiographically validated human clinical trials. We investigated in a rat model of balloon angioplasty whether tranilast's effects in vivo could be attributed to inhibition of expression of TGF-beta and/or its receptor types. Using a standardised reverse transcriptase-polymerase chain reaction (RT-PCR) assay, we examined the effects of three doses of tranilast (25, 50 and 100 mg/kg) on the expression of two TGF-beta isoforms, the types I and II TGF-beta receptors and two putative TGF-beta responses, induction of integrins alpha(v) and beta3 mRNA, 2 h after oral administration and 26 h after vessel injury. Tranilast attenuated in a dose-dependent and reversible manner the injury-induced increases in mRNA levels encoding TGF-beta1, TGF-beta3, two type I TGF-beta receptors ALK-5 and ALK-2, and the type II receptor TbetaRII. At the highest dose mRNA levels encoding TGF-beta1 and TbetaRII were attenuated to levels approaching or below those observed in uninjured vessels. Messenger RNAs encoding TGF-beta3, ALK-5 and ALK-2 were all attenuated by between 70 and 74% (all P < 0.05). Tranilast also attenuated in a reversible manner the elevations in mRNA levels for integrins alpha(v) and beta3 observed after vessel injury, by 90 and 72%, respectively. We also investigated, in cultured smooth muscle cells derived from injured carotid arteries, the extent to which tranilast (300 mg/l) attenuated any increases in expression of type I and type II receptors stimulated by PDGF-BB and TGF-beta1, growth factors implicated in smooth muscle cell migration and proliferation in injured vessels. Increases in mRNA levels of the type I receptors ALK-5 and ALK-2 induced by PDGF-BB and TGF-beta1 were almost completely prevented by tranilast. Tranilast also prevented the PDGF-BB induced increases in TbetaRII but only partially inhibited the TGF-beta1 induced upregulation of TbetaRII. We conclude that tranilast can inhibit transcriptional mechanisms associated with the upregulation of TGF-beta and its receptor types in balloon catheter injured vessels. It is possible that these mechanisms contribute to its ability to reduce the frequency of restenosis after angioplasty.

Recent evidence indicates that the type II transforming growth factor-beta (TGF-beta) receptor (TbetaRII) is a serine-threonine-tyrosine kinase. However, the significance of its tyrosine kinase is unclear. We investigated in vascular smooth muscle cells the effects of tyrosine kinase inhibition on the expression of TGF-beta receptor types I (ALK-5) and II (TbetaRII) mRNA, induced by TGF-beta1. TGF-beta1 elevated ALK-5 mRNA levels 5-fold; essentially similar TGF-beta1-dependent elevations were observed with growth factors, PDGF-BB and FGF-2. The tyrosine kinase inhibitor genistein abolished these TGF-beta1 and growth factor responses. TGF-beta1 also elevated TbetaRII mRNA levels which were not inhibited by genistein. We conclude that tyrosine kinases participate in defining how cells respond to TGF-beta.

Reye's syndrome (RS) is a biphasic illness that occurs predominately in children and adolescents. A prodromal viral illness (frequently influenza A or B or chicken pox) is followed by protracted vomiting and neurologic changes that start 3 to 5 days later, just when the child seems to be recovering. Aspirin has been identified as one factor contributing to the metabolic disorder that occurs. Since 1986 the FDA has required labels on all aspirin products warning about the association of aspirin use and RS. Media messages heightened public awareness regarding the alternatives to aspirin for analgesia and antipyretic use. Since 1988, the incidence of RS has decreased dramatically. RS is now more prevalent in older adolescents who may self-medicate. Because early recognition of the disease is associated with decreased morbidity and mortality, it is important for health care providers to recognize the symptoms of RS. Unexpected vomiting and disturbed brain functioning following a viral illness are symptoms of RS in children and adolescents. In infants, the symptoms of RS may be more subtle, including diarrhea, respiratory disturbances, and seizures.

Transforming growth factor-beta 1 (TGF-beta 1) has been implicated in neointima formation in mechanically injured vessels and in restenosis after angioplasty. To further understand the significance of TGF-beta s in neointima formation, we examined the temporal expression of three TGF-beta isoforms (-beta 1, -beta 2, and -beta 3), their receptors (ALK-2, ALK-5, and T beta RII), and two putative TGF-beta responses (elevations in alpha v and beta 3 integrin mRNAs) in balloon catheter-injured rat carotid arteries and their dependency on tyrosine kinase activity. Using a standardized reverse transcriptase-polymerase chain reaction assay optimized to estimate mRNA levels, we observed distinct patterns of mRNA regulation for TGF-beta 1, -beta 2, and -beta 3 during the 48 hours immediately after injury, which were localized to the vessel's media. TGF-beta 1 mRNA increased 10-fold during this time while TGF-beta 3 mRNA also increased almost 2-fold. There were also increases in mRNAs encoding the TGF-beta type I receptors ALK-5 and ALK-2, as well as the type II receptor (T beta RII). Eight hours after the injury, mRNA levels for ALK-2 and ALK-5 were on average 2-fold higher; mRNA encoding the type II receptor increased approximately 3-fold by 24 hours. There were also associated increases in TGF-beta 1, TGF-beta 3, ALK-5, and T beta RII immunoreactive peptide levels. Peak increases in mRNAs for integrins alpha v and beta 3 averaged approximately 2-fold and 2.5-fold, respectively. Perivascular administration of the tyrosine kinase inhibitor genistein at the time of vessel injury markedly (> 85%) inhibited elevations in mRNAs encoding TGF-beta 1, TGF-beta 3, T beta RII, and the two integrins alpha v and beta 3, while application of its inactive chemically similar homologue daidzein did not prevent the injury-induced elevations in mRNA levels. Since the increases in integrins alpha v and beta 3 mRNA could be theoretically attributed to TGF-beta actions despite being dependent on tyrosine kinase activity, we examined whether the observed elevations in integrins alpha v and beta 3 were due to TGF-beta 1 secretion, using cultured rat carotid artery smooth muscle cells. TGF-beta 1 neutralizing antibodies specifically inhibited elevations in integrins alpha v and beta 3 mRNAs due to platelet-derived growth factor-BB and fibroblast growth factor-2. We conclude that multiple components of the TGF-beta system in vessels are activated following injury and influence expression of integrin receptors important for smooth muscle cell migration. Activation of the TGF-beta system appears to be highly dependent on tyrosine kinases.

The patient described in this report had an apical radiolucency in the incisor region of the mandible. This had a similar appearance to an extensive periapical granuloma; misdiagnosis might easily have been made, especially since there had been a history of previous trauma to the region. The incisors were found to be vital and, in view of their poor prognosis, were removed with the lesion. The histological report showed it to be periapical cemental dysplasia.

We wished to examine the effects of diabetes on muscle glutamine kinetics. Accordingly, female Wistar rats (200 g) were made diabetic by a single injection of streptozotocin (85 mg/kg) and studied 4 days later; control rats received saline. In diabetic rats, glutamine concentration of gastrocnemius muscle was 33% less than in control rats: 2.60 +/- 0.06 mumol/g vs. 3.84 +/- 0.13 mumol/g (P < 0.001). In gastrocnemius muscle, glutamine synthetase activity (Vmax) was unaltered by diabetes (approx. 235 nmol/min per g) but glutaminase Vmax increased from 146 +/- 29 to 401 +/- 94 nmol/min per g; substrate Km values of neither enzyme were affected by diabetes. Net glutamine efflux (A-V concentration difference x blood flow) from hindlimbs of diabetic rats in vivo was greater than control values (-30.0 +/- 3.2 vs. -1.9 +/- 2.6 nmol/min per g (P < 0.001)) and hindlimb NH3 uptake was concomitantly greater (about 27 nmol/min per g). The glutamine transport capacity (Vmax) of the Na-dependent System Nm in perfused hindlimb muscle was 29% lower in diabetic rats than in controls (820 +/- 50 vs. 1160 +/- 80 nmol/min per g (P < 0.01)), but transporter Km was the same in both groups (9.2 +/- 0.5 mM). The difference between inward and net glutamine fluxes indicated that glutamine efflux in perfused hindlimbs was stimulated in diabetes at physiological perfusate glutamine (0.5 mM); ammonia (1 mM in perfusate) had little effect on net glutamine flux in control and diabetic muscles. Intramuscular Na+ was 26% greater in diabetic (13.2 mumol/g) than control muscle, but muscle K+ (100 mumol/g) was similar. The accelerated rate of glutamine release from skeletal muscle and the lower muscle free glutamine concentration observed in diabetes may result from a combination of: (i), a diminished Na+ electrochemical gradient (i.e., the net driving force for glutamine accrual in muscle falls); (ii), a faster turnover of glutamine in muscle and (iii), an increased Vmax/Km for sarcolemmal glutamine efflux.

This report reviews a young patient who had undergone orthodontic therapy leaving occlusal interferences which were initially able to be tolerated. When symptoms of dysfunction arose, the general practitioner referred her to a specialist. The treatment involved a segmental bite-plane. Symptoms returned when the patient was under stress, and a Michigan splint was made as the segmental type of bite-plane is unsuitable for long-term use.

In order to detect and characterise Na(+)-H+ countertransport in the fetal lung epithelium we have studied under a variety of conditions the effect of an outward facing H+ gradient on Na+ uptake into purified apical membrane vesicles prepared from alveolar type II cells. Kinetic analysis of the data reveals both a diffusional and a saturable component of total Na+ uptake. Evidence for the presence of a Na(+)-H+ exchanger is demonstrated by (1) stimulation of Na+ uptake by proton loading of vesicles both in the presence and absence of chemical voltage clamping; (2) saturation kinetics with respect to external Na+ with a Km of 16 mM and a Vmax of 2.1 nmol/mg protein per min; (3) amiloride inhibition of Na+ uptake driven by pH gradient. We conclude that although diffusion may be the major component of total Na+ uptake at physiological external Na+ concentration, Na(+)-H+ countertransport provides a possible mechanism for the acidification of fetal lung liquid in-vivo in addition to its established role in intracellular pH and volume regulation.

Rat skeletal muscle glutamine fell by 40% from 4.18 to 2.5 mumols/g wet weight (P less than 0.01) after 4 days of denervation. Over the same period net glutamine efflux from denervated hindlimbs [i.e., arteriovenous (a-v) concentration differences x blood flow] increased 3.5-fold (from -6.72 +/- 1.73 to -26 +/- 4.81 nmol.min-1.g-1, P less than 0.001). Gastrocnemius glutamine synthetase activity fell 48% after denervation (from 475 +/- 81 to 248 +/- 39 nmol.min-1.g-1, P less than 0.001), but glutaminase activity was not significantly altered (17 nmol.min-1.g-1). The maximal activity (Vmax) of the unidirectional Na(+)-dependent glutamine transporter (system Nm) was depressed by 45% from 1,020 +/- 104 to 571 +/- 9 nmol.min-1.g-1 (P less than 0.01), but the concentration at which transport was half maximal (Km) was not significantly altered (control 8.1 +/- 0.6 mM; denervated 6.52 +/- 0.12). Hindlimb denervation resulted in an increase of intramuscular Na+ by 17% and a fall of K+ by 12%, and the resting membrane potential in isolated muscles decreased from -75 +/- 10 to -59.5 +/- 5.5 mV. Membrane potential of perfused denervated muscle, isolated after acute addition of the Na+ channel blocker tetrodotoxin (TTX, 3 microM), repolarized to -66.4 +/- 3.2 mV. In perfused denervated preparations TTX caused an acute recovery of Vmax of unidirectional glutamine transport to 848 +/- 75 nmol.min-1.g-1; Km was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

1. The ionic permeabilities of the apical and basolateral membranes of sheep tracheal epithelial cells have been evaluated by studying the effect of ion replacements on the apical (Va) and basolateral (Vb) membrane potentials and apical voltage divider ratio (fa). 2. The results provide evidence for the existence of conductances for Cl-, Na+ and K+ at the apical membrane, and of an important K+ conductance at the basolateral membrane. These characteristics agree with the model for Cl- secretion and Na+ absorption proposed for tracheal epithelium of other species. 3. The short-circuit current (Isc) across this tissue was found to increase significantly when HCO3- and CO2 were added to the bathing solutions. The addition of 0.5 mM-SITS (4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid) to the serosal bathing solution decreased Isc only if HCO3- and CO2 were present in the bathing solutions. These results suggest the existence of a HCO3- secretion in sheep tracheal epithelium under short-circuit conditions. 4. The results obtained in HCO3- replacement studies are compatible with an electrically silent HCO3- entry across the basolateral membrane and an electrogenic exit at the apical membrane of the cells.

Anti-nitrate-reductase (NR) immunoglobulin-G (IgG) fragments inhibited nitrate uptake into Chlorella cells but had no affect on nitrite uptake. Intact anti-NR serum and preimmune IgG fragments had no affect on nitrate uptake. Membrane-associated NR was detected in plasma-membrane (PM) fractions isolated by aqueous two-phase partitioning. The PM-associated NR was not removed by sonicating PM vesicles in 500 mM NaCl and 1 mM ethylenediaminetetraacetic acid and represented up to 0.8% of the total Chlorella NR activity. The PM NR was solubilized by Triton X-100 and inactivated by Chlorella NR antiserum. Plasma-membrane NR was present in ammonium-grown Chlorella cells that completely lacked soluble NR activity. The subunit sizes of the PM and soluble NRs were 60 and 95 kDa, respectively, as determined by sodium-dodecyl-sulfate electrophoresis and western blotting.

1. Anodal break action potentials were found to be a feature of denervated rat skeletal muscle fibres.2. Depolarized innervated fibres failed to respond to anodal break stimulation in the same way as denervated fibres.3. The critical level for action potential generation is related to membrane polarization in denervated fibres but not in innervated fibres. This relationship is inhibited by the I.P. administration of actinomycin D, which also prevents the onset of anodal break action potentials in 3-day denervated fibres.

Membrane associated nitrate reductase (NR) was detected in plasma membrane (PM) fractions isolated by aqueous two-phase partitioning from barley (Hordeum vulgare L. var CM 72) roots. The PM associated NR was not removed by washing vesicles with 500 millimolar NaCl and 1 millimolar EDTA and represented up to 4% of the total root NR activity. PM associated NR was stimulated up to 20-fold by Triton X-100 whereas soluble NR was only increased 1.7-fold. The latency was a function of the solubilization of NR from the membrane. NR, solubilized from the PM fraction by Triton X-100 was inactivated by antiserum to Chlorella sorokiniana NR. Anti-NR immunoglobulin G fragments purified from the anti-NR serum inhibited NO3- uptake by more than 90% but had no effect on NO2- uptake. The inhibitory effect was only partially reversible; uptake recovered to 50% of the control after thorough rinsing of roots. Preimmune serum immunoglobulin G fragments inhibited NO3- uptake 36% but the effect was completely reversible by rinsing. Intact NR antiserum had no effect on NO3- uptake. The results present the possibility that NO3- uptake and NO3- reduction in the PM of barley roots may be related.

The nature of the injury and recovery of nitrate uptake (net uptake) from NaCl stress in young barley (Hordeum vulgare L, var CM 72) seedlings was investigated. Nitrate uptake was inhibited rapidly by NaCl, within 1 minute after exposure to 200 millimolar NaCl. The duration of exposure to saline conditions determined the time of recovery of NO3- uptake from NaCl stress. Recovery was dependent on the presence of NO3- and was inhibited by cycloheximide, 6-methylpurine, and cerulenin, respective inhibitors of protein, RNA, and sterol/fatty acid synthesis. These inhibitors also prevented the induction of the NO3- uptake system in uninduced seedlings. Uninduced seedlings exhibited endogenous NO3- transport activity that appeared to be constitutive. This constitutive activity was also inhibited by NaCl. Recovery of constitutive NO3- uptake did not require the presence of NO3-.

The effect of salinity stress on metabolic heat output of barley (Hordeum vulgare L.) root tips was measured by isothermal microcalorimetry. Several varieties differing in tolerance to salinity were compared and differences quantified. Two levels of inhibition by increasing salt were found. Following the transition from the initial rate of the first level, inhibition remained at about 50% with further increases in salt concentration up to 150 millimolar. The concentration of salt required to inhibit to this level was cultivar dependent. At highter concentrations (>150 millimolar) of salt, metabolism was further decreased. This decrease was not cultivar dependent. The decreased rate of metabolic heat output at the first transition could be correlated with decreases in uptake of NO3-, NH4+, and Pi that occurred as the salt concentration was increased. The high degree of dependence of the inhibition of metabolic heat output on NaCl concentration points to a highly cooperative reaction responsible for the general inhibition of metabolism and nutrient uptake. The time required to attain the first level of salt inhibition is less than 20 minutes. Inhibition of root tips was not reversible by washing with salt free solutions. In addition to revealing these features of salt inhibition, isothermal microcalorimetry is a promising method for convenient and rapid determination of varietal differences in response to increasing salinity.

The effect of Ca2+ on NO3- assimilation in young barley (Hordeum vulgare L. var CM 72) seedlings in the presence and absence of NaCl was studied. Calcium increased the activity of the NO3- transporter under saline conditions, but had little effect under nonsaline conditions. Calcium decreased the induction period for the NO3- transporter under both saline and nonsaline conditions but had little effect on its apparent Km for NO3- both in the presence and absence of NaCl. The enhancement of NO3- transport by Ca2+ under saline conditions was dependent on the presence of Ca2+ in the uptake solution along with the salt, since Ca2+ had no effect when supplied before or after salinity stress. Although Mn2+ and Mg2+ enhanced NO3- uptake under saline conditions, neither was as effective as Ca2+. In longer studies, increasing the Ca2+ concentration in saline nutrient solutions resulted in increases in NO3- assimilation and seedling growth.