Tubular system volume changes in twitch fibres from toad and rat skeletal muscle assessed by confocal microscopy

The volume of the extracellular compartment (tubular system) within intact muscle fibres from cane toad and rat was measured under various conditions using confocal microscopy. Under physiological conditions at rest, the fractional volume of the tubular system (t-sys(Vol)) was 1.38 +/- 0.09% (n = 17),1.41 +/- 0.09% (n = 12) and 0.83 +/- 0.07% (n = 12) of the total fibre volume in the twitch fibres from toad iliofibularis muscle, rat extensor digitorum longus muscle and rat soleus muscle, respectively. In toad muscle fibres, the t-sys(Vol) decreased by 30% when the tubular system was fully depolarized and decreased by 15% when membrane cholesterol was depleted from the tubular system with methyl-beta-cyclodextrin but did not change as the sarcomere length was changed from 1.93 to 3.30 mum. There was also an increase by 30% and a decrease by 25% in t-sys(Vol) when toad fibres were equilibrated in solutions that were 2.5-fold hypertonic and 50% hypotonic, respectively. When the changes in total fibre volume were taken into consideration, the t-sys(Vol) expressed as a percentage of the isotonic fibre volume did actually decrease as tonicity increased, revealing that the tubular system in intact fibres cannot be compressed below 0.9% of the isotonic fibre volume. The results can be explained in terms of forces acting at the level of the tubular wall. These observations have important physiological implications showing that the tubular system is a dynamic membrane structure capable of changing its volume in response to the membrane potential, cholesterol depletion and osmotic stress but not when the sarcomere length is changed in resting muscle.

Biochemical and structural characterization of a beta-1,3-1,4-glucanase from Bacillus subtilis 168

beta-1,3-1,4-Glucanases (E.C. 3.2.1.73) hydrolyze linked beta-D-glucans, such as lichenan and barley beta-glucan. Recombinant beta-1,3-1,4-glucanase from Bacillus subtilis expressed in Escherichia coil and purified by Ni-NTA chromatography exhibited optimum activity at 50 degrees C and pH 6.0. The catalytic half-life at 60 degrees C decreased from 90 to 5 min when the enzyme was incubated in the presence and absence of Ca(2+) respectively. The kinetic parameters of lichenan hydrolysis were 2695, 3.1 and 1220 for V(max) (mu mol/min/mg), K(m) (mg mL(-1)) and K(cat) (s(-1)), respectively. Analysis by DLS, AUC and SAXS demonstrated the enzyme is monomeric in solution. Chemical denaturation monitored by ITFE and far-UV CD yielded Delta G(H2O) values of 9.6 and 9.1 kcal/mol, respectively, showing that the enzyme has intermediate stability when compared with other Bacillus beta-1,3-1,4-glucanases. The crystal structure shows the anti-parallel jelly-roll beta-sheet conserved in all GH16 beta-1,3-1,4-glucanases, with the amino acid differences between Bacillus sp. enzymes that are likely determinants of stability being distributed throughout the protein. (C) 2011 Elsevier Ltd. All rights reserved.

Treatment of Coronary Artery Disease in Hemodialysis Patients Evaluated for Transplant-A Registry Study

Background. We assessed the results of a noninvasive therapeutic strategy on the long-term occurrence of cardiac events and death in a registry of patients with chronic kidney disease (CKD) and coronary artery disease (CAD). Methods. We analyzed 519 patients with CKD (56+/-9 years, 67% men, 67% whites) on maintenance hemodialysis with clinical or scintigraphic evidence of CAD by using coronary angiography. Results. In 230 (44%) patients, coronary angiography revealed significant CAD (lumen reduction >= 70%). Subjects with significant CAD were kept on medical treatment (MT; n=184) or referred for myocardial revascularization (percutaneous transluminal coronary angioplasty/coronary artery bypass graft-intervention; n=30) according to American College of Cardiology/American Heart Association guidelines. In addition, 16 subjects refused intervention and were also followed-up. Event-free survival for patients on MT at 12, 36, and 60 months was 86%, 71%, and 57%, whereas overall survival was 89%, 71%, and 50% in the same period, respectively. Patients who refused intervention had a significantly worse prognosis compared with those who actually underwent intervention (events: hazard ratio=4.50; % confidence interval=1.48-15.10; death: hazard ratio=3.39; % confidence interval 1.41-8.45). Conclusions. In patients with CKD and significant CAD, MT promotes adequate long-term event-free survival. However, failure to perform a coronary intervention when necessary results in an accentuated increased risk of events and death.

Glu298Asp eNOS gene polymorphism causes attenuation in nonexercising muscle vasodilatation

Dias RG, Alves MJ, Pereira AC, Rondon MU, dos Santos MR, Krieger JE, Krieger MH, Negrao CE. Glu298Asp eNOS gene polymorphism causes attenuation in nonexercising muscle vasodilatation. Physiol Genomics 37: 99-107, 2009. First published January 21, 2009; doi:10.1152/physiolgenomics.90368.2008.-The influence of Glu298Asp endothelial nitric oxide synthase (eNOS) polymorphism in exercise-induced reflex muscle vasodilatation is unknown. We hypothesized that nonexercising forearm blood flow (FBF) responses during handgrip isometric exercise would be attenuated in individuals carrying the Asp298 allele. In addition, these responses would be mediated by reduced eNOS function and NO-mediated vasodilatation or sympathetic vasoconstriction. From 287 volunteers previously genotyped, we selected 33 healthy individuals to represent three genotypes: Glu/Glu [n = 15, age 43 +/- 3 yr, body mass index (BMI) 22.9 +/- 0.3 kg/m(2)], Glu/Asp (n = 9, age 41 +/- 3 yr, BMI 23.7 +/- 1.0 kg/m(2)), and Asp/Asp (n = 9, age 40 +/- 4 yr, BMI 23.5 +/- 0.9 kg/m(2)). Heart rate (HR), mean blood pressure (MBP), and FBF (plethysmography) were recorded for 3 min at baseline and 3 min during isometric handgrip exercise. Baseline HR, MBP, FBF, and forearm vascular conductance (FVC) were similar among genotypes. FVC responses to exercise were significantly lower in Asp/Asp when compared with Glu/Asp and Glu/Glu (Delta = 0.07 +/- 0.14 vs. 0.64 +/- 0.20 and 0.57 +/- 0.09 units, respectively; P = 0.002). Further studies showed that intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA) did not change FVC responses to exercise in Asp/Asp, but significantly reduced FVC in Glu/Glu (Delta = 0.79 +/- 0.14 vs. 0.14 +/- 0.09 units). Thus the differences between Glu/Glu and Asp/Asp were no longer observed (P = 0.62). L-NMMA + phentolamine increased similarly FVC responses to exercise in Glu/Glu and Asp/Asp (P = 0.43). MBP and muscle sympathetic nerve activity increased significant and similarly throughout experimental protocols in Glu/Glu and Asp/Asp. Individuals who are homozygous for the Asp298 allele of the eNOS enzyme have attenuated nonexercising muscle vasodilatation in response to exercise. This genotype difference is due to reduced eNOS function and NO-mediated vasodilatation, but not sympathetic vasoconstriction.

Colorectal cancer in familial adenomatous polyposis: Are there clinical predictive factors?

Background: Familial Adenomatous Polyposis (FAP) is a hereditary disorder with multiple colorectal polyps that exhibit an almost inevitable risk of colorectal cancer (CRC) in untreated patients. Goals: To evaluate clinical features related to CRC risk at diagnosis. Material and methods: Charts from 88 patients were reviewed to collect information regarding age, family history, symptoms, polyposis severity and association with CRC. Results: 41 men (46.6%) and 47 women (53.4%) were assisted. CRC was detected in 53 patients (60.2%), with a frequency of 9.1% under 20 years, 58% between 21-40 and 85% over 41 years of age. Average age of patients without CRC was lower at treatment (29.5 vs. 40.0 years; p=0.001). Family history was reported by 58 patients (65.9%), whose average age did not differ from those who didn`t report it (33.4 vs. 34.4; p=0.17). Asymptomatic patients comprised 10.2% of the total; in this group, CRC incidence was much lower when compared to those presenting symptoms (1.1% vs. 65.8%; p=0.001). Patients without CRC presented a shorter length of symptoms (15.2 vs. 26.4 months; p=0.03) and less frequent weight loss (11.4% vs. 33.9%; p=0.01). At colonoscopy, polyposis was classified as attenuated in 12 patients (14.3%), who presented greater average age (48.2 vs. 33.3 years; p=0.02) and equal CRC incidence (58.3% vs. 58.3%; p=0.6) when compared to those with classic polyposis. Conclusions: The risk of CRC in FAP patients 1) increases significantly after the second decade; 2) is associated with higher age, weight loss, presence and duration of simptomatology; 3) is similar in patients with attenuated or classic phenotype. (C) 2010 AEC. Published by Elsevier Espana, S.L. All rights reserved.

Customized Topography-guided Photorefractive Keratectomy With the MEL-70 Platform and Mitomycin C to Correct Hyperopia After Radial Keratotomy

PURPOSE: To evaluate topography-guided photorefractive keratectomy (PRK) for correcting hyperopia and astigmatism after radial keratotomy (RK). METHODS., Prospective study of 12 consecutive patients (19 eyes) who were treated with topography-guided PRK with 0.02% mitomycin C using an Asclepion-Meditec MEL-70 excimer laser with a 9.5-mm ablation zone. All eyes were operated by the same surgeon and followed for 1 year. RESULTS: Thirteen eyes had complete epithelialization by day 7 and all eyes by day 10. At 1 year, uncorrected visual acuity was 20/25 or better in 42.1% of eyes and 20/40 or better in 68.4%. Preoperative mean spherical equivalent refraction was +3.80 +/- 2.47 diopters (D) and +0.24 +/- 2.36 D (P <.001) 1 year postoperative, with 47.4% of eyes being within +/- 1.00 D and 73.7% within +/- 2.00 D. Preoperative mean cylinder was -2.30 +/- 1.41 D and -0.62 +/- 0.73 D (P <.1001) 1 year postoperative. At 1 year, 68.4% of eyes gained at least 1 line of best-spectacle corrected visual acuity, 36.8% gained more than 1 line, and only 2 eyes lost 1 line (one due to corneal haze). Three eyes developed central haze. Mean regression from 6 to 12 months in these 3 eyes was +1.83 D and in the remaining 16 eyes was -0.50 D. CONCLUSIONS: Topography-guided PRK with mitomycin C was safe and reasonably effective for the treatment of hyperopia after RK [J Refract Surg. 2008;24:911-922.]

Effects of estradiol and norethisterone on lipids, insulin resistance and carotid flow

Objectives: To evaluate the lipid profile, insulin resistance and vasomotricity, and the interaction between these factors, in postmenopausal women receiving hormone therapy. Methods: A prospective, randomized, double-blind study was carried out in which 77 postmenopausal women received one of the three treatment regimens: (A) 2 mg oral micronized estradiol (E(2)) (n = 25); (B) 2 mg oral E(2) + 1 mg oral norethisterone acetate (NETA) (n = 28); or Q placebo (n = 24), daily for 6 months. Evaluations were carried out at baseline and at the end of treatment on lipid and lipoprotein profiles, homeostasis model assessment of insulin resistance (HOMA-IR) and pulsatility index (PI) of the internal carotid artery by Doppler ultrasonography. Results: Mean increases of 15.6% and 2.4% and a reduction of 6.4% in high-density lipoprotein (HDL) levels were found for the E(2), E(2) + NETA and placebo groups, respectively. Reductions of 9.5% and 3.7% and an increase of 12.1% in low-density lipoprotein (LDL), and reductions of 20.0% and 3.8% and an increase of 28.8% in the LDL:HDL ratio were found for the E(2), E(2) + NETA and placebo groups, respectively (p < 0.001 in all cases). Insulin levels and HOMA-IR decreased 12.8% and 12.3% in the E2 group and increased 12.9% and 16.0% in the E(2) + NETA group (p < 0.05), respectively. Carotid PI following treatment was 1.18 +/- 0.23, 1.38 +/- 0.20 and 1.41 +/- 0.21 for the E(2), E(2) + NETA and placebo groups, respectively (p = 0.0006). Conclusions: Oral estrogen therapy led to an improvement in lipid profile, insulin resistance and carotid blood flow, which was cancelled when NETA was associated. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Morphology of the subgenual prefrontal cortex in pediatric bipolar disorder

Objectives The subgenual prefrontal cortex (SGPFC) is an important brain region involved in emotional regulation and reward mechanisms Volumetric abnormalities in this region have been identified in adults with bipolar disorder but thus far not in pediatric cases We examined the volume of this brain region in subjects with pediatric bipolar disorder (PBD) and compared them to healthy controls Methods Fifty one children and adolescents (mean age +/- SD 13 2 +/- 2 9 y) with DSM-IV PBD and 41 (mean age +/- SD 13 7 +/- 2 7 y) healthy comparison subjects (HC) underwent 1 5 T structural magnetic resonance imaging (MRI) brain scans We traced the SGPFC manually and compared SGPFC gray matter volumes using analysis of covariance with age gender and intracranial volume as covariates We also examined the relationship of family history of affective disorders and medication status to SGPFC volumes Results SGPFC volumes were not significantly different in PBD and HC subjects However exploratory analysis showed PBD subjects who had one or more first degree relatives with mood disorders (n = 33) had significantly smaller left hemisphere SGPFC compared to HC (p = 003 Sidak corrected) Current usage of a mood stabilizer was significantly associated with larger right SGPFC volume in PBD (F = 4 82 df = 1/41 p = 0 03) Conclusion Subjects with PBD and a close family history of mood disorders may have smaller left SGPFC volumes than HC Mood stabilizing medication may also impact SGPFC size and could have masked more subtle abnormalities overall (C) 2010 Elsevier Ltd All rights reserved

Prednisone monotherapy induced remission in a group of patients with membranous lupus nephritis

The treatment of membranous lupus nephritis (MLN) is still controversial in the literature. We conducted a retrospective analysis of patients in two medical centers of Sao Paulo-Brazil in order to evaluate the clinical response in patients submitted to either a regimen with prednisone alone or to a double immunosuppressive regimen (prednisone plus cyclophosphamide or prednisone plus azathioprine). Methods: MLN female patients were enrolled in this retrospective study conducted from February 1999 to June 2007. Data were collected from the patients` medical charts. Race distribution was similar in both groups: Caucasian (72.3%) and Afro-Latin-American (27.7%). The prednisone regimen consisted of 1 mg/kg/day for 8 weeks and tapering until 0.1 mg/kg/day (n = 29). The double immunosuppressive treatment consisted of the same doses of prednisone plus monthly intravenous cyclophosphamide or azathioprine for 6 months (n = 24). Criteria for remission (complete and partial) and renal function loss as well as flare criteria followed those used in the literature. Results: There was no difference between the prednisone group and the double immunosuppressive group regarding age (33.2 +/- 9.4 vs. 29.1 +/- 9.1 y), estimated GFR (76.5 +/- 26.6 vs. 74.1 +/- 39.6 ml/min/1.73 m(2)), serum albumin (2.8 +/- 0.7 vs. 2.6 +/- 0.3 g/dl), positive ANA (87.5 vs. 90.0%), positive anti-dsDNA (47.6 vs. 44.0%), renal SLEDAI indices (6.6 +/- 2.6 vs. 7.0 +/- 3.1), follow-up time (71 +/- 46 vs. 62 +/- 45 months), as well as proteinuria (3.1 +/- 1.9 vs. 4.8 +/- 2.4 g/day) and number of non-nephrotic patients (6 in the prednisone group vs. 3 in the double immunosuppressive group). The prednisone group presented higher C3 values (85.2 +/- 31.5 vs. 62.3 +/- 41.6 U/ml, p = 0.04). Clinical and laboratory characteristics at 6 months and at last follow-up did not reveal any differences between treatment regimens. Renal survival after an 8-year follow-up did not differ in both groups (prednisone group 86.2% vs. double immunosuppressive group 75%), and patients in both groups showed a high rate of renal flares (prednisone group 51.7% vs. double immunosuppressive group 62.5%). Univariate analysis showed that only patient age predicted flares (r = -0.048, p = 0.04). Borderline significance was obtained for proteinuria analysis (p = 0.07). Adverse effects did not differ between the groups. Conclusions: A regimen of corticosteroids in MLN induced a high remission rate after 6 months. Both treatment regimens showed a high flare rate and age was the only predictive parameter (r = -0.048, p = 0.04). Renal survival after 8 years did not differ between the groups.

Topical interleukin-1 receptor antagonist inhibits inflammatory cell infiltration into the cornea

Interleukin (IL)-1 alpha and beta are important modulators of many functions of corneal epithelial and stromal cells that occur following injury to the cornea, including the influx of bone marrow-derived inflammatory cells into the stroma attracted by chemokines released from the stroma and epithelium. In this study, we examined the effect of topical soluble IL-1 receptor antagonist on bone marrow-derived cell influx following corneal epithelial scrape injury in a mouse model. C57BL/6 mice underwent corneal epithelial scrape followed by application of IL-1 receptor antagonist (Amgen, Thousand Oaks, CA) at a concentration of 20 mg/ml or vehicle for 24 h prior to immunocytochemical detection of marker CD11b-positive cells into the stroma. In two experiments, topical IL-1 receptor antagonist had a marked effect in blocking cell influx. For example, in experiment 1, topical IL-1 receptor antagonist markedly reduced detectible CD11b-positive cells into the corneal stroma at 24 It after epithelial injury compared with the vehicle control (3.5 +/- 0.5 (standard error of the mean) cells/400x field and 13.9 +/- 1.2 cells/400x field, respectively, p < 0.01). A second experiment with a different observer performing cell counting had the same result. Thus, the data demonstrate conclusively that topical IL-1 receptor antagonist markedly down-regulates CD-11b-positive monocytic cell appearance in the corneal stroma. Topical IL-1 receptor antagonist could be an effective adjuvant for clinical treatment of corneal conditions in which unwanted inflammation has a role in the pathophysiology of the disorder. (c) 2008 Elsevier Ltd. All rights reserved.

Immunohistochemical study of GLUT-1 in oral peripheral nerve sheath tumors

AIM: To investigate the immunoexpression and diagnostic applicability of human erythrocyte-type glucose transporter protein (GLUT-1) in oral peripheral nerve sheath tumors. MATERIAL AND METHODS: Specimens diagnosed as oral peripheral nerve sheath tumors archived in the Oral Pathology Service of Universidade Federal de Minas Gerais from 1966 to 2006 were evaluated. Thirty-four lesions were included: 15 traumatic neuromas, 11 neurofibromas, four neurilemmomas, and four malignant peripheral nerve sheath tumors (MPNST). One case of neurofibroma was associated with neurofibromatosis type I. Immunohistochemistry for S-100 and GLUT-1 was performed. S-100 was immunopositive in all lesions. RESULTS: Benign lesions were immunopositive for GLUT-1 except in two (18.2%) cases of neurofibromas. In the traumatic neuroma, the perineuriums were immunopositive for GLUT-1. In the neurofibroma, the immunoreactivity was heterogeneous. Immunopositivity was observed at levels of 54.5% in the periphery of the lesion, 9.1% in the center, and 18.2% in both. The neurilemmoma demonstrated immunopositivity in the capsule. One case (25%) of MPNST presented GLUT-1 positive stain in occasional cells distributed homogeneously in all the tumor area. CONCLUSION: GLUT-1 is a useful marker for perineurial cells and should be included in the oral peripheral nerve sheath tumors immunophenotyping thus aiding in the correct diagnosis of these lesions.

Morphometric evaluation of the repair of critical-size defects using demineralized bovine bone and autogenous bone grafts in rat calvaria

Objective: To evaluate the repair of critical-size bone defects in rats treated with demineralized bovine bone (DBB) compared with autogenous bone (AB). Material and method: A bone defect of 8 mm in diameter was created in the calvaria of 50 Rattus norvegicus, treated either with DBB or AB. Sub-groups of five rats of each group were killed at 7, 14, 21, 30 and 90 days post-operatively, and the skulls were removed and processed histologically. Histological sections were stained with hematoxylin and eosin. Result: Histological analysis showed complete closure of the defects with new bone at 90 days in group AB, and substitution of the biomaterial by fibrotic connective tissue in the DBB group at 21 days. Morphometric analysis showed that DBB was rapidly absorbed at 14 days, with its volume density decreasing from 47%+/- 0.8% at 7 days to 1.2%+/- 0.41% at 14 days. Subsequently, volume densities of the connective tissue and neoformed bone increased from 51.1%+/- 11.17% to 86.8%+/- 7.92% and from 1.9%+/- 1.13% to 12%+/- 8.02%, respectively, for the same time interval. The volume density of AB particles did not change throughout the experimental periods, but the amount of new bone increased markedly between 7 and 90 days, from 4.5%+/- 1.57% to 53.5%+/- 6.42% (P < 0.05). Conclusion: DBB did not provide complete repair of the defects, with significantly less new bone formation than in the AB group.

Effects of Ethanol on the Surface and Bulk Properties of a Microwave-Processed PMMA Denture Base Resin

Purpose: This study evaluated the effect of different concentrations of ethanol on hardness, roughness, flexural strength, and color stability of a denture base material using a microwave-processed acrylic resin as a model system. Materials and Methods: Sixty circular (14 x 4 mm) and 60 rectangular microwave-polymerized acrylic resin specimens (65 x 10 x 3 mm(3)) were employed in this study. The sample was divided into six groups according to the ethanol concentrations used in the immersion solution, as follows: 0% (water), 4.5%, 10%, 19%, 42%, and 100%. The specimens remained immersed for 30 days at 37 degrees C. The hardness test was performed by a hardness tester equipped with a Vickers diamond penetrator, and a surface roughness tester was used to measure the surface roughness of the specimens. Flexural strength testing was carried out on a universal testing machine. Color alterations (Delta E) were measured by a portable spectrophotometer after 12 and 30 days. Variables were analyzed by ANOVA/Tukey`s test (alpha = 0.05). Results: For the range of ethanol-water solutions for immersion (water only, 4.5%, 10%, 19.5%, 42%, and 100%), the following results were obtained for hardness (13.9 +/- 2.0, 12.1 +/- 0.7, 12.9 +/- 0.9, 11.2 +/- 1.5, 5.7 +/- 0.3, 2.7 +/- 0.5 VHN), roughness (0.13 +/- 0.01, 0.15 +/- 0.07, 0.13 +/- 0.05, 0.13 +/- 0.02, 0.23 +/- 0.05, 0.41 +/- 0.19 mu m), flexural strength (90 +/- 12, 103 +/- 18, 107 +/- 16, 90 +/- 25, 86 +/- 22, 8 +/- 2 MPa), and color (0.8 +/- 0.6, 0.8 +/- 0.3, 0.7 +/- 0.4, 0.9 +/- 0.3, 1.3 +/- 0.3, 3.9 +/- 1.5 Delta E) after 30 days. Conclusions: The findings of this study showed that the ethanol concentrations of tested drinks affect the physical properties of the investigated acrylic resin. An obvious plasticizing effect was found, which could lead to a lower in vivo durability associated with alcohol consumption.

Selenium content of Australian foods: A review of literature values

The aim of this study was to review the published literature values for the selenium content of Australian foods. A secondary aim was to compare the results for Australian foods with food composition data from international sources to investigate the extent of geographical variation. Published food composition data sources for the selenium content in Australian foods were identified and assessed for data quality using established criteria. The selenium content is available for 148 individual food items. The highest values found are for fish (12.0-63.2 mug/100 g), meats (4.75-37.9 mug/100 g) and eggs (9.00-41.4 mug/100 g), followed by cereals (1.00-20.3 mug/100 g). Moderate levels are seen in dairy products (2.00-7.89 mug/100 g) while most fruits and vegetables have low levels (trace-3.27 mug/100 g). High selenium foods show the greatest level of geographical variation, with foods from the United States generally having higher selenium levels than Australian foods and foods from the United Kingdom and New Zealand having lower levels. This is the first attempt to review the available literature for selenium composition of Australian foods. These data serve as an interim measure for the assessment of selenium intake for use in epidemiological studies of diet-disease relationships. (C) 2002 Published by Elsevier Science Ltd.

Patients with early diabetic heart disease demonstrate a normal myocardial response to dobutamine

OBJECTIVES We sought to use quantitative markers of the regional left ventricular (LV) response to stress to infer whether diabetic cardiomyopathy is associated with ischemia. BACKGROUND Diabetic cardiomyopathy has been identified in clinical and experimental studies, but its cause remains unclear. METHODS We studied 41 diabetic patients with normal resting LV function and a normal dobutamine echo and 41 control subjects with a low probability of coronary disease. Peak myocardial systolic velocity (Sm) and early diastolic velocity (Em) in each segment were averaged, and mean Sm and Em were compared between diabetic patients and controls and among different stages of dobutamine stress. RESULTS Both Sm and Em progressively increased from rest to peak dobutamine stress. In the diabetic group, Sm was significantly lower than in control subjects at baseline (4.2 +/- 0.9 cm/s vs. 4.7 +/- 0.9 cm/s, p = 0.012). However, Sin at a low dose (6.0 +/- 1.3), before peak (8.4 +/- 1.8), and at peak stress (8.9 +/- 1.8) in diabetic patients was not significantly different from that of controls (6.3 +/- 1.4, 8.9 +/- 1.6, and 9.6 +/- 2.1 cm/s, respectively). The Em (cm/s) in the diabetic group (rest: 4.2 +/- 1.2; low dose: 5.0 +/- 1.4; pre-peak: 5.3 +/- 1.1; peak: 5.9 +/- 1.5) was significantly lower than that of controls (rest: 5.8 +/- 1.5; low dose: 6.6 +/- 1.5; pre-peak: 6.9 +/- 1.3; peak: 7.3 +/- 1.7; all p < 0.001). However, the absolute and relative increases in Sm or Em from rest to peak stress were similar in diabetic and control groups. CONCLUSIONS Subtle LV dysfunction is present in diabetic patients without overt cardiac disease. The normal response to stress suggests that ischemia due to small-vessel disease may not be important in early diabetic heart muscle disease. (C) 2003 by the American College of Cardiology Foundation.