Preoperative Hypoalbuminemia Predicts Early Mortality Following Open Abdominal Surgery in Patients Above 60 Years of Age.

BACKGROUND: Major abdominal surgery in older and frail patients is associated with considerable morbidity and mortality. Plasma albumin is routinely measured in the clinic and has been proposed as an indicator of frailty. This study aimed to investigate if plasma albumin is a predictor of mortality in older patients undergoing open abdominal surgery. MATERIALS AND METHODS: We conducted a single-center, register-based retrospective study of patients, aged ⩾60 years who underwent one of 81 open abdominal surgical procedures. Patients operated on during the period from January 1st, 2000 to May 31st, 2013 were consecutively identified in the Danish National Patient Registry. Plasma albumin was measured within 30 days prior to surgery and the primary endpoint was 30-day postoperative mortality. RESULTS: 3,639 patients were included of whom 68.2% underwent emergency surgery. The rate of severe hypoalbuminemia (plasma albumin < 28 g/L) was 43.4%. Preoperative plasma albumin was lower in patients with a fatal 30-day outcome (mean 20.6 g/L vs 30.1 g/L in survivors, p < 0.0001). Other independent predictive parameters of 30-day mortality were age, male sex, and emergency surgery. We present an algorithm including these four variables for the prediction of 30-day mortality for patients aged ⩾60 years undergoing open abdominal surgery. CONCLUSION: Preoperative plasma albumin is a predictor of 30-day mortality in patients above 60 years of age following open abdominal surgery. Assessment of plasma albumin in conjunction with other risk factors such as age, sex, and surgical priority may improve preoperative decision-making.

Siglec expression on the surface of human, bull and ram sperm.

Sialic acid (Sia) is a major constituent of both the sperm glycocalyx and female reproductive mucosal surface and is involved in regulating sperm migration, uterotubal reservoir formation and oocyte binding. Siglecs (sialic acid-binding immunoglobulin - like lectins) commonly found on immune cells, bind to Sia in a linkage- and sugar-specific manner and often mediate cell-to-cell interactions and signalling. Proteomic and transcriptomic analysis of human and bovine sperm have listed Siglecs, but to date, their presence and/or localisation on sperm has not been studied. Therefore, the aim of this study was to characterise the presence of Siglecs on the surface of bovine, human and ovine sperm using both immunostaining and Western blotting. Siglec 1, 2, 5, 6, 10 and 14 were identified and displayed both species- and regional-specific expression on sperm. Almost universal expression across Siglecs and species was evident in the sperm neck and midpiece region while variable expression among Siglecs, similar among species, was detected in the head and tail regions of the sperm. The possible role for these proteins on sperm is discussed.

No increased sperm DNA fragmentation index in semen containing human papillomavirus or herpesvirus.

It remains unknown whether human papillomaviruses (HPVs) or human herpesviruses (HHVs) in semen affect sperm DNA integrity. We investigated whether the presence of these viruses in semen was associated with an elevated sperm DNA fragmentation index. Semen from 76 sperm donors was examined by a PCR-based hybridization array that identifies all HHVs and 35 of the most common HPVs. Sperm DNA integrity was determined by the sperm chromatin structure assay. HPVs or HHVs, or both, were found in 57% of semen samples; however, sperm DNA fragmentation index was not increased in semen containing these viruses.

The effect of discontinued use of antimicrobial growth promoters on the risk of therapeutic antibiotic treatment in Danish farrow-to-finish pig farms.

This study estimated the effect of discontinued use of antimicrobial growth promoters (duAGPs) on the risk of antibiotic treatment for diarrhoea, arthritis, pneumonia, unthriving and miscellaneous disorders in Danish pig farms. The estimation was done in a case-crossover study comparing: (1) the proportion of days per farm where treatment was performed (PDT) and (2) the proportion of pigs treated per day per farm at days where treatment was performed (PPT) before and after duAGPs at 68 farrow-to-finish farms. The farms were selected using a two-stage (veterinarian/farm) convenience sampling. On average, during the first year after duAGPs there was a significant increase in the risk of antibiotic treatment for diarrhoea (PDT: OR 2.5, 95% CI 1.7-3.8; PPT: OR 1.6, 95% CI 1.1-2.2). However, the effect varied among farms--some farms experienced substantial problems, while others experienced few problems after duAGPs. No effect was identified for the risk of treatment for other diseases.

Intubation conditions after rocuronium or succinylcholine for rapid sequence induction with alfentanil and propofol in the emergency patient.

BACKGROUND AND OBJECTIVE: Previous studies mainly conducted on elective patients recommend doses of 0.9-1.2 mg kg[-1] rocuronium to obtain comparable intubation conditions with succinylcholine 1.0 mg kg[-1] after 60 s during a rapid-sequence induction. We decided to compare the overall intubating conditions of standard doses of rocuronium 0.6 mg kg[-1] and succinylcholine 1.0 mg kg[-1] during a strict rapid-sequence induction regimen including propofol and alfentanil. METHODS: Male and female patients (ASA I-III) older than 17 yr scheduled for emergency abdominal or gynaecological surgery and with increased risk of pulmonary aspiration of gastric content were randomized to a rapid-sequence induction with succinylcholine 1.0 mg kg[-1] or rocuronium 0.6 mg kg[-1]. Patients with a predicted difficult airway were excluded. A senior anaesthesiologist 'blinded' for the randomization performed the intubation 60 s after injection of the neuromuscular blocker. Intubating conditions were evaluated according to an established guideline. Tracheal intubation not completed within 30 s was recorded as failed. RESULTS: 222 patients were randomized. Three patients had their operation cancelled and 10 did not fulfil the inclusion criteria. Clinically acceptable intubation conditions were present in 93.5% and 96.1% of patients in the succinylcholine group (n=107) and the rocuronium group (n=102), respectively (P=0.59). CONCLUSIONS: During a rapid-sequence induction with alfentanil and propofol, both rocuronium 0.6 mg kg[-1] and succinylcholine 1.0 mg kg[-1] provide clinically acceptable intubation conditions in 60 s in patients scheduled for emergency surgery. Under the conditions of this rapid-sequence induction regimen rocuronium may be a substitute for succinylcholine.

Acceleromyography of the orbicularis oculi muscle I: significance of the electrode position.

BACKGROUND: This study aimed to establish the best position of the stimulating electrodes for facial nerve stimulation during acceleromyographic monitoring from the orbital part of the orbicularis oculi muscle. METHODS: In 59 anaesthetised patients, an acceleration transducer was positioned over the middle of the eyebrow. In 47 patients, supramaximal train-of-four (TOF) stimulation was established for four electrode pairs with different positions along the facial nerve and behind the ear. The electrode pair with the lowest, the intermediate, and the highest supramaximal stimulating current based on first response (T1) in TOF was found in each patient. A possible response from direct muscle stimulation was evaluated during complete vecuronium block. In 12 patients, supramaximal stimulation was established using a stimulation sequence different from the one used in the first part of the study. RESULTS: The best positions for the stimulating electrodes were either with both electrodes just lateral to the eye, or with one electrode lateral to the eye and one in front of the ear. In most patients, supramaximal stimulation was obtained at these positions at 20-60 mA. However, in 10-21% of the patients, supramaximal stimulation could not be obtained. During complete block, 1-4 responses with a twitch height of 3-11% were recorded in 80% of the patients. CONCLUSION: The best placements of the stimulation electrodes are either just lateral to the eye or along the zygomatic arch. However, supramaximal stimulation may often not be obtainable, and activation of other facial muscles may be a confounding factor that may impede correct evaluation of the degree of neuromuscular block.

Acceleromyography of the orbicularis oculi muscle II: comparing the orbicularis oculi and adductor pollicis muscles.

BACKGROUND: The orbicularis oculi (OO) muscle has been recommended for neuromuscular monitoring when the adductor pollicis (AP) muscle is not available. We investigated whether neuromuscular block could be measured reliably from the orbital part of the OO muscle by the use of acceleromyography. METHODS: During propofol, fentanyl, and alfentanil anaesthesia two TOF-Guards (Organon Teknika NV, Boxtel, the Netherlands) with acceleration transducers placed on the distal phalanx of the thumb and over the middle of the eyebrow, respectively, were used to measure neuromuscular block simultaneously in 23 patients during vecuronium-induced and neostigmine-antagonized neuromuscular block. For both muscles, the simultaneously recorded first response (T1) in the train-of-four (TOF) and TOF-ratio were measured both during onset and recovery of the block. Furthermore, both the AP muscle T1 and TOF-ratio responses were plotted against 10% intervals of the OO muscle responses during onset and recovery, respectively. RESULTS: The orbicularis oculi muscle had a shorter latency and a faster recovery to TOF-ratio 0.80 compared with the AP muscle. During onset and recovery, pronounced variations of the AP muscle T1 and TOF-ratio responses were observed when compared with the OO muscle. CONCLUSION: A significant clinical disagreement exists between the degree of paralysis measured at the OO and the AP muscles. It is impossible to obtain a reasonable estimate of the degree of block at the AP muscle when the block is measured from the OO muscle with acceleromyography. If used, there is substantial risk of overlooking a residual block, and adequate recovery of the block should be confirmed by a final AP muscle measurement.

Polybrominated diphenyl ethers: occurrence, dietary exposure, and toxicology.

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in plastics (concentration, 5--30%) and in textile coatings. Commercial products consist predominantly of penta-, octa-, and decabromodiphenyl ether mixtures, and global PBDE production is about 40,000 tons per year. PBDEs are bioaccumulated and biomagnified in the environment, and comparatively high levels are often found in aquatic biotopes from different parts of the world. During the mid-1970--1980s there was a substantial increase in the PBDE levels with time in both sediments and aquatic biota, whereas the latest Swedish data (pike and guillemot egg) may indicate that levels are at steady state or are decreasing. However, exponentially increasing PBDE levels have been observed in mother's milk during 1972--1997. Based on levels in food from 1999, the dietary intake of PBDE in Sweden has been estimated to be 0.05 microg per day. Characteristic end points of animal toxicity are hepatotoxicity, embryotoxicity, and thyroid effects as well as maternal toxicity during gestation. Recently, behavioral effects have been observed in mice on administration of PBDEs during a critical period after birth. Based on the critical effects reported in available studies, we consider the lowest-observed-adverse-effect level (LOAEL) value of the PBDE group to be 1 mg/kg/day (primarily based on effects of pentaBDEs). In conclusion, with the scientific knowledge of today and based on Nordic intake data, the possible consumer health risk from PBDEs appears limited, as a factor of over 10(6) separates the estimated present mean dietary intake from the suggested LOAEL value. However, the presence of many and important data gaps, including those in carcinogenicity, reproduction, and developmental toxicity, as well as additional routes of exposure, make this conclusion only preliminary. Moreover, the time trend of PBDEs in human breast milk is alarming for the future.

The Arabidopsis eer1 mutant has enhanced ethylene responses in the hypocotyl and stem.

By screening for enhanced ethylene-response (eer) mutants in Arabidopsis, we isolated a novel recessive mutant, eer1, which displays increased ethylene sensitivity in the hypocotyl and stem. Dark-grown eer1 seedlings have short and thick hypocotyls even in the absence of added ethylene. This phenotype is suppressed, however, by the ethylene biosynthesis inhibitor 1-aminoethoxyvinyl-glycine. Following ethylene treatment, the dark-grown eer1 hypocotyl response is greatly exaggerated in comparison with the wild type, indicating that the eer1 phenotype is not simply due to ethylene overproduction. eer1 seedlings have significantly elevated levels of basic-chitinase expression, suggesting that eer1 may be highly sensitive to low levels of endogenous ethylene. Adult eer1 plants display exaggerated ethylene-dependent stem thickening, which is an ethylene response previously unreported in Arabidopsis. eer1 also has enhanced responsiveness to the ethylene agonists propylene and 2,5-norbornadiene. The eer1 phenotype is completely suppressed by the ethylene-insensitive mutation etr1-1, and is additive with the constitutive ethylene-response mutation ctr1-3. Our findings suggest that the wild-type EER1 product acts to oppose ethylene responses in the hypocotyl and stem.

The molecular physiology of heavy metal transport in the Zn/Cd hyperaccumulator Thlaspi caerulescens.

An integrated molecular and physiological investigation of the fundamental mechanisms of heavy metal accumulation was conducted in Thlaspi caerulescens, a Zn/Cd-hyperaccumulating plant species. A heavy metal transporter cDNA, ZNT1, was cloned from T. caerulescens through functional complementation in yeast and was shown to mediate high-affinity Zn(2+) uptake as well as low-affinity Cd(2+) uptake. It was found that this transporter is expressed at very high levels in roots and shoots of the hyperaccumulator. A study of ZNT1 expression and high-affinity Zn(2+) uptake in roots of T. caerulescens and in a related nonaccumulator, Thlaspi arvense, showed that alteration in the regulation of ZNT1 gene expression by plant Zn status results in the overexpression of this transporter and in increased Zn influx in roots of the hyperaccumulating Thlaspi species. These findings yield insights into the molecular regulation and control of plant heavy metal and micronutrient accumulation and homeostasis, as well as provide information that will contribute to the advancement of phytoremediation by the future engineering of plants with improved heavy metal uptake and tolerance.

Effect of aluminum on cytoplasmic Ca2+ homeostasis in root hairs of Arabidopsis thaliana (L.).

Aluminum inhibition of root growth is a major world agricultural problem where the cause of toxicity has been linked to changes in cellular calcium homeostasis. Therefore, the effect of aluminum ions (Al) on changes in cytoplasmic free calcium concentration ([Ca2+]c) was followed in root hairs of wild-type, Al-sensitive and Al-resistant mutants of Arabidopsis thaliana (L.) Heynh. Generally, Al exposure resulted in prolonged elevations in tip-localized [Ca2+]c in both wild-type and Al-sensitive root hairs. However, these Al-induced increases in [Ca2+]c were not tightly correlated with growth inhibition, occurring up to 15 min after Al had induced growth to stop. Also, in 32% of root hairs examined growth stopped without a detectable change in [Ca2+]c. In contrast, Al-resistant mutants showed little growth inhibition in response to AlCl3 exposure and in no case was a change in [Ca2+]c observed. Of the other externally applied stresses tested (oxidative and mechanical stress), both were found to inhibit root hair growth, but only oxidative stress (H2O2, 10 microM) caused a prolonged rise in [Ca2+]c similar to that induced by Al. Again this increase occurred after growth had been inhibited. The lack of a tight correlation between Al exposure, growth inhibition and altered [Ca2+]c dynamics suggests that although exposure of root hairs to toxic levels of Al causes an alteration in cellular Ca2+ homeostasis, this may not be a required event for Al toxicity. The elevation in [Ca2+]c induced by Al also strongly suggests that the phytotoxic action of Al in root hairs is not through blockage of Ca2(+)-permeable channels required for Ca2+ influx into the cytoplasm.

Association of the Arabidopsis CTR1 Raf-like kinase with the ETR1 and ERS ethylene receptors.

In Arabidopsis thaliana, signal transduction of the hormone ethylene involves at least two receptors, ETR1 and ERS, both of which are members of the two-component histidine protein kinase family that is prevalent in prokaryotes. The pathway also contains a negative regulator of ethylene responses, CTR1, which closely resembles members of the Raf protein kinase family. CTR1 is thought to act at or downstream of ETR1 and ERS based on double mutant analysis; however, the signaling mechanisms leading from ethylene perception to the regulation of CTR1 are unknown. By using the yeast two-hybrid assay, we detected a specific interaction between the CTR1 amino-terminal domain and the predicted histidine kinase domain of ETR1 and ERS. We subsequently verified these interactions by using an in vitro protein association assay(s). In addition, we determined that the amino-terminal domain of CTR1 can associate with the predicted receiver domain of ETR1 in vitro. Based on deletion analysis, the portion of CTR1 that interacts with ETR1 roughly aligns with the regulatory region of Raf kinases. These physical associations support the genetic evidence that CTR1 acts in the pathway of ETR1 and ERS and suggest that these interactions could be involved in the regulation of CTR1 activity.

Aluminum-resistant Arabidopsis mutants that exhibit altered patterns of aluminum accumulation and organic acid release from roots.

Al-resistant (alr) mutants of Arabidopsis thaliana were isolated and characterized to gain a better understanding of the genetic and physiological mechanisms of Al resistance. alr mutants were identified on the basis of enhanced root growth in the presence of levels of Al that strongly inhibited root growth in wild-type seedlings. Genetic analysis of the alr mutants showed that Al resistance was semidominant, and chromosome mapping of the mutants with microsatellite and random amplified polymorphic DNA markers indicated that the mutants mapped to two sites in the Arabidopsis genome: one locus on chromosome 1 (alr-108, alr-128, alr-131, and alr-139) and another on chromosome 4 (alr-104). Al accumulation in roots of mutant seedlings was studied by staining with the fluorescent Al-indicator dye morin and quantified via inductively coupled argon plasma mass spectrometry. It was found that the alr mutants accumulated lower levels of Al in the root tips compared with wild type. The possibility that the mutants released Al-chelating organic acids was examined. The mutants that mapped together on chromosome 1 released greater amounts of citrate or malate (as well as pyruvate) compared with wild type, suggesting that Al exclusion from roots of these alr mutants results from enhanced organic acid exudation. Roots of alr-104, on the other hand, did not exhibit increased release of malate or citrate, but did alkalinize the rhizosphere to a greater extent than wild-type roots. A detailed examination of Al resistance in this mutant is described in an accompanying paper (J. Degenhardt, P.B. Larsen, S.H. Howell, L. V. Kochian [1998] Plant Physiol 117: 19-27).

Aluminum resistance in the Arabidopsis mutant alr-104 is caused by an aluminum-induced increase in rhizosphere pH.

A mechanism that confers increased Al resistance in the Arabidopsis thaliana mutant alr-104 was investigated. A modified vibrating microelectrode system was used to measure H+ fluxes generated along the surface of small Arabidopsis roots. In the absence of Al, no differences in root H+ fluxes between wild type and alr-104 were detected. However, Al exposure induced a 2-fold increase in net H+ influx in alr-104 localized to the root tip. The increased flux raised the root surface pH of alr-104 by 0.15 unit. A root growth assay was used to assess the Al resistance of alr-104 and wild type in a strongly pH-buffered nutrient solution. Increasing the nutrient solution pH from 4.4 to 4.5 significantly increased Al resistance in wild type, which is consistent with the idea that the increased net H+ influx can account for greater Al resistance in alr-104. Differences in Al resistance between wild type and alr-104 disappeared when roots were grown in pH-buffered medium, suggesting that Al resistance in alr-104 is mediated only by pH changes in the rhizosphere. This mutant provides the first evidence, to our knowledge, for an Al-resistance mechanism based on an Al-induced increase in root surface pH.

Al Inhibits Both Shoot Development and Root Growth in als3, an Al-Sensitive Arabidopsis Mutant.

In als3, an Al-sensitive Arabidopsis mutant, shoot development and root growth are sensitive to Al. Mutant als3 seedlings grown in an Al-containing medium exhibit severely inhibited leaf expansion and root growth. In the presence of Al, unexpanded leaves accumulate callose, an indicator of Al damage in roots. The possibility that the inhibition of shoot development in als3 is due to the hyperaccumulation of Al in this tissue was examined. However, it was found that the levels of Al that accumulated in shoots of als3 are not different from the wild type. The inhibition of shoot development in als3 is not a consequence of nonspecific damage to roots, because other metals (e.g. LaCl3 or CuSO4) that strongly inhibit root growth did not block shoot development in als3 seedlings. Al did not block leaf development in excised als3 shoots grown in an Al-containing medium, demonstrating that the Al-induced damage in als3 shoots was dependent on the presence of roots. This suggests that Al inhibition of als3 shoot development may be a delocalized response to Al-induced stresses in roots following Al exposure.

Effects of compression bandaging on leg pulsatile blood flow.

Leg external compression bandaging is the mainstay of venous ulcer treatment, yet little is known about the impact of therapeutic compression levels on arterial haemodynamics. In this study, the effect of foot-to-knee, four-layer compression bandaging on below-knee arterial pulsatile blood flow was assessed by nuclear magnetic resonance flowmetry. In 14 healthy supine subjects bilateral flow measurements at five below-knee sites without compression, and after compressing one leg to an average malleolar sub-bandage pressure of 40.7 +/- 4.0 mmHg, revealed a potentially important new phenomenon. The forefoot-to-knee compression bandaging caused a highly significant (P < 0.001) increase in the bandaged leg pulsatile blood flow owing to increases in both peak flow and pulse width. It is hypothesized that arteriolar vasodilatation, induced either myogenically by reduced transmural pressure or by vasodilatory substance release triggered by increased venous shear stress, produce the observed compression-related phenomenon. Whatever the mechanism(s), the finding of a compression-associated pulsatile flow increase suggests a previously undiscovered arterial linkage, which may play a role in the well-documented beneficial effects of compression bandaging in venous ulcer treatment. A possible impact of the arterial flow-pulse increase is speculated to effect venous ulcer outcome via a decrease in leucocyte effects in the distal microvasculature, as a consequence of the more vigorous haemodynamic state.

The effect of succinylcholine on atracurium-induced neuromuscular block.

BACKGROUND: The interaction between prior succinylcholine and atracurium has been found only after full recovery of succinylcholine block. We investigated whether the effect of succinylcholine on atracurium block may depend on the level of recovery from succinylcholine. METHODS: Fifty patients in 4 groups received atracurium 0.2 mg/kg when first response (T1) in train-of-four (TOF) after succinylcholine 1 mg/kg had recovered to 5%, 25%, 75% or 100%. A control group received only atracurium. The following indices were compared: the time from injection of atracurium to maximum block (onset time) and to return of T1 to 25% (duration 25%), maximal depression of T1, time from 25% to 75% recovery of T1 (interval 25-75%) and time from injection of atracurium to a TOF ratio of 0.75 (duration TOF 0.75). RESULTS: Onset time was shorter, max T1 depression was greater and duration 25% increased the more succinylcholine recovery progressed. Neither interval 25-75% nor duration TOF 0.75 varied with the level of recovery from succinylcholine. The control group showed a shorter latency and onset time compared to the early (5%) recovery group and a longer onset time and less depressed T1 compared to the late (100%) recovery group. There was no difference between the control group and the early or late recovery groups, respectively for duration 25% or duration TOF 0.75. CONCLUSION: The effect of prior administration of succinylcholine on atracurium block depends on the state of recovery from succinylcholine and concerns both its potency, onset and duration characteristics.

Pulsatile blood flow asymmetry in paired human legs.

Average leg blood flow has been extensively measured using non-invasive methods, but knowledge concerning pulsatile flow at specific leg cross-sections in normal or vascularly impaired limbs is quite limited. The present study used nuclear magnetic resonance flowmetry to address two fundamental questions; (1) to what extent are pulsatile flow differences present between paired-legs? and (2) is paired-leg flow symmetry affected by the presence of lower extremity arterial disease (LEAD)? Comparisons of left-right leg pulsatile blood flow (ml/min), perfusion (ml/min/100cc), and arterial status index at multiple leg sites showed highly significant correlations between legs (P < 0.001) in 57 normal and 37 patients with LEAD. To evaluate symmetry, the ratio of lower to higher paired-leg flow parameter values at five below-knee sites were averaged. Results showed all ratios significantly greater in normal subjects (P < 0.001). These findings establish the distribution and range of leg flow symmetry in vascularly normal individuals and show significant symmetry reductions accompanying bilateral LEAD. Although the cause of the asymmetry is presently unknown, non-uniform disease progression between paired legs may be involved. These initial findings provide a basis for subsequent research regarding the possible use of bilateral flow asymmetry assessment to further clarify the pathophysiological progression process and the possibility of using symmetry-based parameters to develop early markers of sub-clinical peripheral arterial disease progression.

Functional microcirculatory impairment: a possible source of reduced skin oxygen tension in human diabetes mellitus.

Lower extremity transcutaneous oxygen tension (TcPO2) is used in diagnostic and prognostic indicator of tissue perfusion and is reduced in diabetes mellitus. Since cardiac output, leg blood flow and microvascular perfusion each can singly or jointly effect tissue oxygenation, the relative importance of macro- vs microvascular factors has not been resolved. To clarify this issue we compared TcPO2 levels in diabetic and nondiabetic subjects in whom cardiac output, leg pulsatile blood flow, and microcirculatory perfusion parameters were noninvasively measured. In 60 diabetic and 60 nondiabetic subjects the following measurements were done on both legs during a single session evaluation: foot dorsum TcPO2 at 45 degrees using laser-Doppler, ankle-brachial index using Doppler ultrasound (ABI), and pulsatile leg blood flow using magnetic resonance flowmetry; cardiac output was determined using transthoracic bioimpedance. The diabetic and nondiabetic groups were determined to have nonsignificant differences (mean +/- SEM, DM vs NODM) with respect to age (63.3 +/- 1.1 vs 60.1 +/- 1.5 years), cardiac output (5.5 +/- 0.2 vs 5.5 +/- 0.2 l/min), leg blood flow (1.6 +/- 0.05 vs 1.7 +/- 0.06 ml/min/100 cc) and ABI. Although macrocirculatory values were equivalent, microvascular function indicators were significantly reduced in the diabetic group: TcPO2 (51.9 +/- 1.4 vs 62.9 +/- 1.3 mmHg); MVR 76.7 +/- 1.5 vs 84.9 +/- 0.9%) and were correlated only in diabetics (r2 = 0.48, P < 0.001). The findings suggest a primary linkage between the diabetic TcPO2 deficit and the microcirculatory submaximal vasodilatory response, with little if any role of macrocirculatory factors.