Non-covalent protein-based adhesives for transparent substrates-bovine serum albumin vs. recombinant spider silk.

Protein-based adhesives could have several advantages over petroleum-derived alternatives, including substantially lower toxicity, smaller environmental footprint, and renewable sourcing. Here, we report that non-covalently crosslinked bovine serum albumin and recombinant spider silk proteins have high adhesive strength on glass (8.53 and 6.28 MPa, respectively) and other transparent substrates. Moreover, the adhesives have high visible transparency and showed no apparent degradation over a period of several months. The mechanism of adhesion was investigated and primarily attributed to dehydration-induced reorganization of protein secondary structure, resulting in the supramolecular association of ß-sheets into a densely hydrogen-bonded network.

Effect of partitioning the nonfiber carbohydrate fraction and neutral detergent fiber method on digestibility of carbohydrates by dairy cows.

Many nutrition models rely on summative equations to estimate feed and diet energy concentrations. These models partition feed into nutrient fractions and multiply the fractions by their estimated true digestibility, and the digestible mass provided by each fraction is then summed and converted to an energy value. Nonfiber carbohydrate (NFC) is used in many models. Although it behaves as a nutritionally uniform fraction, it is a heterogeneous mixture of components. To reduce the heterogeneity, we partitioned NFC into starch and residual organic matter (ROM), which is calculated as 100 - CP - LCFA - ash - starch - NDF, where crude protein (CP), long-chain fatty acids (LCFA), ash, starch, and neutral detergent fiber (NDF) are a percentage of DM. However, the true digestibility of ROM is unknown, and because NDF is contaminated with both ash and CP, those components are subtracted twice. The effect of ash and CP contamination of NDF on in vivo digestibility of NDF and ROM was evaluated using data from 2 total-collection digestibility experiments using lactating dairy cows. Digestibility of NDF was greater when it was corrected for ash and CP than without correction. Conversely, ROM apparent digestibility decreased when NDF was corrected for contamination. Although correcting for contamination statistically increased NDF digestibility, the effect was small; the average increase was 3.4%. The decrease in ROM digestibility was 7.4%. True digestibility of ROM is needed to incorporate ROM into summative equations. Data from multiple digestibility experiments (38 diets) using dairy cows were collated, and ROM concentrations were regressed on concentration of digestible ROM (ROM was calculated without adjusting for ash and CP contamination). The estimated true digestibility coefficient of ROM was 0.96 (SE = 0.021), and metabolic fecal ROM was 3.43 g/100 g of dry matter intake (SE = 0.30). Using a smaller data set (7 diets), estimated true digestibility of ROM when calculated using NDF corrected for ash and CP contamination was 0.87 (SE = 0.025), and metabolic fecal ROM was 3.76 g/100 g (SE = 0.60). Regardless of NDF method, ROM exhibited nutritional uniformity. The ROM fraction also had lower errors associated with the estimated true digestibility and its metabolic fecal fraction than did NFC. Therefore, ROM may result in more accurate estimates of available energy if integrated into models.

Effect of source of trace minerals in either forage- or by-product-based diets fed to dairy cows: 2. Apparent absorption and retention of minerals.

Eighteen multiparous cows were used in a split-plot replicated Latin square with two 28-d periods to evaluate the effects of source of supplemental Cu, Zn, and Mn (sulfates or hydroxy) on apparent absorption of minerals when fed in either a forage- or by-product-based diet. The by-product diets were formulated to have greater concentrations of NDF and lesser concentrations of starch, and specific ingredients were chosen because they were good sources of soluble fiber and ß-glucans, which bind trace minerals in nonruminants. We hypothesized that hydroxy trace minerals would interact less with digesta and have greater apparent absorption compared with sulfate minerals, and the difference in apparent absorption would be greater for the by-product diet compared with the forage-based diet. During the 56-d experiment, cows remained on the same fiber treatment but source of supplemental trace mineral was different for each 28-d period; thus, all cows were exposed to both mineral treatments. During each period cows were fed no supplemental Cu, Zn, or Mn for 16 d, followed by 12 d of feeding supplemental minerals from either sulfate or hydroxy sources. Supplemental minerals for each of the mineral sources fed provided approximately 10, 35, and 32 mg/kg of supplemental Cu, Zn, and Mn, respectively, for both fiber treatments. Total Cu, Zn, and Mn dietary concentrations, respectively, were approximately 19, 65, and 70 mg/kg for the forage diets and 21, 85, and 79 for the by-product diets. Treatment had no effect on dry matter intake (24.2 kg/d) or milk production (34.9 kg/d). Cows consuming the by-product diets had greater Zn (1,863 vs. 1,453 mg/d) and Mn (1,790 vs. 1,588 mg/d) intake compared with cows fed forage diets, but apparent Zn absorption was similar between treatments. Manganese apparent absorption was greater for the by-product diets compared with the forage diets (16 vs. 11%). A fiber by mineral interaction was observed for Cu apparent absorption, as cows fed hydroxy minerals with forage diets had greater apparent absorption compared with cows fed sulfate minerals; however, the opposite was observed with the by-product diets. Source of supplemental trace minerals and type of fiber in diets affected availability of Cu and Mn and should be considered in ration formulation.

Effect of source of trace minerals in either forage- or by-product-based diets fed to dairy cows: 1. Production and macronutrient digestibility.

Excess rumen-soluble Cu and Zn can alter rumen microbial populations and reduce fiber digestibility. Because of differences in particle size and chemical composition, ruminal and total-tract digestibility of fiber from forage- and by-product-based diets can differ. We hypothesized that, because of differences in mineral solubility, diets with hydroxy rather than sulfate trace minerals would have greater fiber digestibility, but the effect may depend on source of fiber. Eighteen multiparous cows were used in a split-plot replicated Latin square with two 28-d periods to evaluate the effects of Cu, Zn, and Mn source (sulfates or hydroxy; Micronutrients USA LLC, Indianapolis, IN) and neutral detergent fiber (NDF) source (forage diet = 26% NDF vs. by-product = 36%) on total-tract nutrient digestibility. During the entire experiment (56 d) cows remained on the same fiber treatment, but source of supplemental trace mineral was different for each 28-d period so that all cows were exposed to both mineral treatments. During each of the two 28-d periods, cows were fed no supplemental Cu, Zn, or Mn for 16 d followed by 12 d of feeding supplemental Cu, Zn, and Mn from either sulfates or hydroxy sources. Supplemental minerals for each of the mineral sources fed provided approximately 10, 35, and 32 mg/kg of supplemental Cu, Zn, and Mn, respectively, for both fiber treatments. Total dietary concentrations of Cu, Zn, and Mn were approximately 19, 65, and 70 mg/kg for the forage diets and 21, 85, and 79 mg/kg for the by-product diets, respectively. Treatment had no effect on dry matter intake (24.2 kg/d) or milk production (34.9 kg/d). Milk fatty acid profiles were altered by fiber source, mineral source, and their interaction. Cows fed the by-product diets had lower dry matter (65.9 vs. 70.2%), organic matter (67.4 vs. 71.7%), and crude protein digestibility (58.8 vs. 62.1%) but greater starch (97.5 vs. 96.3%) and NDF digestibility (50.5 vs. 44.4%) compared with cows fed the forage treatment. Feeding increased concentrations of by-products decreased total digestible nutrients regardless of mineral source. Feeding hydroxy Cu, Zn, and Mn increased NDF digestibility (48.5 vs. 46.4%) but had no effect on total digestible nutrients.

Short communication: Effects of supplementing diets of Holsteins with copper, zinc, and manganese on blood neutrophil function.

The effects of supplementing diets with sulfate or glycinate Cu, Zn, and Mn on blood neutrophil function were examined in 27 late-lactation Holstein cows having a mean (± standard deviation) days in milk at time of neutrophil assays of 216 ± 31 d. Cows were assigned to 9 blocks of 3 and were grouped by parity, milk production, and days in milk. Cows within each block were randomly assigned to 1 of 3 treatments: (1) control diet devoid of supplemental Cu, Zn, and Mn; (2) diet supplemented with Cu, Zn, and Mn via sulfates; and (3) diet supplemented with Cu, Zn, and Mn via glycinate form. All cows were initially fed a control total mixed ration with basal mineral concentrations of 8 mg/kg of Cu, 35 mg/kg of Zn, and 35 mg/kg of Mn for 30 d. During the treatment period, cows fed diets with mineral supplementation via sulfates or glycinate forms had target total dry matter dietary concentrations of 18 mg/kg of Cu, 60 mg/kg of Zn, and 60 mg/kg of Mn for 30 d. Control cows were fed the control diet devoid of supplemental minerals for an additional 30 d. In vitro neutrophil functions were measured after 30 d on experimental or control diets. Percentage of neutrophils phagocytizing, intracellular kill, and phagocytic index did not differ among treatments. Serum concentrations of Cu, Zn, and Mn were also not affected by dietary treatment after 30 d. Results from this study demonstrated that dietary Cu, Zn, and Mn supplemented either as sulfates or glycinate form for 30 d had no effect on either in vitro blood neutrophil function or serum concentrations of Cu, Zn, and Mn in late-lactation Holstein cows.

Source of supplemental dietary copper, zinc, and manganese affects fecal microbial relative abundance in lactating dairy cows.

Appropriate trace mineral supplementation can improve immune response and hoof health in cattle and at much higher rates of supplementation to swine and poultry can alter microbial colonization of the gut, resulting in improved gut health. Diet can influence fecal microbial excretion in cattle, and the fecal microbiome may serve as a means for assessing gastrointestinal microbial changes. We hypothesized that feeding diets that differed in source of supplemental Cu, Zn, or Mn would alter the relative abundance of fecal microbes in lactating dairy cattle and that organic Zn would have the greatest effect. Twenty-four cows were fed diets devoid of supplemental Cu, Zn, and Mn for a 16-d preliminary phase (basal diet provided 9, 29, and 32 mg/kg of Cu, Zn, and Mn, respectively), and then were randomly assigned to 1 of 3 treatment diets (n = 8 cows/treatment): one group of cows was fed supplemental Cu, Zn, and Mn from sulfate minerals; the second group was fed glycinate minerals; and the third group was fed Cu and Mn sulfate with glycinate Zn. Assayed total dietary concentrations were approximately 21, 73, and 72 mg/kg for Cu, Zn, and Mn, respectively. Milk production (averaged 38.8 kg/d), DMI (averaged 25.8 kg/d), and milk components were not affected by treatment. Fecal DNA was extracted, amplified using a universal primer targeting the V4-V5 hypervariable region of the 16S rRNA gene, and sequenced to compare microbial community composition between treatments. Relative abundances of Treponema species-level operational taxonomic units (OTU) were less for animals fed Cu and Mn sulfate with glycinate Zn compared with sulfates alone, but were similar to animals fed glycinate mineral sources. Relative abundances for exclusive glycinate mineral and sulfate mineral treatments were similar. Treponema OTU and cultured representatives are often associated with bovine digital dermatitis. These data may provide an additional link between organic Zn supplementation and improved hoof health. To our knowledge this is the first report of a dietary treatment decreasing the relative abundance of Treponema OTU in cattle feces; however, the potential benefits of this response on overall animal health and the mechanism for the observed responses are unknown and warrant further investigation.

Refractory status epilepticus.

Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED), i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs) and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits.

Vertical bone volume in the paramedian palate of adolescents: a computed tomography study.

INTRODUCTION: The paramedian palate (PP) has been used as a host site for orthodontic implant anchorage. Available bone and interference of adjacent tooth roots must be considered in identifying the most appropriate locations for implantations in the PP. METHODS: Cone-beam computed tomography (CBCT) scans (NewTom QR-DVT 9000; QR s.r.l., Verona, Italy) were acquired in 183 orthodontic patients (ages, 10-19 years). Views of the PP region were reconstructed at increments posterior from the incisive foramen, and measurements of bone height were made in each reconstruction laterally from the midline to describe the PP. RESULTS: At 4 mm posterior to the incisive foramen and 3 mm lateral to the midline, 93% of the male and 91% of the female subjects met the criterion for implantation. At 8 mm posterior to the incisive foramen and 3 mm lateral to the midline, 86% of the male and 58% of the female subjects met the criterion for implantation. CONCLUSIONS: The PP contains several valid implant host sites in adolescent patients. At 4 mm distal and 3 mm lateral to the incisive foreman, 93.2% of the boys and 91.9% of the girls had sufficient vertical bone depth to host a 3-mm implant with little practical tooth interference. CBCT allows accurate assessment of the entire volume of a proposed implant site.

Predictive factors of vertical bone depth in the paramedian palate of adolescents.

OBJECTIVE: To determine whether a relationship exists between the vertical bone depth in the paramedian palate (PP) of growing patients and age, gender, and palatal morphology. Clinically detectable traits may decrease the need for further imaging prior to implant placement for orthodontic anchorage. MATERIALS AND METHODS: Cone beam computed tomagraphic scans (Newtom-9000, Verona, Italy) were acquired in 183 orthodontic patients (10-19 years old). Vertical bone depth was measured at nine unilateral locations in the PP of each subject. Measurements were analyzed with univariate and multivariate statistical tests. RESULTS: Significant variability in the bone thickness was found among locations and among subjects. Male subjects had significantly greater mean bone thickness in six of the nine locations measured, showing a mean of 1.22 mm more vertical bone than females showed at these locations. Age and palatal measurements did not demonstrate a clinically useful relationship with bone depth. CONCLUSIONS: Age and palatal morphology are not valid predictors of bone height in the PP. Because of the large variability of bone thickness in this region, computed tomographic imaging remains valuable prior to paramedian implant placement in growing individuals. The paramedian palate presents a promising region for palatal implant placements when the midpalatal suture is to be avoided.

Potential influence of timing of low-density lipoprotein cholesterol evaluation in patients with acute coronary syndrome.

OBJECTIVE: To determine the significance of timing of low-density lipoprotein (LDL) cholesterol evaluation in patients with chest pain as it relates to subsequent National Cholesterol Education Program (NCEP) treatment decisions. DESIGN: Prospective, observational study. SETTING: A university-affiliated tertiary care hospital. PATIENTS: Sixty-two patients with coronary heart disease who were not receiving lipid-lowering therapy and whose LDL levels were obtained 25-48 hours after onset of chest pain. INTERVENTION: We evaluated laboratory test results of patients with chest pain admitted to the cardiac care unit to determine risk to patients when LDL levels obtained inappropriately are used to make decisions regarding antihyperlipidemic therapy. MEASUREMENTS AND MAIN RESULTS: Inpatient and outpatient LDL levels were compared, and changes in NCEP treatment decisions analyzed. Differences between inpatient and outpatient LDL levels were significant (p<0.05), which frequently resulted in changes in therapy using the NCEP guidelines. The LDL levels of most inpatients were consistent with NCEP goals for patients with coronary heart disease, whereas the outpatient levels showed a need for drug therapy. CONCLUSION: Lipid values obtained 25-48 hours after hospital admission in patients with acute coronary syndromes do not represent baseline values and may significantly alter the treatment approach; thus, they should not be used to direct drug therapy.

Thoracic aortic dissection in a patient with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease is one of the most common hereditary diseases, and frequently has well defined extrarenal manifestations. Very few cases of aortic aneurysms associated with this disorder are described in literature. We report a 42-year-old male with autosomal dominant polycystic kidney disease presenting with dissecting aneurysm of the thoracic aorta.

The use and abuse of the Periotest for 2-piece implant/abutment systems.

While the Periotest continues to be used in assessing the integrity of implants, there are numerous reports of its inconsistencies. To understand more precisely what the Periotest is actually measuring, a mathematical model was developed that illustrates the effect that various geometric and clinical parameters have on the Periotest value (PTV). In addition, the model was validated with an in vitro experiment. Results of the mathematical model are shown to correlate with those obtained from the experimental test The PTV is very sensitive to the position at which the Periotest impacts the abutment and to angulation of the handpiece. It was shown that a change in position of 1 mm in striking height can produce a difference in PTV of between 1 and 2. Since the angulation of the handpiece can produce a difference in striking position of 2 mm, it must be controlled as well. The model also showed that the Periotest can detect changes in bone height of 0.5 mm.

Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension.

BACKGROUND: Recent hypertension trials have demonstrated the importance of achieving goal blood pressures to reduce the risk of target organ damage. In patients with moderate to severe hypertension, the use of high-dose monotherapy and/or combinations of drugs are necessary to achieve these goals. Fixed-dose combination products may be useful in these patients by reducing the number of daily doses required to control blood pressure. OBJECTIVE: The objective of the present study was to evaluate the efficacy and safety of a therapeutic interchange between high-dose calcium channel blocker therapy and a fixed-dose combination of amlodipine/ benazepril (Lotrel; Novartis Pharmaceuticals, USA) in patients with moderate to severe hypertension. METHODS: A total of 75 patients were switched from amlodipine (n = 25), felodipine (n = 25), and nifedipine-GITS (n = 25) to amlodipine/benazepril. Twenty-eight of the 75 patients (37%) were taking either a beta-blocker or a diuretic in addition to the high-dose calcium channel blocker prior to the switch. Blood pressure control, side effects and the cost of the therapeutic interchange were evaluated in the year following the therapeutic interchange. RESULTS: Sixty-six of the 75 (88%) patients were successfully switched with maintenance of blood pressure control and without the development of new dose-limiting side effects. Reasons for treatment failure after the therapeutic interchange included loss of blood pressure control in five patients and the development of new dose-limiting side effects in four patients. These side effects included cough in three patients and rash in one patient. After accounting for differences in drug acquisition cost and costs related to the switch (clinic and emergency room and laboratory tests), a cost savings of $16030 for all 75 patients was realised in the first year. The per patient-per year cost savings was $214. CONCLUSIONS: Our data indicate that a therapeutic interchange from selected high-dose calcium channel blockers to a fixed-dose combination of amlodipine/ benazepril can be successfully accomplished in the majority of patients.

Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial.

CONTEXT: Incidence of end-stage renal disease due to hypertension has increased in recent decades, but the optimal strategy for treatment of hypertension to prevent renal failure is unknown, especially among African Americans. OBJECTIVE: To compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine), and a beta-blocker (metoprolol) on hypertensive renal disease progression. DESIGN, SETTING, AND PARTICIPANTS: Interim analysis of a randomized, double-blind, 3 x 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease (glomerular filtration rate [GFR] of 20-65 mL/min per 1.73 m(2)) enrolled between February 1995 and September 1998. This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000. INTERVENTIONS: Participants were randomly assigned to receive amlodipine, 5 to 10 mg/d (n = 217), ramipril, 2.5 to 10 mg/d (n = 436), or metoprolol, 50 to 200 mg/d (n = 441), with other agents added to achieve 1 of 2 blood pressure goals. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of change in GFR; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50% or 25 mL/min per 1.73 m(2), end-stage renal disease, or death. RESULTS: Among participants with a urinary protein to creatinine ratio of >0.22 (corresponding approximately to proteinuria of more than 300 mg/d), the ramipril group had a 36% (2.02 [SE, 0.74] mL/min per 1.73 m(2)/y) slower mean decline in GFR over 3 years (P =.006) and a 48% reduced risk of the clinical end points vs the amlodipine group (95% confidence interval [CI], 20%-66%). In the entire cohort, there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups (P =.38). However, compared with the amlodipine group, after adjustment for baseline covariates the ramipril group had a 38% reduced risk of clinical end points (95% CI, 13%-56%), a 36% slower mean decline in GFR after 3 months (P =.002), and less proteinuria (P<.001). CONCLUSION: Ramipril, compared with amlodipine, retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria.

Amlodipine/benazepril: fixed dose combination therapy for hypertension.

Myocardial infarction, stroke, heart failure and end-stage renal disease have all been linked to inadequate control of blood pressure. Despite overwhelming evidence that uncontrolled hypertension is responsible for a sizeable number of adverse health-related outcomes, control of the disease remains considerably suboptimal. Available data demonstrate that in order to achieve adequate blood pressure control, a large number of patients require therapy with more than one medication. Fixed dose combination antihypertensive therapy has many advantages over other treatment options. Positive effects on blood pressure control, rates of adherence, adverse effects and cost have been identified. Amlodipine/benazepril (Lotrel), Novartis) is a fixed dose combination product indicated for the treatment of hypertension. Although not currently recommended as first-line therapy, studies confirm that this combination of a long-acting calcium antagonist and an angiotensin-converting enzyme (ACE) inhibitor possesses substantial blood pressure lowering capabilities. Whereas adverse events tend to become more frequent with increasing doses of antihypertensive monotherapy, the rate of adverse events attributed to amlodipine/benazepril in clinical trials often correlates with rates ascribed to placebo. Amlodipine/benazepril is capable of sustaining blood pressure control over a 24 h period and appears to be minimally affected by an occasional dose omission. Unlike the older calcium antagonists, amlodipine is unlikely to cause alterations in myocardial contractility. Additionally, the amlodipine/benazepril combination product costs less than the same therapy administered as the individual components. It is, therefore, reasonable to consider therapy with amlodipine/benazepril in appropriate patients after an adequate trial of antihypertensive monotherapy.

A measure of patient empowerment in hospital environments catering for older people.

AIM: The principal aim of this research was to develop a valid and reliable measure of patient empowerment and disempowerment in hospital environments catering for older people. Rationale. It is argued that empowerment is linked to Learned Mastery (Peterson, Maier & Seligman 1993) and increasing patient independence, whilst disempowerment is linked to Learned Helplessness (Seligman 1975) and increasing patient dependence. Consequently, the development of a measure of these concepts would represent a valuable quality assurance tool. METHOD: Measures were developed using the 'act frequency approach' of Buss and Craik (1983) whereby registered nurses (n=38) were asked to nominate empowering and disempowering acts relevant to interactions between staff and older patients. The resulting lists of 98 acts for each disposition were hypothetically judged by older hospitalized people (n=20) as to the extent they would be either 'control giving' (empowering acts) or 'control taking' (disempowering acts) if personally experienced. The twenty highest scoring acts in each category were incorporated into the Patient Empowerment Scale. RESULTS: Using this scale, older hospitalized people (n=102) resident on five different hospital wards were asked to judge how often they had encountered each act over a predetermined period of time. Wards varied in speciality including acute medicine, surgery and elderly care rehabilitation. The ward scoring lowest on the PES (i.e. the least empowering) was the elderly care rehabilitation ward. Moreover, this ward showed an inverse correlation between participant age and exposure to empowering care. Alpha scores ranged from 0.74 to 0.87 for empowerment and 0.65 to 0.87 for disempowerment. CONCLUSION: The PES is offered as a valid and reliable measure of empowerment and disempowerment in hospital settings catering for older people. It enables the identification of environments which place patients at risk of becoming dependent, or alternatively facilitate increasing independence.

Heart rate variability in adolescents and adults with type 1 diabetes.

BACKGROUND: Limited data are available regarding the onset or trajectory of cardiovascular autonomic deterioration in persons with type 1 diabetes. OBJECTIVE: To describe differences in heart rate variability among adolescents with type 1 diabetes, adults with type 1 diabetes who have coexisting renal failure, and adolescent and adult controls. RESEARCH DESIGN AND METHODS: A correlational design was used to compare the status of heart rate variability in adults with type 1 diabetes and renal failure (n = 62); healthy adult controls (n = 67); adolescents with type 1 diabetes (n = 55); and healthy adolescent controls (n = 28). Convenience samples of adult patients with diabetes awaiting kidney or pancreas and kidney transplantation, and adolescents with diabetes were recruited from local university-based clinics. Volunteers served as healthy controls. The short-term R-R variability measures included in this study were changes in heart rate with deep breathing and with the Valsalva maneuver. Twenty-four hour ambulatory heart rate monitoring with power spectral analysis was also obtained to assess longterm R-R variability. RESULTS: Adult patients with type 1 diabetes awaiting transplantation had significantly poorer heart rate variability measures than any of the other three populations studied (p < .0001). Adult control values also were significantly lower than either teenage controls or youths with diabetes (p < .05). Although most long-term R-R variability measures were lower in adolescents with diabetes versus controls, only one measure of parasympathetic modulation (i.e., pNN50) was significantly lower (p = .042). There were significant negative associations between HbA1c and sympathetic modulation (i.e., low hertz) in both the adult group (r= -.406, p = .029) and the adolescent group (r= -.324, p = .025) with diabetes. CONCLUSIONS: Type 1 diabetes is associated with decreased heart rate variability, with the extent of the decrease related to the age of the individual and the severity of the disease.