Home-based exercise programmes improve physical fitness of healthy older adults: A PRISMA-compliant systematic review and meta-analysis with relevance for COVID-19.

This systematic review and meta-analysis aimed to examine the effects of home-based exercise programmes on measures of physical-fitness in healthy older adults. Seventeen randomized-controlled trials were included with a total of 1,477 participants. Results indicated small effects of home-based training on muscle strength (between-study standardised-mean-difference [SMD] = 0.30), muscle power (SMD = 0.43), muscular endurance (SMD = 0.28), and balance (SMD = 0.28). We found no statistically significant effects for single-mode strength vs. multimodal training (e.g., combined balance, strength, and flexibility exercises) on measures of muscle strength and balance. Single-mode strength training had moderate effects on muscle strength (SMD = 0.51) and balance (SMD = 0.65) while multimodal training had no statistically significant effects on muscle strength and balance. Irrespective of the training type, >3 weekly sessions produced larger effects on muscle strength (SMD = 0.45) and balance (SMD = 0.37) compared with ≤3 weekly sessions (muscle strength: SMD = 0.28; balance: SMD = 0.24). For session-duration, only ≤30 min per-session produced small effects on muscle strength (SMD = 0.35) and balance (SMD = 0.34). No statistically significant differences were observed between all independently-computed single-training factors. Home-based exercise appears effective to improve components of health- (i.e., muscle strength and muscular endurance) and skill-related (i.e., muscle power, balance) physical-fitness. Therefore, in times of restricted physical activity due to pandemics, home-based exercises constitute an alternative to counteract physical inactivity and preserve/improve the health and fitness of healthy older adults aged 65-to-83 years.

Radiographic diagnosis of proximal caries-influence of experience and gender of the dental staff.

OBJECTIVES: The aim of this study was to examine the influence of experience and gender on the radiographic detection of proximal caries lesions and on therapeutic decisions. MATERIALS AND METHODS: A survey of 220 examiners (students and employees at three universities and dentists in the field) was taken using a standardized written questionnaire concerning radiographic diagnosis and therapy planning. An expert opinion of four dentists was determined as radiographic reference. A mixed effect logistic regression model was used for statistical evaluation and the odds ratio and p values were calculated (α = 0.05). RESULTS: Examiners with experience had an almost four times greater chance of a correct assessment, if proximal caries lesion was present or not, than examiners with low experience (OR 3.7 (95% CI 2.4-5.8)). No gender-specific differences were discovered (OR women vs. men 0.9 (95% CI 0.6-1.4)). There was a relationship between the severity of the burnout effect on the x-ray and false positive caries diagnosis. Overall, 43% of respondents would plan invasive treatment in the enamel on a patient at low risk of caries and 78% on a high-risk patient. The results showed that the more experienced practitioners would be more likely to postpone restorative therapy on proximal caries until the lesion reached a later stage. CONCLUSIONS: The results of this study suggest that examiner's experience influences the radiographic diagnosis of proximal lesions. No gender-specific differences could be found. CLINICAL RELEVANCE: Examiner's professional experience is an important factor when radiography is included for detection and treatment planning of proximal lesions.

Shot Noise of 1,4-Benzenedithiol Single-Molecule Junctions.

We report measurements of the shot noise on single-molecule Au-1,4-benzenedithiol-Au junctions, fabricated with the mechanically controllable break junction (MCBJ) technique at 4.2 K in a wide range of conductance values from 10(-2) to 0.24 conductance quanta. We introduce a simple measurement scheme using a current amplifier and a spectrum analyzer and that does not imply special requirements regarding the electrical leads. The experimental findings provide evidence that the current is carried by a single conduction channel throughout the whole conductance range. This observation suggests that the number of channels is limited by the Au-thiol bonds and that contributions due to direct tunneling from the Au to the π-system of the aromatic ring are negligible also for high conductance. The results are supported by quantum transport calculations using density functional theory.

Aleglitazar, a dual peroxisome proliferator-activated receptor-α/γ agonist, improves insulin sensitivity, glucose control and lipid levels in people with type 2 diabetes: findings from a randomized, double-blind trial.

The present single-centre, randomized, double-blind, placebo-controlled phase II study investigated the effect of the balanced dual peroxisome proliferator-activated receptor-α/γ agonist aleglitazar on whole-body and liver insulin sensitivity, ß-cell function and other components of cardiometabolic syndrome after 16 weeks of treatment in patients with type 2 diabetes inadequately controlled with metformin monotherapy who received once-daily 150 µg aleglitazar or matching placebo as add-on therapy to metformin. Baseline and 16-week assessments included a two-step hyperinsulinaemic-euglycaemic clamp, followed by a hyperglycaemic clamp, as well as evaluation of glycated haemoglobin (HbA1c), lipids and safety variables. The primary endpoint was change in whole-body insulin sensitivity (M-value) from baseline compared with placebo, derived from the second clamp step. M-value improved significantly from baseline with aleglitazar (n = 16) compared with placebo (n = 24; p = 0.05 for difference between arms). We found statistically significant treatment differences with aleglitazar versus placebo in fasting hepatic insulin resistance index (p = 0.01), and in total glucose disposal (p = 0.03) at the second insulin infusion step. Aleglitazar treatment resulted in significant improvements in HbA1c and lipids and was well tolerated.

Efficacy, safety and tolerability of aleglitazar in patients with type 2 diabetes: pooled findings from three randomized phase III trials.

AIMS: To evaluate the potential efficacy, safety and tolerability of aleglitazar as monotherapy or add-on therapy to metformin or to a sulphonylurea (either alone or in combination with metformin). METHODS: We conducted a pooled analysis of data from three randomized phase III clinical trials of aleglitazar in patients with type 2 diabetes (n = 591). The three studies focused on: (i) aleglitazar alone; (ii) aleglitazar and metformin; and (iii) aleglitazar and sulphonylurea with or without metformin. Patients were randomized to 26 weeks' treatment with aleglitazar 150 µg/day or placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) concentration from baseline to week 26. Secondary endpoints included changes in lipids, fasting plasma glucose and homeostatic model assessment of insulin resistance (HOMA-IR) at week 26. RESULTS: Reductions in HbA1c concentration from baseline to week 26 were statistically significantly greater with aleglitazar than with placebo. Aleglitazar treatment was associated with more beneficial changes in lipid profiles and HOMA-IR values than was placebo. Aleglitazar was generally well tolerated, with no reports of congestive heart failure. The incidence of peripheral oedema was similar in both groups. Change in body weight was +1.37 kg with aleglitazar and -0.53 kg with placebo. Hypoglycaemia was more frequently reported with aleglitazar (7.8%) than with placebo (1.7%), a result probably driven by the type of background medication. CONCLUSIONS: Development of aleglitazar was halted because of a lack of cardiovascular efficacy and peroxisome proliferator-activated receptor-related side effects in patients with type 2 diabetes post-acute coronary syndrome; however, in the present studies, aleglitazar was well tolerated and effective in improving HbA1c, insulin resistance and lipid variables.

Cardiovascular safety of the glucagon-like peptide-1 receptor agonist taspoglutide in people with type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials.

AIMS: To study the short-term cardiovascular effects of the once-weekly glucagon-like peptide-1 receptor agonist taspoglutide. METHODS: We conducted a meta-analysis of individual-participant data from nine randomized controlled trials in the T-Emerge programme, which assessed the efficacy and safety of taspoglutide in type 2 diabetes. Our primary outcome was a composite of death from cardiovascular disease (CVD) and acute myocardial infarction, stroke and hospitalization for unstable angina. RESULTS: Overall, 7056 individuals were included in the analysis, and there were 67 primary endpoint events during 7478 person-years of follow-up (40 vs 27 events in the intervention vs control groups, respectively). The odds ratio for the composite endpoint among people randomized to taspoglutide was 0.94 (95% confidence interval 0.57-1.56), which was robust across multiple subgroups. Longer-term data were not available as the development of taspoglutide was stopped because of gastrointestinal intolerance and serious hypersensitivity reactions. CONCLUSIONS: The available data suggest that short-term, once-weekly administration of taspoglutide was not associated with an excess risk of CVD, and provide insights relevant to the development of other novel once-weekly incretin mimetics.

The nervous and prenervous roles of serotonin in Echinococcus spp.

Serotonin (5-hydroxytryptamine, 5-HT) is an important neuroactive and morphogenetic molecule in several metazoan phyla, including flatworms. Serotoninergic nervous system studies are incomplete and 5-HT function/s are unknown in Echinococcus spp., the flatworm parasites that cause hydatid disease. In the present work, we searched for genes of the serotoninergic pathway and performed immunocytochemical and functional analyses of 5-HT in Echinococcus spp. Bioinformatic analysis using the recently available Echinococcus multilocularis and Echinococcus granulosus genomes suggests the presence of genes encoding enzymes, receptors and transporters participating in 5-HT synthesis, sensing and transport in these parasites. However, some components of the pathway could not be identified, suggesting loss or divergence of parasite homologous genes. The serotoninergic neuroanatomy study performed by confocal scanning laser microscopy on different E. granulosus stages showed an increasing level of complexity when the protoscolex develops towards the adult stage and a progressive diminution when the parasite develops towards the metacestode stage. The role of 5-HT as a neurotransmitter in E. granulosus was evaluated by determining the effect of this substance on protoscolex motility. The addition of 5-HT to protoscoleces induced a significant increase in motility for short time periods. Preincubation with 100 µM citalopram, a known 5-HT transporter inhibitor, abolished the 5-HT-induced increase in motility, indicating that the effect could be mediated by a 5-HT transporter. Incubation of protoscoleces with 5-HT for time periods of several days induced a progressive differentiation towards the metacestode stage. The results indicate that 5-HT could have nervous and prenervous roles during Echinococcus spp. development. Taking into account the important roles of 5-HT in parasite biology and the divergence of 5-HT pathway genes with respect to human counterparts, the serotoninergic system could be considered as an amenable drug target against hydatid disease.

Resistance to powdery mildew in Spanish barley landraces is controlled by different sets of quantitative trait loci.

Twenty-two landrace-derived inbred lines from the Spanish Barley Core Collection (SBCC) were found to display high levels of resistance to a panel of 27 isolates of the fungus Blumeria graminis that exhibit a wide variety of virulences. Among these lines, SBCC145 showed high overall resistance and a distinctive spectrum of resistance compared with the other lines. Against this background, the main goal of the present work was to investigate the genetic basis underlying such resistance using a doubled haploid population derived from a cross between SBCC145 and the elite spring cultivar Beatrix. The population was genotyped with the 1,536-SNP Illumina GoldenGate Oligonucleotide Pool Assay (Barley OPA-1 or BOPA1 for short), whereas phenotypic analysis was performed using two B. graminis isolates. A major quantitative trait locus (QTL) for resistance to both isolates was identified on the long arm of chromosome 6H (6HL) and accounted for ca. 60% of the phenotypic variance. Depending on the B. graminis isolate tested, three other minor QTLs were detected on chromosomes 2H and 7H, which explained less than 5% of the phenotypic variation each. In all cases, the alleles for resistance derived from the Spanish parent SBCC145. The position, the magnitude of the effect observed and the proportion of phenotypic variation accounted for by the QTL on 6HL suggest this is a newly identified locus for broad-based resistance to powdery mildew.

Pioglitazone has anti-inflammatory effects in patients with Type 2 diabetes.

BACKGROUND: Type 2 diabetes is characterized by increased acute phase serum proteins. They are also risk factors for cardiovascular disease. We wanted to study how improvement of glycemic control with pioglitazone or glibenclamide affects their serum concentrations. MATERIALS AND METHODS: A total of 59 patients with Type 2 diabetes (age 57.3+/-1.2 yr, glycosylated hemoglobin (HbA1c) 8.3+/-0.7%, body mass index (BMI) 31.4+/-0.8 kg/m2) participated in the study. They were previously treated either with diet alone or in combination with one oral antihyperglycemic medicine. After a 1-week lead-in period on diet only, the patients were randomized to pioglitazone or glibenclamide. Blood samples for alpha-1-acid glycoprotein (A1GP), Creactive protein (CR P) and serum amyloid A (SAA) were taken before the treatments and during the therapy after 20 and 52 weeks. RESULTS: Baseline A1GP correlated with CR P (r=0.70, p<0.001) and fasting glucose (r=0.32, p<0.02). Baseline CR P correlated with HbA1c (r=0.26, p<0.05) and insulin (r=0.37, p<0.01). The anti-hyperglycemic effect was comparable with HbA1c levels decreasing both in the pioglitazone (from 8.18+/-0.09% to 7.63+/-0.17%, p<0.01) and glibenclamide (from 8.35+/-0.12% to 7.77+/-0.16%, p<0.01) groups. Pioglitazone treatment was associated with a reduction in A1GP at 20 weeks (p<0.001) and at 52 weeks (p<0.05) as compared to baseline. The significance remained also after comparison to glibenclamide therapy (p<0.001 and p<0.05, 20 and 52 weeks respectively). CR P was also more reduced in the pioglitazone group at 20 weeks of treatment (p<0.05). CONCLUSIONS: Inflammatory factors and markers of hyperglycemia are associated in patients with Type 2 diabetes. Pioglitazone treatment results in reduced A1GP concentration suggesting an anti-inflammatory effect.

Isolated oculomotor nerve palsy as the presenting clinical manifestation of a meningeal carcinomatosis: a case report.

We present a previously unreported case of isolated oculomotor nerve palsy as the inaugural clinical sign of meningeal carcinomatosis (MC). Gadolinium-enhanced magnetic resonance images (MRI) were unremarkable. Cerebrospinal fluid (CSF) analysis showed malignant cells consistent with a pulmonary adenocarcinoma; the chest CT revealed a small pulmonary mass in the upper right lobe. This case highlights the importance of considering MC in all patients who develop sudden oculomotor palsy; lumbar punctures should always be performed on patients with normal MRI when other possible causes of oculomotor palsy have been ruled out.

Synthesis and preclinical evaluation of the choline transport tracer deshydroxy-[18F]fluorocholine ([18F]dOC).

11C-labeled choline ([11C]CHO) and 18F-fluorinated choline analogues have been demonstrated to be valuable tracers for in vivo imaging of neoplasms by means of positron emission tomography (PET). The objective of the present study was to evaluate whether deshydroxy-[18F]fluorocholine, ([18F]dOC), a non-metabolizable [18F]fluorinated choline analogue, can serve as a surrogate for cholines that are able to be phosphorylated and thus allow PET-imaging solely by addressing the choline transport system. The specificity of uptake of [18F]dOC was compared with that of [11C]choline ([11C]CHO) in cultured rat pancreatic carcinoma and PC-3 human prostate cancer cells in vitro. In addition, biodistribution of [18F]dOC and [11C]CHO was compared in AR42J- and PC-3 tumor bearing mice. The in vitro studies revealed that membrane transport of both compounds can be inhibited in a concentration dependent manner by similar concentrations of cold choline (IC50 [18F]dOC= 11 microM; IC50 [11C]CHO=13 microM. In vitro studies with PC-3 and AR42J cells revealed that the internalized fraction of [18F]dOC after 5 min incubation time is comparable to that of [11C]CHO, whereas the uptake of [11C]CHO was superior after 20 min incubation time. As for [11C]CHO, kidney and liver were also the primary sites of uptake for [18F]dOC in vivo. Biodistribution data after simultaneous injection of both tracers into AR42J tumor bearing mice revealed slightly higher tumor uptake for [18F]dOC at 10 min post-injection, whereas [11C]CHO uptake was higher at later time points. In conclusion, [18F]dOC is taken up into AR42J rat pancreatic carcinoma and PC-3 human prostate cancer cells by a choline specific transport system. Similar transport rates of [18F]dOC and [11C]CHO result in comparable cellular uptake levels at early time points. In contrast to [18F]dOC, which is transported but not intracellularly trapped, the choline kinase substrate [11C]CHO is transported into tumor cells and retained. Thus, the signal obtained by imaging early after injection is mainly reflecting transport, whereas a valid quantification of choline kinase activity needs imaging at later time points. Further studies have to clarify whether quantification of the transport capacity or the choline kinase activity result in a better pathophysiological correlate and thus is the more useful process for tumor characterization.

Sustained effects of pioglitazone vs. glibenclamide on insulin sensitivity, glycaemic control, and lipid profiles in patients with Type 2 diabetes.

AIMS: This study compared the effects of 52 weeks' treatment with pioglitazone, a thiazolidinedione that reduces insulin resistance, and glibenclamide, on insulin sensitivity, glycaemic control, and lipids in patients with Type 2 diabetes. METHODS: Patients with Type 2 diabetes were randomized to receive either pioglitazone (initially 30 mg QD, n = 91) or micronized glibenclamide (initially 1.75 mg QD, n = 109) as monotherapy. Doses were titrated (to 45 mg for pioglitazone and 10.5 mg for glibenclamide) to achieve glycaemic targets during the next 12 weeks: fasting blood glucose of < or = 7 mmol/l and 1-h postprandial blood glucose of < or = 10 mmol/l. Patients were maintained on the titrated dose for 40 weeks. RESULTS: Pioglitazone significantly increased insulin sensitivity compared with glibenclamide, as assessed by homeostasis model assessment (17.0% vs. -13.0%; P < 0.001), quantitative insulin sensitivity check index (0.011 vs. -0.007; P < 0.001) and fasting serum insulin (-1.3 pmol/l vs. 23.8 pmol/l; P = 0.007). The glibenclamide group had significantly lower HbA1c than the pioglitazone group after 12 weeks of therapy (7.8% vs. 8.3%, P = 0.015), but significantly higher HbA1c after 52 weeks of therapy (7.8% vs. 7.2%, P = 0.001). Pioglitazone significantly (vs. glibenclamide) increased mean HDL-C (P < 0.001), decreased mean triglycerides (P = 0.019), and decreased mean atherogenic index of plasma (AIP; P = 0.001) and mean total cholesterol/HDL-C (P = 0.004), without significantly elevating mean total cholesterol or mean LDL-C compared with glibenclamide. CONCLUSIONS These data suggest that the effects of pioglitazone are more sustained than those of glibenclamide for improving insulin sensitivity in patients with Type 2 diabetes, and that 52 weeks' treatment with pioglitazone has favourable effects on glycaemic control and lipoprotein profile.

Humalog Mix25 improves 24-hour plasma glucose profiles compared with the human insulin mixture 30/70 in patients with type 2 diabetes mellitus.

OBJECTIVE: To compare the effects of Humalog Mix25 (Humalog Mix75/25 in the USA) (Mix25) and human insulin 30/70 (30/70) on the 24-hour inpatient plasma glucose (PG) profile in patients with type 2 diabetes mellitus (T2DM). DESIGN: A randomised, open-label, 8-week crossover study. Study insulins were injected twice daily, 5 minutes before breakfast and dinner. SETTING: Four-week outpatient (dose-adjustment) treatment phase, and 3-day inpatient (test) phase. PATIENTS: Twenty-five insulin-treated patients with T2DM (ages 40-66 years), mean (+/- standard error of the mean) (SEM) HbA1c 7.7% +/- 0.23%, and body mass index (BMI) 29.3 +/- 0.83 kg/m2. OUTCOME MEASURES: 24-hour PG profiles, PG excursions after meals, PG area under the curve (AUC), and 30-day hypoglycaemia rate. RESULTS: The 2-hour PG excursions following breakfast (5.5 +/- 0.34 v. 7.2 +/- 0.34 mmol/l, p = 0.002) and dinner (2.4 +/- 0.27 v. 3.4 +/- 0.27 mmol/l, p = 0.018) were smaller with Mix25 than with 30/70. PG AUC between breakfast and lunch was smaller with Mix25 than with 30/70 (77.6 +/- 3.8 v. 89.5 +/- 4.3 mmol/h/ml, p = 0.001). PG AUC between lunch and dinner, dinner and bedtime, and bedtime and breakfast did not differ between treatments. Pre-meal and nocturnal PG were comparable. The postprandial insulin requirement for lunch meals was supplied equally by the two insulin treatments. The thirty-day hypoglycaemia rate was low (Mix25 0.049 +/- 0.018 v. 30/70 0.100 +/- 0.018 episodes/patient/30 days, p = 0.586) for both treatments. CONCLUSION: In patients with T2DM, Mix25 improved the 24-hour PG profile with lower postprandial PG excursions than with human insulin 30/70.

Localisation of genes for resistance against Blumeria graminis f.sp. hordei and Puccinia graminis in a cross between a barley cultivar and a wild barley (Hordeum vulgare ssp. spontaneum) line.

The aims of this investigation have been to map new (quantitative) resistance genes against powdery mildew, caused by Blumeria graminis f.sp. hordei L., and leaf rust, caused by Puccinia hordei L., in a cross between the barley ( Hordeum vulgare ssp. vulgare) cultivar "Vada" and the wild barley ( Hordeum vulgare ssp. spontaneum) line "1B-87" originating from Israel. The population consisted of 121 recombinant inbred lines. Resistance against leaf rust and powdery mildew was tested on detached leaves. The leaf rust isolate "I-80" and the powdery mildew isolate "Va-4", respectively, were used for the infection in this experiment. Moreover, powdery mildew disease severity was observed in the field at two different epidemic stages. In addition to other DNA markers, the map included 13 RGA (resistance gene analog) loci. The structure of the data demanded a non-parametric QTL-analysis. For each of the four observations, two QTLs with very high significance were localised. QTLs for resistance against powdery mildew were detected on chromosome 1H, 2H, 3H, 4H and 7H. QTLs for resistance against leaf rust were localised on 2H and 6H. Only one QTL was common for two of the powdery mildew related traits. Three of the seven QTLs were localised at the positions of the RGA-loci. Three of the five powdery mildew related QTLs are sharing their chromosomal position with known qualitative resistance genes. All detected QTLs behaved additively. Possible sources of the distorted segregation observed, the differences between the results for the different powdery mildew related traits and the relation between qualitative and quantitative resistance are discussed.

PET imaging of somatostatin receptors: design, synthesis and preclinical evaluation of a novel 18F-labelled, carbohydrated analogue of octreotide.

Because of the excellent nuclear properties of fluorine-18 and the growing interest in somatostatin receptor (sst) scintigraphy with PET, a novel carbohydrated (18)F-labelled sst ligand was developed and preclinically evaluated. Synthesis of N(alpha)-(1-deoxy- D-fructosyl)- N(epsilon)-(2-[(18)F]fluoropropionyl)-Lys(0)-Tyr(3)-octreotate ([(18)F]FP-Gluc-TOCA) was completed in approximately 3 h (20%-30% yield). [(19)F]FP-Gluc-TOCA showed no affinity to hsst1 and hsst3, moderate affinity to hsst4 (IC(50): 437+/-84 n M) and hsst5 (IC(50): 123+/-8.8 n M) and very high affinity to hsst2 (IC(50): 2.8+/-0.4 n M). As a result of carbohydration, lipophilicity of [(18)F]FP-Gluc-TOCA was found to be low (lg P(OW)=-1.70+/-0.02). In mice, the tracer was rapidly cleared via renal excretion (kidneys: 8.69%+/-1.09%ID/g) and showed low uptake in liver (0.72%+/-0.14%ID/g) and intestine (1.88%+/-0.52%ID/g) and high tumour uptake (13.54%+/-1.47%ID/g) (all data at 1 h p.i.). Tumour to non-tumour ratios at 60 min p.i. reached 25, 19, 7, 1.6 and 56 for blood, liver, intestine, kidney and muscle, respectively. A similar biodistribution pattern was observed in pancreatic tumour-bearing rats. Tumour uptake in rats was reduced to 36% and 18% of control (30 and 60 min) by co-injection of 500 microg Tyr(3)-octreotide, demonstrating sst-specific uptake. In a first [(18)F]FP-Gluc-TOCA-PET study of a patient with a metastatic carcinoid in the liver the tracer showed superior pharmacokinetics, e.g. rapid urinary excretion and low uptake in liver, kidney and spleen. Multiple liver lesions (SUVs ranging from 21.4 to 38.0) and previously unknown focal uptake in the abdomen (SUV 10.0) were clearly visible. This is the first report on PET imaging using an (18)F-labelled sst binding peptide; it indicates that [(18)F]FP-Gluc-TOCA offers excellent imaging characteristics and allows sst imaging with high tumour to non-tumour contrast.

Basal-bolus insulin therapy in Type 1 diabetes: comparative study of pre-meal administration of a fixed mixture of insulin lispro (50%) and neutral protamine lispro (50%) with human soluble insulin.

AIMS: To ascertain whether pre-meal administration of 50% insulin lispro and 50% neutral protamine lispro (NPL), given as a fixed mixture (Humalog Mix50, human soluble (regular) insulin as a basal-bolus regimen in people with Type 1 diabetes. Both regimens included bedtime human isophane (NPH) insulin. METHODS: This was a multinational, multicentre, randomized, open-label, two-period crossover comparison of two insulin treatments for two 12-week periods in 109 patients with Type 1 diabetes. The protocol provided preliminary evaluations of dose requirements and recommendations for insulin dose adjustment when switching regimens on the basis of blood glucose (BG) values. Eight-point BG profiles, frequency of hypoglycaemia, HbA1c, insulin dose, time of injection, and frequency of snacking were assessed during each treatment. RESULTS: Total daily insulin dose was similar for both treatments, but the total pre-meal doses were higher (P < 0.001) and the bedtime dose of isophane was lower (P < 0.001) with Mix50. The pre-meal dose before breakfast and lunch, although statistically different (P = 0.006 and P < 0.001, respectively), was of similar magnitude, but the pre-evening meal dose was higher with Mix50 (P < 0.001). Median (interquartile range) time of insulin injection before meals was: Mix50 4.2 (25th percentile = 1.0; 75th percentile = 6.3) min, human soluble insulin 24.6 (25th percentile = 16.6; 75th percentile = 30.0) min. Pre-meal and bedtime BG concentrations did not differ between treatments. The BG 2 h after the evening meal was lower with Mix50 (8.40 +/- 2.95 mmol/l vs. 9.60 +/- 3.47 mmol/l) (P = 0.049). BG after breakfast and lunch, mean HbA1c, frequency of hypoglycaemia, frequency of snacks, and body weight were not different. CONCLUSION: The use of Mix50 in a basal-bolus regimen achieved similar control of pre-meal BG to human soluble insulin, and overall glycaemic control and hypoglycaemia risk were equivalent. This suggests that Mix50 can provide an adequate supply of insulin to control BG between meals while providing the convenience of injecting immediately before meals.

Effects of a fixed mixture of 25% insulin lispro and 75% NPL on plasma glucose during and after moderate physical exercise in patients with type 2 diabetes.

OBJECTIVE: To compare the plasma glucose (PG) response with a fixed mixture of 25% insulin lispro and 75% NPL (Mix25), prior to a meal and 3 h before exercise, to human insulin 30/70 (30/70) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Thirty-seven patients were treated in a randomized, open-label, 8-week, two-period crossover study. Mix25 was injected 5 min before breakfast and dinner throughout the study, as was 30/70 on inpatient test days and on outpatient dose titration days. Following the 4-week outpatient phase, patients were hospitalized, and exercised at a heart rate of 120 beats/min on a cycle ergometer two times for 30 min, separated by 30 min rest, starting 3 h after a 339 kcal breakfast. RESULTS: The 2-h postprandial PG was significantly lower with Mix25 ((mean +/- SEM) 10.5 +/- 0.4 mmol/l vs 11.6 +/- 0.4 mmol/l; p = 0.016). Maximum decrease in PG from onset of exercise to end of exercise was significantly less with Mix25 (-3.6 +/- 0.29 mmol/l vs -4.7 +/- 0.31 mmol/l; p = 0.001). The maximum decrease in PG over 6 h, after exercise onset, was significantly less with Mix25 (-4.3 +/- 0.4 mmol/l vs -5.9 +/- 0.4 mmol/l; p < 0.001). The frequency of hypoglycemia (blood glucose (BG) < 3 mmol/l or symptoms) during the inpatient test was not different between treatments. During the outpatient phase, the frequency of patient-recorded hypoglycemia was significantly lower with Mix25 (0.7 +/- 0.2 episodes/30 d vs 1.2 +/- 0.3 episodes/30 d; p = 0.042). CONCLUSIONS: Mix25 resulted in better postprandial PG control without an increase in exercise-induced hypoglycemia. The smaller decrease in PG during the postprandial phase after exercise may suggest a lower risk of exercise-induced hypoglycemia with Mix25 than with human insulin 30/70, especially for patients in tight glycemic control.

Transplantation of an oversized heart.

In response to the limited number of available donors, the criteria for accepting hearts have been expanded. In a 46-year-old female (160 cm, 56 kg) with a body surface area (BSA) of 1.58 m(2), an orthotopic heart transplantation was performed. She received the heart from a 34-year-old male donor (190 cm, 90 kg, BSA 2.58 m(2)). During transplantation, the obvious difference between the donor's heart and the recipient's pericardium did not cause a technical problem. However, the postoperative course was characterized by severe circulation problems. Due to a hemodynamically significant right heart impression, a consecutive pericardectomy had to be performed. After excision of the left and the right side of the pericardium, the patient returned to a stable condition. The consecutive course was without cardiopulmonary problems and the patient was discharged from the hospital 20 days later. The last twelve-month follow-up showed good cardiac function and excellent physical condition. We conclude that an oversized donor heart can be used for heart transplantation as long as the pericardium is left open and a left and right pericardectomy is performed.

Left ventricular reduction for idiopathic dilated cardiomyopathy as alternative to transplant--truth or dare?

BACKGROUND: Although the concept of reducing wall tension a treatment for advanced heart failure is convincing, clinical data from the Batista operation are conflicting. Despite a number of publications, it is not clear whether left ventricular reduction surgery truly benefits patients with idiopathic, dilated cardiomyopathy (DCM). Surgery may reduce wall tension, but the reason for dilation and contractile dysfunction remains. Thus, the potential benefit of the operation may be overshadowed by the natural course of the underlying disease. CASES: We report a series of five cases where left ventricular reduction was performed and physiological geometry was restored in patients with DCM by a modification of Dor's endoventricular patch plasty. All patients demonstrated an improvement in cardiac function immediately after the operation. This improvement was sustained in one of the patients after 18 months of follow-up. Another patient developed severe heart failure due to therapy-resistant ventricular arrhythmia (Lown IV b), and underwent successful transplantation 4 months after ventricular reduction surgery. Left ventricular dilation reoccurred in two patients 9 and 12 months after reduction surgery, and they were listed for transplant. One patient died after 9 weeks due to sepsis and respiratory dysfunction. CONCLUSIONS: Although the endoventricular patch plasty, as used in this study, is well tolerated by most patients with dilated cardiomyopathy, and results in immediate improvement of contractile function, the long-term benefits of this technique for DCM are uncertain. Thus, the technique is currently not an alternative for heart transplantation. However, the procedure may be an option in patients with contraindications for transplantation.