Skin microvascular reactivity and subendocardial viability ratio in relation to dyslipidemia and signs of insulin resistance in non-diabetic hypertensive patients.

OBJECTIVE: The aim of this study was to evaluate the influence of dyslipidemia and insulin resistance for the development of microvascular dysfunction in non-diabetic primary hypertension. METHODS: Seventy-one patients with untreated primary hypertension were included. Skin microvascular reactivity was evaluated by laser Doppler fluxmetry with iontophoresis (acetylcholine, ACh and sodium nitroprusside, SNP) and heat-induced hyperemia. Myocardial microvascular function was estimated by the subendocardial viability ratio (SEVR) calculated from pulse wave analysis and applanation tonometry. Triglyceride x glucose (TyG index) and triglyceride/HDL cholesterol ratio were used as measurements of insulin resistance. RESULTS: Skin microvascular dysfunction was associated with low HDL cholesterol, where Ach-mediated peak flux (r = .27, p = .025) and heat-induced peak flux (r = .29, p = .017) related to HDL cholesterol levels. ACh peak flux was inversely related to TG/HDL ratio (r = -.29, p = .016), while responses to local heating and SNP did not. SEVR did not relate to HDL and was unrelated to markers of insulin resistance. These findings were confirmed by multivariable analyses, including potential confounders. CONCLUSIONS: Early microvascular dysfunction can be detected in non-diabetic hypertensive patients and is related to dyslipidemia and to signs of insulin resistance, thus predicting future cardiovascular risk.

Effects of exenatide on microvascular reactivity in patients with type 2 diabetes and coronary artery disease: A randomized controlled study.

OBJECTIVE: We studied the effect of the GLP-1RA exenatide on skin microvascular function in patients with T2DM and CAD. METHODS: Thirty-five patients with T2DM, CAD, and HbA1C 42-86 mmol/mol were randomized to treatment with exenatide or conventional non-GLP-1-based therapy for 12 weeks. Skin microvascular function was examined in the forearm by LDF and iontophoretic application of acetyl choline and SNP, and by PORH at baseline and after 12 weeks. Blood samples for fasting plasma glucose, HbA1C, and lipid profile were collected. RESULTS: At 12 weeks, patients on exenatide showed reductions in HbA1C (from 63.5 ± 13 to 60.7 ± 14 mmol/mol, p = .065), body weight (from 92.6 ± 16 to 89 ± 16 kg, p < .001), and systolic blood pressure (from 141 ± 13 to 134 ± 16 mm Hg, p < .05) as compared to the conventionally treated group. There were no significant changes in skin microvascular function between or within the two groups at follow-up. CONCLUSIONS: Three months' daily treatment with the GLP-1RA exenatide in T2DM patients with CAD showed no significant effects on skin microvascular function or blood glucose control, while this study confirms a reduction in body weight and blood pressure by exenatide, as compared to conventional antidiabetic drug treatment.

Methadone dosing strategies in preterm neonates can be simplified.

AIMS: A dramatic increase in newborn infants with neonatal abstinence syndrome has been observed and these neonates are frequently treated with complex methadone dosing schemes to control their withdrawal symptoms. Despite its abundant use, hardly any data on the pharmacokinetics (PK) of methadone is available in preterm neonates. Therefore we investigated developmental PK of methadone and evaluated current dosing strategies and possible simplification in this vulnerable population. METHODS: A single-centre open-label prospective study was performed to collect PK data after a single oral dose of methadone in preterm neonates. A population PK model was built to characterize developmental PK of (R)- and (S)-methadone. Model-based simulations were performed to identify a simplified dosing strategy to reach and maintain target methadone exposure. RESULTS: A total of 121 methadone concentrations were collected from 31 preterm neonates. A one-compartment model with first order absorption and elimination kinetics best described PK data for (R)- and (S)-methadone. Clearance increases with advancing gestational age and differs between R- and S-enantiomer, being slightly higher for the former (0.244 vs 0.167 L/h). Preterm neonates reached target exposure after 48 hours with currently used dosing schedules. Output from simulations revealed that target exposures can be achieved with a simplified dosing strategy during the first 4 days of treatment. CONCLUSION: Methadone clearance in preterm neonates increases with advancing gestational age and its disposition is influenced by its chirality. Simulations that account for developmental PK changes indicate a shorter methadone dosing strategy can maintain target exposure to control withdrawal symptoms.

The interrelation of endothelial function and microvascular reactivity in different vascular beds, and risk assessment in hypertension: results from the Doxazosin-ramipril study.

There are several non-invasive methods to study endothelial function, but their interrelation and association to cardiovascular risk have not been well evaluated. We studied macrovascular and microvascular endothelial function simultaneously in different vascular beds in relation to cardiovascular mortality risk (Systematic Coronary Risk Evaluation, SCORE) and hypertension induced cardiac organ damage, and their interrelationship. The study investigated 71 hypertensive patients by forearm post-ischemic flow-mediated vasodilation, pulse wave analysis (applanation tonometry) and beta 2-adrenoceptor agonist stimulation for changes in reflection index, skin microvascular reactivity by laser Doppler fluxmetry with iontophoresis and heat-induced hyperaemia, and coronary microvascular function by subendocardial viability ratio (derived from pulse wave analysis). Flow mediated vasodilation related inversely to SCORE (r = 0.34, P = 0.011). Adding microalbuminuria and pulse wave velocity strengthened the associations. Pulse wave reflection changes did not relate to SCORE. Skin microvascular reactivity related inversely to SCORE (peak flux change to sodium nitroprusside r = 0.29, P = 0.033, and to heating r = 0.31, P = 0.018). Subendocardial viability ratio did not relate to SCORE. Endothelial function indices showed no consistent relation to cardiac target organ damage. The agreement between the different methods for evaluating indices of macrovascular and microvascular endothelial function was weak. In conclusion, indices of macrovascular and microvascular endothelial function relate to cardiovascular mortality risk. Their use may improve cardiovascular risk prediction in hypertension. However, methods representing different vascular beds show little interrelationship and are not interchangeable, which may depend on different pathogenetic mechanisms representing different aspects of future cardiovascular risk.Trial registry: NCT02901977.

Kidney function is associated with short-term, mid-term and long-term clinical outcome after coronary angiography and intervention.

BACKGROUND: Patients with kidney dysfunction are at risk of developing ischaemic heart disease. We investigated the association between eGFR and early-, mid- and long-term clinical outcome in patients undergoing coronary angiography and intervention. METHODS: Retrospective study on 4968 patients with complete data on eGFR, 65% male and aged 32-80 years, admitted to Danderyd University Hospital, Stockholm, Sweden for coronary angiography and intervention from 2006 to 2008. Data were censored at 0-30 days, 31-365 days and 366-1825 days of follow-up. RESULTS: Baseline eGFR was strongly associated with all-cause mortality at all three time periods studied with each 10 ml/min per 1.73 m2 increase in eGFR being associated with a ∼30% (p < .001), 25% (p = .002) and 20% (p < .001) decrease in all-cause mortality at 30, 365 and 1825 days respectively. Each 10 ml/min per 1.73 m2 increase in eGFR was associated with a ∼21% (p < .001) decrease in re-hospitalisation for MI at 365 days and a 6% decrease (p = .03) at day 30 for re-vascularisation. CONCLUSIONS: We report a strong association between kidney function and all-cause mortality at both early, mid- and long-term follow-up in patients undergoing coronary angiography and intervention, with eGFR significantly associated with MI-related mortality after one month of follow-up. Kidney function was also shown to be associated with risk for re-vascularisation at one month, indicating mostly procedural-related risk and with new MI at mid-term follow-up. Further research is warranted to explore the mechanisms linking kidney function and cardiovascular disease to improve both the short- and long-term care of these patients.

Association of SP-B gene 9306 A/G polymorphism (rs7316) and risk of RDS.

BACKGROUND: Respiratory distress syndrome (RDS) is a severe pulmonary disease predominantly affects preterm newborns. Polymorphisms of surfactant-protein genes have been mostly evaluated as the candidate contributors in genetics of RDS. However the results are divers in different studies. We aimed at investigating the association of surfactant protein B (SPB) gene 9306 A/G polymorphism (rs7316) with RDS development. METHOD: Three hundred and eighty newborns with gestational age of less than 34 weeks were included in a multicenter case-control study. Respiratory distress (RD) was scored according to Downes' scoring system. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping. RESULT: One hundred and eighty-four neonates showed RDS and 196 did not. Gestational age (GA) was significantly lower in the RDS group compared with the controls. AA genotype and A allele were found more frequently in the RDS group than the controls (96.2% versus 63.8% and 98.1% versus 80.6%, respectively) (p =.0001). CONCLUSIONS: This is the first report of association of SFTPB rs7316 polymorphism with RDS development in Iranian newborns. The current study suggests that GA <28-weeks is the most important factor in predisposition to RDS. Genetic background in terms of SP-B gene might be involved in predisposition to RDS in premature neonates.

Skin microvascular function in patients with type 1 diabetes: An observational study from the onset of diabetes.

BACKGROUND: The development of disturbances in skin microcirculation in type 1 diabetes is not well characterised. We assessed skin microcirculation longitudinally from the onset of diabetes up to 29 years of duration to investigate when such disturbances start. MATERIAL AND METHODS: Seventeen adult patients with type 1 diabetes participated. Skin microvascular function in digit IV of the left hand was investigated by laser Doppler fluxmetry (LDF, arbitrary units [AU]). LDF was carried out at rest and following one-min arterial occlusion. Time to peak LDF (s) and percentage increase of LDF (post-occlusive reactive hyperaemia, PRH%) were determined. Retinopathy was assessed from fundus photographs or ophthalmoscopic recordings. RESULTS: Skin microvascular function remained normal during the first five years. Compared with baseline and a non-diabetic reference group, time to peak LDF was prolonged after 7-9 years of diabetes ( p < 0.01). PRH% was lower than in the reference group after 7-9 years ( p < 0.01), and lower than baseline after 24-29 years of diabetes ( p < 0.05). All but one patient developed retinopathy and the first signs were found after 10 years of diabetes. CONCLUSIONS: Functional disturbances in total skin microcirculation were observed after seven years in patients with type 1 diabetes and preceded diabetic complications such as retinopathy.

Association of SP-C gene codon 186 polymorphism (rs1124) and risk of RDS.

BACKGROUND: Respiratory distress syndrome (RDS) is a severe pulmonary disease that mainly affects preterm neonates. Surfactant-protein genes' polymorphisms have been mostly evaluated as the candidate contributors in genetics of RDS. However, the results are diverse in different populations. We aimed at investigating the association of rs1124 with RDS development. METHOD: Three hundred and thirty five preterm neonates were enrolled in a multicenter case-control study. Respiratory distress (RD) was scored according to Downes' scoring system. Genotyping was performed by PCR-RFLP method. RESULT: One hundred and sixty six neonates showed RDS and 169 did not. Gestational age (GA) was significantly lower in RDS group compared to the controls. In female preterm newborns, AA genotype was found more frequently in RDS group. In RDS group, AA genotype was also associated with milder RD irrespective of gender. In neonates who were born 28-34 weeks, RD appeared to be more severe in the RDS group and males. CONCLUSIONS: This is the first report of association of SFTPC rs1124 polymorphism with RDS development in Iranian newborns. The current study suggests that GA <28-weeks is the most important factor in predisposition to RDS. AA genotype is also, a predisposing factor for the development of RDS in female preterm infants.

The effects of alpha 1-adrenoceptor blockade and angiotensin converting enzyme inhibition on central and brachial blood pressure and vascular reactivity: the doxazosin-ramipril study.

We aimed to study whether inhibition of the renin-angiotensin-aldosterone system has effects on vascular structure and function beyond the effects on blood pressure reduction alone. Patients with mild-to-moderate hypertension (n = 61, age 54 ± 12 years, 34% women) received the angiotensin converting enzyme inhibitor ramipril 10 mg or the alpha 1-adrenoceptor blocker doxazosin 8 mg double-blind for 12 weeks. Aortic blood pressure, pulse wave velocity, and augmentation index were assessed by applanation tonometry. Endothelial function was studied by forearm post-ischemic flow mediated vasodilatation and by pulse wave analysis with beta 2-adrenoceptor agonist stimulation. Skin microvascular reactivity was assessed by laser Doppler fluxmetry and iontophoresis. Treatment with doxazosin or ramipril reduced aortic and brachial blood pressures (all P < 0.001), with greater reductions in aortic than brachial systolic blood pressures (P = 0.021) and aortic/brachial pulse pressure ratio (P = 0.005). Compared to doxazosin, ramipril reduced carotid-femoral and carotid-radial pulse wave velocity (both P < 0.05). Forearm endothelial dependent and independent vasodilatation, assessed by post-ischemic flow mediated vasodilatation and glyceryl trinitrate, and by pulse wave analysis remained unchanged by both doxazosin and ramipril. In addition, skin microvascular endothelial dependent (acetylcholine) and independent vasodilatation (sodium nitroprusside) remained unchanged. In conclusion, ramipril reduced indices of aortic stiffness, suggesting that angiotensin converting enzyme inhibitor therapy may have effects beyond blood pressure reduction. However, treatment did not appear to influence endothelial function. Evidence of endothelial dysfunction and its possible improvement by antihypertensive treatment might require more advanced hypertension.This study is registered at ClinicalTrials.gov (NCT02901977) and at EudraCT (# 2007-000631-25).

The Relationship between Motor Function and Behavioral Function in Infants with Low Birth Weight.

OBJECTIVE: Nowadays, the evaluation of all aspects of infant development is important. However, in practice, some of these assessments, especially those requiring more manipulation on high-risk infants, may impose additional stress on them. Therefore, sometimes it is essential to utilize the results of a developmental assessment for the prediction of some other aspects of development. This study evaluated the relationship between the scores of the behavioral tests and the motor function test. MATERIALS & METHODS: This cross-sectional study and was undertaken in the Neonatal Intensive Care Center and Clinic of Shahid Akbar Abadi Hospital, Tehran, Iran. A group of 50 infants with low birth weights was selected based on the easy non-contingency method and the inclusion criteria, and served as the participants. In order to assess the motor function and the behavioral performance, the motor function test (a test of infant motor performance (TIMP)) and the neonatal behavioral assessment scale (neonatal behavioral assessment scale (NBAS)) were used respectively. TIMP has both stimulation and observation sections. The items include habituation, social interaction, motor system, state organization, state regulation, autonomic system, smile, supplementary items, and the reflex. RESULTS: No significant association was found between the items of the habituation of behavioral testing and the observation of the movement test. There was no statistically significant relationship between the habituation and stimulation sections as well as between the system autonomous of the behavioral test and the observation section of the motor test (P>0.05). The relationship between other variables was statistically significant (P<0.05). CONCLUSION: The scores of some behavioral performance items could be a good predictor of the scores of the motor function items for low birth weight infants in the neonatal period.

Severely impaired microvascular reactivity in diabetic patients with an acute coronary syndrome.

BACKGROUND: Microvascular function is impaired in patients with stable coronary artery disease. The aim was to study microvascular function in patients with diabetes and acute coronary syndrome (ACS). METHODS: Microvascular function was evaluated in 83 patients by laser Doppler fluxmetry (LDF) [PU; perfusion unit, median (interquartile range)] measuring resting LDF and peak LDF following a six min heating of the skin to 44 °C at the foot, respectively. All patients with ACS and without previously known diabetes underwent oral glucose tolerance test. Thirty-nine patients with type 2 diabetes mellitus free from coronary artery disease served as controls. RESULTS: Peak LDF was significantly (P = 0.03) lower in patients with ACS and diabetes (n = 22; 72 (52)) and diabetes without coronary artery disease (n = 39; 69 (51)) as compared to patients with ACS without diabetes (n = 46; 97 (60)), and patients without ACS (n = 15; 140 (121)), respectively. Patients with ACS (n = 68) had significantly (P = 0.04) lower peak LDF (92 (49)) as compared to patients without ACS (n = 15) (140 (121)). CONCLUSION: Microvascular reactivity is severely impaired in patients with diabetes and ACS. Diabetes has a major influence on microvascular function in patients with coronary artery disease.

A Comparison of Early Ibuprofen and Indomethacin Administration to Prevent Intraventricular Hemorrhage Among Preterm Infants.

Intraventricularhemorrhage (IVH) is one of thecommon morbidities among preterm neonates. In thepresentstudy, we set out to evaluate the efficacy of two prophylactic modalities (ibuprofen and indomethacin prophylaxis) for prevention of IVH in our local setting. A prospective study was carried out in Akbar-Abadi Hospital, Tehran-Iran (2013-2014). Ninety-six preterm neonates who cared in closed incubator entered the study. Neonates randomly assigned into 3 groups; control, oral indomethacin (0.2 mg/kg indomethacin daily for 3 days) and oral ibuprofen (10,5,5 mg/kg ibuprofen every 24 hours during 3) administration. For all subjects brain sonography examination was performed in 3rd day, first, 2nd week of life and when infants reached to 36 and 42 weeks of postmenstrual age. The IVH prevalence and the effectiveness of the drugs among groups were statistically assessed. Of all 93 subjects; 14 cases had IVH (15.1%). IVH was significantly more frequent in the controls than in other groups (P=0.049). Prophylactic treatment could significantly decrease the incidence of grade 3 or 4 IVH in experimental groups (P=0.008). There were no significant differences between the three experimental groups with respect to theincidence of GI bleeding, Oliguria, renal dysfunction or NEC (P>0.05). This study demonstrates that low-dose prophylactic indomethacin and ibuprofen are equally associated with a reduction of IVH without any significant side effects like renal dysfunction, GI bleeding or NEC.

The Relationship between Maternal Vitamin D Deficiency and Low Birth Weight Neonates.

OBJECTIVE: Maternal hypovitaminosis D may impair fetal growth and cause adverse pregnancy outcomes including intrauterine growth restriction and neonatal low birth weight. The aim of this study is to evaluate the relationship between maternal vitamin D status and neonate's birth weight. MATERIALS AND METHODS: A cross-sectional, descriptive analytical study was carried out in the nursery ward of 2 hospitals (Tehran-Iran) during one year (January 2011- January 2012). One hundred and two neonates were categorized into two groups, neonates with birth weight< 2500 gr (n=52) and neonates with birth weight>2500 gr (n = 50). Data regarding medical history, physical examination and anthropometric measurements of neonates were noted in a questionnaire. Birth time blood samples of their mothers were analyzed for serum 25-(OH)-vitamin D by ELISA method. Maternal vitamin D status was compared in two groups. RESULTS: Mean maternal vitamin D (vit D) level was 31.46 nmol/L. Forty eight percent of mothers had vitamin D deficiency, 27.5% had vit D insufficiency and 24.5% were normal. Mean maternal vitamin D level of LBW neonates was lower than other group; 25.05 vs. 38.13 (p = 0.001). All mothers of neonates with head circumference ≤ 33 cm also had vitamin D deficiency (p = 0.007). CONCLUSION: Maternal Vitamin D deficiency may increase the risk of low birth weight neonate and modifying maternal nutrition behavior and their vit D level could be beneficial on pregnancy outcome.

Long-term clinical outcome in patients with acute coronary syndrome and dysglycaemia.

BACKGROUND: Diabetes and impaired glucose tolerance (IGT) are major risk factors for atherosclerosis including coronary artery disease (CAD). The present study's aim was to investigate the importance of glucose tolerance for long-term clinical outcome in patients with acute coronary syndrome (ACS). METHODS: A total 1062 consecutive patients, 781 men and 281 women, aged 32-80 years, admitted to the coronary care unit at Danderyd University Hospital, Stockholm, for ACS from 2006 to 2008 were included. At discharge, the patients were categorized according to an oral glucose tolerance test (OGTT) as having normal glucose tolerance (NGT), n = 295 (28%); impaired fasting glucose (IFG) and IGT, n = 299 (28%); diabetes discovered by OGTT, n = 156 (15%); or known diabetes at admission, n = 312 (29%). Mortality and reinfarction rates were studied during a mean follow-up time of 4.0 (±0.8) years. Clinical outcome data were obtained from the Swedish Coronary Angiography and Angioplasty Registry and the Swedish National Registry. RESULTS: There was significantly higher (p < 0.001) mortality within, 30 days, 1 and 3 years in patients with known diabetes as compared to the other groups. During the follow-up, 86 patients (28%) with known diabetes had reinfarction as compared to 36 patients (12%) with NGT and 79 patients (17%) with dysglycaemia (IFG, IGT and diabetes) discovered by OGTT. CONCLUSION: A majority (72% in this study) of patients admitted for ACS have disturbed glucose metabolism, including diabetes, with high prevalence of previously undiagnosed dysglycaemia. Both patients with known diabetes and dysglycaemia discovered by OGTT show a high risk for poor clinical prognosis.

Phenobarbital versus morphine in the management of neonatal abstinence syndrome, a randomized control trial.

BACKGROUNDS: Evaluating the efficacy of the loading and tapering dose of Phenobarbital versus oral Morphine in the management of NAS. METHODS: This randomized, open-label, controlled trial was conducted on 60 neonates born to illicit drugs dependent mothers at Vali-Asr and Akbar-Abadi hospitals, Tehran, Iran, who exhibited NAS requiring medical therapy. The neonates were randomized to receive either: Oral Morphine Sulfate or a loading dose of Phenobarbital followed by a tapering dose. The duration of treatment required for NAS resolution, the total hospital stay and the requirement for additional second line treatment were compared between the treatment groups. RESULTS: The Mean ± Standard Deviation for the duration of treatment required for the resolution of NAS was 8.5 ± 5 days in the Morphine group and 8.5 ± 4 days in the Phenobarbital group (P = 0.9). The duration of total hospital stay was 12.6 ± 5.6 days in the Morphine group and 12.5 ± 5.3 days in the Phenobarbital group (P = 0.7). 3.3 % in the Morphine group versus 6.6 % in the Phenobarbital group required adjunctive treatment (P = 0.5). CONCLUSIONS: There were no significant differences in the duration of treatment, duration of hospital stay, and the requirement for adjunctive treatment, between the neonates with NAS who received Morphine Sulfate and neonates who received a loading and tapering dose of Phenobarbital. TRIAL REGISTRATION: This study is registered at the Iranian Registry of Clinical Trials ( www.irct.ir ) which is a Primary Registry in the WHO Registry Network. (Registration Number = IRCT201406239568N8 ).

The effect of high risk pregnancy on duration of neonatal stay in neonatal intensive care unit.

OBJECTIVE: High risk pregnancies increase the risk of neonatal mortality and morbidity. In order to identify the influence of pregnancy complications on the period of neonatal stay in Neonatal Intensive Care Units (NICUs), an analysis has been carried out in our center. METHODS: In a cross-sectional-descriptive analytical study, the data including NICU length of stay was gathered from 526 medical records of neonates. We also assessed their maternal complications such as premature rapture of membranes (PROM), urinary tract infection (UTI), preeclampsia, oligohydramnios, and twin/triplet pregnancy. Finally we analyzed the relation between variables by SPSS statistics software version 19. The level of significance was considered P<0.05. FINDINGS: 37 of 526 neonatal medical records were excluded. Of the 489 babies hospitalized in NICU for 1 to 54 days; 28.42% born were preterm, 308 with birth weight <2500 gram and 170 with birth weight between 2500 and 4000 gram. There was a significant relation between length of neonatal NICU stay and maternal PROM (P=0.001), preeclampsia (P=0.01), UTI (P=0.02), multiple gestation (P=0.03), and oligohydramnios (P=0.003). We found a positive correlation between numbers of gestation and length of NICU stay (P=0.03). A positive correlation existed between neonatal complication and length of NICU stay (P<0.001). CONCLUSION: By increasing maternal health level and prenatal care services, neonatal outcome can be improved and length of stay in NICUs decreased.

Analgesics and road traffic crashes in senior drivers: an epidemiological review and explorative meta-analysis on opioids.

AIM: To assess the epidemiological evidence associating the use of analgesics with the occurrence of road traffic crashes in senior drivers including a meta-analysis with specific focus on opioids. METHODS: Systematic literature review of articles published between 1991 and 2012 retrieved from major databases using relevant key words. Eligible articles were fully reviewed and the main characteristics and results summarized. The methodological quality was assessed using the Newcastle-Ottawa Scale. Heterogeneity tests and forest and funnel plots were used as part of the meta-analysis on opioids. RESULTS: From the potentially eligible articles, nine were selected (4 case-control, 1 case-crossover, and 4 cohort studies) of which four were of medium and five of high quality; seven investigated opioids and four non-steroidal anti-inflammatory drugs. Crash involvement (n=7) rather than responsibility (n=2) was investigated. Age and sex were the most common covariates adjusted for. Both opioids and non-steroidal anti-inflammatory drugs showed mixed results including differences across estimates between and within studies. A marginal positive effect was observed in the pooled analyses on opioids (n=6, OR 1.20; 95% CI 1.08-1.32). CONCLUSIONS: The evidence is unconvincing in terms of number of studies, control of major confounders, and consistency of the results. The effect seen for opioids can be attributed to the lack of adjustment of key confounders such as concomitant illness or the consumption of alcohol or other psychoactive medications. There is a need for more efficient designs like larger population-based retrospective cohorts and nested case-control or case-crossover studies based on registers of high quality allowing adjustment for these factors and for the selection of unequivocal outcomes (e.g. drivers' responsibility) to produce more persuasive empirical evidence.

Increased Urine IgM and IgG(2) Levels, Indicating Decreased Glomerular Size Selectivity, Are Not Affected by Dalteparin Therapy in Patients with Type 2 Diabetes.

Fifty-four type 2 diabetic patients with neuroischemic foot ulcers were randomised to treatment with 5000 IU of dalteparin, (n = 28), or physiological saline, (n = 26), once daily until ulcer healing or for a maximum of 6 months. Thirty-three patients had normo-, 15 micro-, and 6 macroalbuminuria. The urinary levels of IgM and IgG(2) were elevated in 47 and 50 patients, respectively. Elevated urinary levels of IgM and IgG(2) indicate decreased glomerular size selectivity. Urine IgM levels were associated with IGF-1/IGFBP-1 and IGFBP-1 levels. Dalteparin treatment increased urinary levels of glycosaminoglycans (P < 0.001) and serum IGFBP-1 (P < 0.05) while no significant effects were seen in any of the other studied parameters. In conclusion, dalteparin therapy in patients with type 2 diabetes had no effects on urinary levels of albumin, IgM, or IgG(2) despite significantly increased glycosaminoglycans in urine. Elevated urinary levels of IgM and IgG(2) might be more sensitive markers of renal disease than albuminuria in patients with type 2 diabetes and antihypertensive therapy.

Strict glycaemic control improves skin microcirculation in patients with type 2 diabetes: a report from the Diabetes mellitus And Diastolic Dysfunction (DADD) study.

BACKGROUND: Microcirculatory and endothelial dysfunction are signs of cardiovascular engagement in patients with type 2 diabetes. This study tested whether glucose normalisation may reverse this. METHODS: Thirty-nine T2DM patients (age 61±7 years, 58% females) with signs of mild diastolic dysfunction were randomised to strict glucose control based on insulin (I-group; n=21) or oral agents (O-group; n=18) for four months. Skin microcirculation was studied with laser Doppler fluxmetry and endothelial function with brachial artery flow-mediated dilatation. RESULTS: Glucose control improved (reduction of HbA(1c) I-group = -0.5%; O-group -0.7%; p=0.69). Microcirculation improved in the entire group (n=39) determined by foot laser Doppler fluxmetry (32.2±13.6 vs. 35.3±13.1 perfusion units; p<0.001) and laser Doppler fluxmetry following heating (68.8±34.0 vs. 69.3±25.1 PU; p=0.007). Improvement was more consistent with oral agents than insulin. Endothelial function expressed as flow-mediated dilatation decreased in the I-group (6.0±2.2 to 4.7±3.0%; p=0.037) but remained unchanged in the O-group (4.8±2.3 to 5.0±3.7%; n.s.). CONCLUSIONS: Glycaemic normalisation improved skin microcirculation but not endothelial function in patients with type 2 diabetes with mild cardiovascular engagement.

Comparison of venous and arterial blood sampling for the assessment of platelet aggregation with whole blood impedance aggregometry.

Platelet monitoring is presently under evaluation in the clinic as a tool to improve antiplatelet treatment in patients with coronary artery disease (CAD). Measuring platelet function has, however, many inherent problems. It is important not only to evaluate the method used, but also to evaluate and standardize sampling and sample handling. As platelet monitoring is often performed in connection to coronary angiography and percutaneous coronary interventions, arterial sampling may be more convenient. However, in the outpatient follow-up setting venous sampling is, for obvious reasons, more practical and convenient. In the present study we compared platelet aggregation in blood collected from the arterial sheath to blood collected from the antecubital vein using multiple electrode aggregometry in whole blood in 28 patients with CAD. We found that sampling from artery and vein give similar data and that an identical number of patients with insufficient antiplatelet responses ('low responders' to aspirin and clopidogrel, respectively, according to predefined criteria) were detected with respect to adenosine diphosphate induced and arachidonic-acid induced aggregation. Thus both arterial and venous blood samples can be used in the monitoring of platelet function when multiple electrode aggregometry is applied to detect 'low responders'.