Methylglyoxal is associated with changes in kidney function among individuals with screen-detected Type 2 diabetes mellitus.

AIMS: The glycolysis-derived metabolite methylglyoxal has been linked to clinical microvascular complications, including diabetic nephropathy. We aimed to further investigate the hypothesis that methylglyoxal is involved in decline in renal function by assessing the associations between measures of renal function during a 6-year follow-up in 1481 people with screen-detected Type 2 diabetes, as part of the Danish arm of the ADDITION-Europe trial (ADDITION-DK). METHODS: Biobank serum samples collected at ADDITION-DK baseline (2001-2006) and follow-up (2009-2010) were used in the current analysis of methylglyoxal. We assessed cross-sectional baseline and longitudinal associations between methylglyoxal and urinary albumin-to-creatinine ratio (ACR) or estimated GFR (eGFR), and between methylglyoxal and categories of albuminuria or reduced eGFR. RESULTS: Baseline methylglyoxal was positively associated with ACR at baseline (12% higher ACR per doubling in methylglyoxal levels), and change in methylglyoxal during 6 years of follow-up was inversely associated with change in eGFR (-1.6 ml/min/1.73 m2 per doubling in methylglyoxal change), in models adjusted for age, sex, HbA1c , systolic blood pressure, anti-hypertensive treatment, LDL-cholesterol, lipid-lowering treatment, C-reactive protein and smoking. CONCLUSIONS: In a population of people with screen-detected Type 2 diabetes, we observed associations between methylglyoxal and markers of renal function: 6-year change in methylglyoxal was inversely associated with 6-year change in eGFR. Also, methylglyoxal at baseline was positively associated with ACR at baseline. Our study lends further support to a role for methylglyoxal in the pathogenesis of diabetic nephropathy.

The role of serum methylglyoxal on diabetic peripheral and cardiovascular autonomic neuropathy: the ADDITION Denmark study.

AIMS: Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are common diabetic complications and independent predictors of cardiovascular disease. The glucose metabolite methylglyoxal has been suggested to play a causal role in the pathogeneses of diabetic peripheral neuropathy and possibly diabetic cardiovascular autonomic neuropathy. The aim of this study was to investigate the cross-sectional association between serum methylglyoxal and diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the ADDITION-Denmark study with short-term screen-detected Type 2 diabetes (duration ~ 5.8 years). METHODS: The patients were well controlled with regard to HbA(1c), lipids and blood pressure. Cardiovascular autonomic neuropathy was assessed by measures of resting heart rate variability and cardiovascular autonomic reflex tests. Diabetic peripheral neuropathy was assessed by vibration detection threshold (n = 319), 10 g monofilament (n = 543) and the Michigan Neuropathy Screening Instrument questionnaire (n = 966). Painful diabetic neuropathy was assessed using the Brief Pain Inventory short form (n = 882). RESULTS: No associations between methylglyoxal and cardiovascular autonomic reflex tests or any measures of diabetic peripheral neuropathy or painful diabetic neuropathy were observed. However, a positive association between methylglyoxal and several heart rate variability indices was observed, although these associations were not statistically significant when corrected for multiple testing. CONCLUSION: Serum methylglyoxal is not associated with cardiovascular autonomic neuropathy, diabetic peripheral neuropathy or painful diabetic neuropathy in this cohort of well-treated patients with short-term diabetes.

The pro-inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is associated with incident type 2 diabetes among overweight but not obese individuals with impaired glucose regulation: effect modification by smoking and body weight status.

AIMS/HYPOTHESIS: Recent evidence links the soluble urokinase plasminogen activator receptor (suPAR), a stable biomarker of systemic immune activation, to several chronic diseases, including type 2 diabetes. suPAR is also associated with adiposity and smoking. We hypothesised that this biomarker would be linked to incident type 2 diabetes in individuals with impaired glucose regulation and that this association would be modified by smoking and body weight status. METHODS: The study included 1,933 participants with impaired glucose regulation, who were drawn from the Danish arm of the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION) and for whom data on suPAR, BMI and smoking were available. Logistic regression analysis was used to estimate the odds for incident type 2 diabetes per twofold increase in suPAR levels. Interactions between both smoking and body weight status and suPAR were tested. RESULTS: During a 3-year follow-up (599 incident diabetes cases), there was a 48% overall increase in the odds of developing type 2 diabetes per twofold increase in suPAR (p = 0.006). This association was modified by body weight status in overweight, but not in obese individuals (OR 2.36, 95% CI 1.48, 3.76 in overweight group), and by smoking status (OR 2.05, 95% CI 1.20, 3.51 in non-smokers). After adjustment for other diabetes risk factors, the association between suPAR and type 2 diabetes was attenuated in the whole sample and among non-smokers, but remained robust among overweight participants. CONCLUSIONS/INTERPRETATION: suPAR may be a good novel biomarker for systemic sub-clinical inflammation and immune activation linked to incident type 2 diabetes risk in overweight individuals and non-smokers. The observed interactions with adiposity and smoking should be investigated further.

Fibrinogen substitution improves whole blood clot firmness after dilution with hydroxyethyl starch in bleeding patients undergoing radical cystectomy: a randomized, placebo-controlled clinical trial.

SUMMARY BACKGROUND: Infusion of artificial colloids such as hydroxyethyl starch (HES) induces coagulopathy to a greater extent than simple dilution. Several studies have suggested that the coagulopathy could be corrected by substitution with a fibrinogen concentrate. OBJECTIVES: The aims of the present prospective, randomized, placebo-controlled trial were to investigate the hemostatic effect of a fibrinogen concentrate after coagulopathy induced by hydroxyethyl starch in patients experiencing sudden excessive bleeding during elective cystectomy. METHODS: Twenty patients were included. Blood loss was substituted 1:1 with HES 130/0.4. At a dilution level of 30%, patients were randomly selected for intra-operative administration of a fibrinogen concentrate or placebo. The primary endpoint was maximum clot firmness (MCF), as assessed by thromboelastometry. Secondary endpoints were blood loss and transfusion requirements, other thromboelastometry parameters, thrombin generation and platelet function. RESULTS: Whole-blood MCF was significantly reduced after 30% dilution in vivo with HES. The placebo resulted in a further decline of the MCF, whereas randomized administration of fibrinogen significantly increased the MCF. Furthermore, only 2 out of 10 patients randomly chosen to receive fibrinogen substitution required postoperative red blood cell transfusions, compared with 8 out of 10 in the placebo group (P = 0.023). Platelet function and thrombin generation were reduced after 30% hemodilution in vivo, and fibrinogen administration caused no significant changes. CONCLUSIONS: During cystectomy, fluid resuscitation with HES 130/0.4 during sudden excessive bleeding induces coagulopathy that shows reduced whole-blood maximum clot firmness. Randomized administration of fibrinogen concentrate significantly improved maximum clot firmness and reduced the requirement for postoperative transfusion.

Comparison of degrees of left ventricular dilation within three hours and up to six days after onset of first acute myocardial infarction.

Following an acute myocardial infarction (AMI) there is immediate deterioration of contractility in the infarcted left ventricular (LV) wall. This can be followed by regional dilation (expansion) as well as global remodeling. We examined 35 consecutive patients--with no history of myocardial ischemia--who were admitted to hospital within 3 hours after initial symptoms and with ST-segment changes on an electrocardiogram consistent with transmural ischemia. Echocardiography was performed at admission, and at 6 hours, 12 hours, 24 hours, 3 days, and 6 days after onset of the AMI. Within 3 hours after onset of symptoms an increase in both end-diastolic volume index (EDVI) and end-systolic volume index (ESVI) was found in both anterior and inferior infarcts when compared with healthy controls (mean +/- SD EDVI: 99 +/- 13 ml/m2 [anterior], 69 +/- 17 ml/m2 [inferior], 51 +/- 15 ml/m2 [controls], p < or = 0.00001; ESVI: 62 +/- 12 ml/m2 [anterior], 38 +/- 11 ml/m2 [inferior], 17 +/- 6 ml/m2 [controls], p < or = 0.00001). At all points in time, volumes were larger in anterior infarcts than in inferior infarcts (p < 0.05). The volumes did not change during the 6 days (p > 0.1). Thus, major LV dilation is present within 3 hours after onset of symptoms of first AMI. The dilation is more pronounced in anterior versus inferior infarcts. From 3 hours until day 6 no further changes in LV volumes occurred.

Effects of inspiratory pressure support on oxygenation and central haemodynamics in the normal heart during the postoperative period.

Ten patients without cardiac disease or pulmonary dysfunction were exposed to an inspiratory pressure of 0, 10 and 20 cmH2O, in random order, via a nasal mask during the first postoperative day after scoliotic surgery. These patients were in the supine position, and a BiPAP respiratory assist device was used. Arterial oxygen saturation increased significantly during the application of 10 and 20 cmH2O, while none of the haemodynamic parameters (cardiac output, central venous pressure, right ventricular ejection fraction, right ventricular end diastolic volume, mean pulmonary artery pressure, pulmonary artery wedge pressure, pulmonary vascular resistance) changed significantly, contrary to the findings during continuous positive airways pressure treatment. In addition, the BiPAP was generally well tolerated by the patients.

"Subdural' pressure measurement during craniotomy. Correlation with tactile estimation of dural tension and brain herniation after opening of dura.

In 30 patients subjected to craniotomy, subdural pressure was measured with a 22G/0.8 mm Venflon cannula connected to a pressure transducer system. The measurements were performed after removal of the bone flap and just before opening of the dura. The subdural pressure was correlated with the tactile estimation of dural tension and the tendency to brain herniation after opening the dura. The results indicate that generally there is a poor agreement between the tactile feeling of dural tension and subdural pressure. Thus, in some patients with a relatively high dural pressure the dural tension was evaluated as relaxed. At subdural pressure below 6 mmHg brain herniation never occurred. On the other hand, at tensions over 7 mmHg some brain herniation occurred in all patients, and at tension over 11 mmHg pronounced brain herniation occurred. The method of subdural pressure used in this study is simple, the duration of the measurement is less than 1 min. It is concluded that measurement of subdural pressure before opening of the dura gives important information.

[Surgical treatment of hydronephrosis. Late results after surgery using the Anderson-Hynes method]. / Kirurgisk behandling af hydronefrose. Senresultatet efter operation ad modum Anderson-Hynes.

Twenty-one patients with hydronephrosis mean age 37 years (11-72) were operated using Anderson-Hynes pyeloplasty, without routine use of a nephrostomy catheter. One patient developed urinary leakage postoperatively, which ceased after insertion of a ureteric catheter. Follow-up assessment was performed after a mean observation time of 85 months (44-142). Clinical examination, laboratory investigations, urography and renography were performed preoperatively and at follow-up. No signs of stones or stenosis in the pelvis were found. The patients operated upon before the age of 30 showed improved postoperative renal function. All patients had symptoms preoperatively, but only one had symptoms postoperatively. It can be concluded that the results of surgical intervention in hydronephrosis are excellent, especially in patients below 30 years.

Long-term follow-up of patients with hydronephrosis treated by Anderson-Hynes pyeloplasty.

A series of 21 patients with hydronephrosis (mean age 37 years) underwent an Anderson-Hynes pyeloplasty; a nephrostomy catheter was not used routinely. One patient developed urinary leakage post-operatively but this ceased following insertion of a ureteric catheter. Assessment was carried out after a mean observation time of 85 months. Clinical examination, laboratory investigations, urography and renography were performed pre-operatively and at follow-up. There was no evidence of stones or stenosis in the pelvis. Patients operated upon before the age of 30 years showed improved renal function. All patients had symptoms pre-operatively but only one had symptoms post-operatively. It was concluded that the results of surgical intervention in hydronephrosis are excellent, especially in patients aged less than 30 years.

[Corkscrew esophagus]. / "Proptraekkeresophagus".

"Corkscrew oesophagus" is characterised on the basis of two case reports and attention is drawn to thoracic pain of oesophageal origin. Corkscrew oesophagus is a radiological diagnosis and is characterised by twisted segments in the distal third of the oesophagus. The condition can sometimes be demonstrated endoscopically and it is due to a basic disturbance in the motility of the oesophagus. Painful conditions in the oesophagus are most frequently caused by gastro-oesophageal reflux or disturbances in motility and the latter is frequently complicated by reflux oesophagitis. Pain of oesophageal origin is frequently a diagnosis by exclusion and requires exclusion of ischaemic heart disease. The initial treatment should be directed to the reflux oesophagitis. The diagnosis and information about the origin of the pain and the benign course of the condition will calm the majority of the patients and remove their fear of a possible fatal heart disease.

Does the method of heparinisation influence the biocompatibility of dialysis membranes?

The biocompatibility of cuprophanc haemodialyser membranes was investigated during two haemodialysis sessions in ten stable male chronic haemodialysis patients. In one session heparin was given intravenously, while it was given in the arterial line in the other session, using the same amount of heparin and the same filter. Biocompatibility was determined by measuring platelet and leukocyte counts, plasma beta-thromboglobulin, C3d, elastase, and lactoferrin in the arterial line at 0, 10, and 90 min of dialysis, and in the venous line at 10 and 90 min. Adequate anticoagulation was ensured by determining activated partial thromboplastin time. Platelet counts remained unchanged, whereas leukocyte counts transitorily decreased during dialysis. Plasma beta-thromboglobulin, C3d, elastase, and lactoferrin increased during haemodialysis, but no differences could be found between the two methods of heparinisation. The activation of complement, platelets, and leukocytes seemed to be independent of the mode of heparinisation.

Changing concepts in the management of pathological and impending pathological fractures.

The benefits in the management of pathological fractures by internal fixation are well recognized. However, failures in bone or metal can occur where there is a large amount of bone destruction. Seven of 69 pathological fractures in our series were treated by internal fixation with adjunctive use of methylmethacrylate without failure. This allowed for secure fixation in fractures with large amounts of bone destruction, thus decreasing the patient's pain and allowing earlier mobilization. Neither the effects of radiotherapy on bone involved with neoplasm nor methylmethacrylate are altered when radiotherapy is used after internal fixation and adjunctive use of methylmethacrylate. We believe that an aggressive program of stabilization of these fractures or fixation before actual fracture provides significant patient benefits including reduction of pain, decreased length of hospital stay, reduction of financial expense, and return to as near normal function as possible.