Peter Jerntorp

Capillary Blood on Filter Paper for Determination of HbA1c by Ion Exchange Chromatography

OBJECTIVE To facilitate HbA1c determination, we evaluated an HbA1c filter paper system enabling capillary blood sampling at home by the patients. RESEARCH DESIGN AND METHODS Capillary blood (two drops) was applied to a filter paper (HbA1c Via Post) and sent to the laboratory where a small disc was punched out on the filter paper. Hemoglobin was eluted from the disc in a buffer containing cysteine to eliminate the interfering glutathione adduct (HbA3) formed during storage. Analysis was performed by ion-exchange chromatography (Mono S, high-performance liquid chromatography), and the eluate was compared with hemolysate of venous blood from 41 patients. The stability of blood impregnated on filter paper was checked at different temperatures over different periods of time. RESULTS There was an excellent agreement (r = 0.99) between HbA1c values from capillary blood on filter paper and HbA1c values from venous blood. HbA1c values were constant when stored on filter paper for 5–7 days at 20–21°C (room temperature) or at 4–6°C (refrigerator) for 10 days as well as at −70°C for several months after blood sampling. A new chromatographic-interfering hemoglobin fraction both from venous and capillary samples was identified as free alpha-chain of hemoglobin. CONCLUSIONS The HbA1c filter paper system enables capillary blood sampling at home, eliminates the need of vein puncture in children and adults, and provides the diabetologist with an HbA1c value when the patient visits the clinic without a need for a previsit phlebotomy.

Increase of Plasma Acetaldehyde: An Objective Indicator of the Chlorpropamide Alcohol Flush

Chlorpropamide alcohol flushing (CPAF) in non-insulin-dependent diabetics (NIDDs) has been reported to be associated with a lower tendency to develop late complications. The flush was thought to be mediated by enkephalins and prostaglandins. Early studies could not correlate CPAF to increased levels of acetaldehyde in blood and the flush was not regarded as an antabuse-like reaction. In this study, the increase of plasma acetaldehyde during the flush in 13 CPAF positive diabetics was significantly (P < 0.005) higher than in 13 CPAF negative diabetics during a CPAF challenge test. The increase of plasma acetaldehyde was reduced to the level of CPAF negative diabetics in three CPAF positive diabetics when they were exposed to alcohol without premedication with chlorpropamide and they did not flush. The normal breakdown of ethanol to acetic acid via acetaldehyde appears to be inhibited by chlorpropamide in the flushers. Acetaldehyde measurement is an objective method to study the chlorpropamide alcohol flush and it appears superior to the measurement of skin temperature.

Clinical utility of serum fructosamine in diabetes mellitus compared with hemoglobin A1c

To evaluate the clinical utility of fructosamine as a mean of monitor glycaemic control, fructosamine and HbA1c were compared in 46 random out-patients visiting a Diabetic Clinic as well as in 25 inpatients admitted to a Diabetes Day Care Unit. In the out-patients, there were a significant correlations between fructosamine and fasting blood glucose (r = 0.75) as well as between fructosamine and HbA1c (r = 0.91). However, when the reference values were considered, interesting differences were found; only 4% of the out-patients showed normal HbA1c values while 39% showed normal fructosamine values. Accordingly, fructosamine and HbA1c evaluate different aspects of glycaemic control. During an admission of 7 days to the Diabetes Day Care Unit no statistical changes in mean blood glucose and fructosamine values occurred. On the other hand, two weeks after discharge from the Unit, not only fructosamine (3.58 +/- 0.16 mmol vs 3.09 +/- 0.08 mmol/l) but also HbA1c (9.52 +/- 0.38% vs 8.33 +/- 0.23%) had improved significantly. Thus HbA1c measures improvements in glycaemic control as early as 3 weeks after changes in treatment. At six weeks after discharge HbA1c (7.63 +/- 0.34%) but not fructosamine (3.02 + 0.14 mmol/l) had improved further. HbA1c is a reliable marker of glycaemic control while the value of fructosamine in clinical practice is unclear.

Pyridoxine reduces cholesterol and low-density lipoprotein and increases antithrombin III activity in 80-year-old men with low plasma pyridoxal 5-phosphate

We have previously observed that pyridoxine treatment reduced plasma total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol concentrations and increased antithrombin III (AT III) activity in atherosclerotic patients with subnormal plasma pyridoxal 5-phosphate (PLP) levels. In order to confirm these results, we selected 17 males with low plasma PLP levels from a group of 122 80-year-old males in whom PLP has been determined. After supplementation with 120 mg of pyridoxine per day for 8 weeks their mean plasma TC and LDL cholesterol concentrations were decreased by 10% (p less than 0.01) and 17% (p less than 0.001), respectively. There was no effect on high-density lipoprotein cholesterol and triglycerides but plasma AT III activity was increased by 6% (p less than 0.05). The mechanism by which pyridoxine acts is unclear but it is hypothesized that pyridoxine-derived PLP may enhance the catabolism of LDL and the activity of AT III by inhibiting their glycosylation.

Precipitating and predisposing factors of acute confusional state among emergency department patients.

The aim of this study was to examine predisposing and precipitating factors of acute confusional state (ACS) retrospectively in medical records of patents examined in an acute medical unit (AMU) who had a preliminary diagnosis of confusion/anxiety. The study comprised all 221 patients who were 65 years old and older among the 18,015 patients examined in the AMU during 1 year who, after a preliminary examination in the AMU, received a diagnosis of confusion/anxiety without any other etiologic diagnosis. Fifty-six cases fulfilled the DSM-III-R criteria for ACS. The control group comprised 165 patients, with anxiety, depression, or psychosis the main finding in 135 cases. Among patients further examined in other departments or for whom consultations were made, the medical records showed that the ACS group had on average 2.6 predisposing factors for ACS, with dementia, cerebrovascular disease, and sensory deficits the most common. Three to six predisposing factors were found among 46% of the ACS patients, compared to 4% of the control group. A precipitating factor of ACS was found in 78% of the ACS cases, and the average number of precipitating factors was 1.6. Dementia (32%), metabolic disturbances (30%), and cardiovascular diseases (16%) were the most frequent precipitating factors among the ACS group. The mortality rates 2 years after examination in the AMU were 32% for the ACS group and 20% for the control group (p <.05). The study suggests that the causes of ACS are often multifactorial and that it is important to seek several precipitating factors when treating this potentially reversible condition.

Aldehyde Dehydrogenase Activity and Large Vessel Disease in Diabetes Mellitus: A Preliminary Study

Type II diabetic subjects, 26 with symptoms and/or signs of large vessel disease (LVD group) and 26 free from clinical vascular disease (FVD group), matched for sex, age, body weight, and duration of diabetes after diagnosis, together with 28 healthy controls participated in a preliminary study on new potential risk factors of large vessel disease. The activity of erythrocyte aldehyde dehydrogenase (ALDH) was significantly higher (P < 0.005) in the LVD than in the FVD group and in the controls, as indicated by a shorter half-life of acetaldehyde in homogenates of erythrocytes and plasma (100 ± 11, 203 ± 28, and 180 ± 21 min, respectively). The results were unaffected by antidiabetes therapy, blood glucose control, alcohol consumption, or by recognized risk factors of angiopathy, such as blood pressure, hyperlipidemia, or smoking. Whether ALDH activity is a primary factor in large vessel disease or is merely a secondary phenomenon is unknown. However, ALDH activity is a critical factor determining chlorpropamide alcohol flush (CPAF), which has been suggested to be an inherited trait in some type II diabetic subjects. In conclusion, high ALDH activity was shown to be associated with an increased risk of large vessel disease in diabetes.

Body composition and dietary habits in 80-year-old smoking men without cardiovascular disease

Eighty-year-old male residents in the community of Malmö were questioned about smoking habits and the occurrence of cardiovascular disease (CVD). Of 1,280 subjects, 122 were selected for further studies and allocated into 4 groups: 1) no CVD, non-smokers; 2) no CVD, smokers; 3) CVD, smokers; and 4) CVD, non-smokers. The smokers had consumed on the average 13 g of tobacco daily for 59 years. Lean body mass (LBM), body fat (BF), % body fat (%BF), and total body water (TBW) were estimated by means of bioelectrical impedance analysis. The mean body weight (BW), LBM, and %BF for all subjects were 74.1 ± 10.2 kg, 58.0 ± 6.8 kg, and 21.3 ± 5.9 kg, respectively.There were no significant differences between all subjects with and without CVD. A lower BW among smokers than in non-smokers was explained by lower BF and %BF in the former. Smokers who had lived predominantly in rural areas had lower BW (6.9 kg) and LBM (5.2 kg) than those from an urban area. A positive correlation was noted between the degree of physical activity and LBM and TBW. Seventeen percent of the smokers exercised regularly. The CVD group had higher plasma cholesterol concentrations than the non-CVD group. Plasma triglycerides showed a positive correlation with BF, %BF and BW, whereas HDL cholesterol was negatively correlated with BF, %BF and BW.It is concluded that smoking is one of several important factors related to body composition, and the penetrance of this factor is still apparent in elderly men. (Aging 3: 269–277, 1991)

A case of dysmyelopoietic syndrome with hypotetraploid karyotype

We present a patient with dysmyelopoietic syndrome and with a complex, hypotetraploid karyotype with numerous structural aberrations.

The chlorpropamide alcohol flush test in diabetes mellitus: Methods for objective evaluation

In order to study the objective value of the chlorpropamide alcohol flush (CPAF) the facial skin temperature and plasma acetaldehyde methods were compared to the visible response (flush/no flush) on standardized CPAF and alcohol challenge tests in 137 type 2 diabetics. Three criteria of CPAF are defined. A visible facial flush was noted in 53% of the diabetics. An increase in facial skin temperature of at least 1.0 degrees C was found in 90% of the subjects with a visible facial flush (flushers), but in only 14% of non-flushers. An increase in plasma acetaldehyde of at least 4 mumol/l was found in 86% of the flushers and in only 15% of non-flushers. Using these criteria to study CPAF all flushers satisfied at least two and 78% fulfilled all three criteria, while no non-flusher fulfilled more than one and 74% satisfied no CPAF criteria. However, with the alcohol test 5% could be identified as alcohol flushers having a falsely positive CPAF-test. In conclusion, it was possible to evaluate the CPAF test objectively with the facial skin temperature and plasma acetaldehyde methods.

Atherosclerosis and acetaldehyde metabolism in blood

Acetaldehyde elimination in blood homogenates and erythrocyte aldehyde dehydrogenase (ALDH) activity were studied in 64 patients operated before the age of 60 years because of symptomatic stenosis of aorta, iliac, or carotid arteries and in 38 healthy controls. The disappearance of acetaldehyde in blood homogenates was biphasic. Patients showed an enhanced elimination of acetaldehyde during the second phase (30-60 min), as compared to controls (T1/2 of acetaldehyde was 103 +/- 47 and 198 +/- 93 min, respectively, P less than 0.001). No correlation was found between ALDH activity and acetaldehyde elimination rate. Acetaldehyde elimination in blood homogenates and [14C]acetaldehyde binding to plasma proteins, hemoglobin, and erythrocyte membranes were studied in 10 patients with atherosclerotic disease and in 12 healthy controls. There was a significant correlation between unstable binding of [14C]acetaldehyde to plasma proteins and the half-life of acetaldehyde in the elimination test (p = 0.74, P less than 0.005). Fractionation of plasma proteins after incubation with [14C]acetaldehyde revealed no difference between patients and controls in the distribution of radioactivity. The binding of [14C]acetaldehyde to hemoglobin or erythrocyte membranes did not differ between patients and controls. These results indicate that patients with angiopathy and an enhanced acetaldehyde elimination in blood have reduced binding of acetaldehyde to plasma proteins. As unstable binding of acetaldehyde to proteins is known to involve free amino groups of amino acid residues, modification of these residues in atherosclerotic disease is conceivable.