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Biomedical subjects

J O Jeppsson

Publications and source records attributed to J O Jeppsson.

At least 19 recordsLinked to original sources
PubMed1998

[Drunken driver examinations. CD-transferrin is a valuable marker of alcohol consumption].

The article reports findings in a study of 198 subjects attending a psychiatric out-patient clinic, with known or suspected high alcohol consumption during a 12-month period, about half of whom had had their driving licences revoked. The level of carbohydrate-deficient transferrin (CDT) was found to be a valuable marker of alcohol consumption, and a useful adjunct to the measurement of liver enzymes. Both GGT (gamma-glutamyltransferase) and CDT levels were significantly higher in high alcohol consumers than in low consumers. Alcohol the two markers did not differ from each other in statistical significance, CDT was associated with greater sensitivity and specificity; the sensitivity of CDT was 69% for men and 79% for women, as compared with 62% and 40%, respectively, for GGT; the specificity of CDT was 81% for men and 100% for women, as compared with 82% and 72%, respectively, for GGT. Together, GGT and CDT detected 91% of the male and 93% of the female high consumers. Among younger men, CDT values were higher in the subgroup with a history of traffic offences than in the subgroup without such a history, thus suggesting that CDT levels may be increased by heavy weekend beer consumption. A few cases of false-positive CDT results were found to be attributable to genetic anomalies of the transferrin molecule. Cases characterised by disparity between the CDT level and the clinical picture require further, more specific, analysis. Used in combination with GGT, CDT is thus a feasible marker for use in monitoring alcohol consumption in drivers needing to qualify for the restoration of their licences.

Adult↗
PubMed1998

The in vitro effect of lithocholic acid on the polymerization properties of PiZ alpha-1-antitrypsin.

We describe here an in vitro effect of lithocholic acid (LA), a secondary, hydrophobic bile acid, on the rate of polymerization of mutant, Z and wild-type, M alpha-1-antitrypsin (AAT). Using thioflavine T fluorescence and turbidity assays we demonstrated that the rate of aggregation for the Z AAT in the presence of LA at a molar ratio of 1:5 AAT to LA, in Tris-buffered saline, pH 7.4, is at least twice that of the Z protein alone or the M variant with and without LA. Also, Z AAT incubated for 48 h at room temperature had more than 50% diminished antielastase activity, while M AAT had only a 25% reduction in activity. Analysis of the AAT and AAT-LA samples after cleavage with pancreatic elastase by SDS-PAGE 10% gels showed that interaction between Z or M AAT and LA abolishes their ability to form SDS stable complexes with an enzyme and both of these forms of AAT showed elastase substrate behavior. Furthermore, Z as well as M AAT incubated with LA at 41 degrees C and cleaved with elastase showed only 80 to 60% increased thermal stability compared to 100% stabilization for the cleaved AAT alone in the absence of LA. These observations suggest that a rearrangement of the AAT molecule as a result of interactions with LA increases aggregation of AAT and diminishes its inhibitory activity.

Benzothiazoles↗
PubMed1998

Immediate assessment of HbA1c under field conditions in Tanzania.

In Tanzania, assessment of blood glucose is the most frequently used method for evaluating glycaemic control in diabetic patients. The patients' metabolic control is often poor and the determination of glycated haemoglobin (HbA1c) for long-term control could be a valuable tool to better manage the treatment. The aim of this study was to determine whether an immediate assessment method for HbA1c (DCA 2000 analyzer) gives reliable results in the warm and moist climate of east Africa. The study was performed in two parts. One equipment test in Sweden where blood samples from 65 diabetic patients were analysed in a DCA 2000 kept at room temperature and in another kept in a climate chamber. The samples were also analysed with HPLC as a reference method. In the second part HbA1c was analysed in 159 Tanzanian diabetic patients with a DCA 2000 and with HPLC combined with a filter paper technique (HbA1c via Post). The study showed that the DCA 2000 gives reliable results at 85% humidity and a temperature not exceeding +31 degrees C. The correlation with the HPLC analysis varied between 0.94 and 0.98. The conclusion is that the DCA 2000 analyzer can be used in Tanzania during the winter but has to be placed in an air-conditioned room if the temperature exceeds +31 degrees C.

Adult↗
PubMed1998

Assessment of sex hormones and bone mineral density in relation to occurrence of fracture in men: a prospective population-based study.

Patients with fragility fractures have low bone mineral density (BMD)--this statement is supported mainly by data on women. In this study, including only men, the objectives were to determine whether a decline in BMD alone or in combination with data on male sex hormones and skinfold thickness could be of value in predicting forthcoming fractures. We also wanted to find out whether high consumers of alcohol can be identified by measuring BMDs and male sex hormones. A prospective, population-based study was performed in the city of Malmö, Sweden. 242 men were randomly selected; all were of Scandinavian ethnic background, and were aged 50, 60, 70, and 80 years. Forearm BMD, testosterone, sex-hormone-binding globulin (SHBG), and skinfold thickness were analyzed. In addition, alcohol consumption and carbohydrate-deficient transferrin (CDT)--a marker of alcohol abuse--were analyzed. The study group was followed prospectively for 7 years and all fractures sustained were recorded. Prospectively, for a 1 SD decrease in forearm BMD, the Cox proportional hazard model gave a relative risk (RR) of 1.75 with a 95% confidence interval of 1.08-2.83 for a forthcoming fracture and 3.88 (1.30-11.57) for a hip fracture. For a 1 SD change in skinfold thickness, measured on the dorsum of the hand, a RR of 1.69 (0.99-2.87) for a forthcoming fracture was found and the corresponding value for hip fracture was 2.34 (1.10-5.00). Testosterone and SHBG did not enhance fracture prediction. Abusers of alcohol had, retrospectively, significantly more fractures. Individuals with alcohol consumption rates in the highest quartile had significantly higher CDT levels, but we were unable to identify high consumers of alcohol by analyzing BMD or sex hormones. In this study we found that forearm BMD and skinfold thickness could be used in predicting forthcoming fractures in men.

Aged↗
PubMed1998

The frequency and severity of retinopathy are related to HbA1c values after, but not at, the diagnosis of NIDDM.

OBJECTIVES: To examine the relationship between previous glycaemic exposure and prevalence of retinopathy 8 years after diagnosis of diabetes in 58 islet cell antibodies (ICA)-negative noninsulin-dependent diabetes mellitus (NIDDM) patients and in a group of 14 ICA-positive 'NIDDM' and insulin-dependent diabetes mellitus (IDDM) patients. DESIGN AND METHODS: The Wisconsin retinopathy scale was used to assess the retinopathy which was graded into mild, moderate and severe nonproliferative diabetic retinopathy (NPDR), or proliferative retinopathy (PDR). The frequency and severity of retinopathy was related to HbA1c levels at diagnosis, and 3 and 5 years later. RESULTS: Thirty of the 58 ICA-negative NIDDM patients (52%) but only 2 of the 14 ICA-positive 'NIDDM' or IDDM patients (14%) had mild-moderate-severe NPDR 8 years after diagnosis (P = 0.02). None had PDR. Retinopathy 8 years after diagnosis in NIDDM (= 58 ICA-negative patients) was correlated with the degree of glycaemic control (HbA1c levels) at 3 and 5 years after diagnosis, but not to HbA1c levels at diagnosis. The relative risk for a higher average HbA1c (per percentage) at 3 and 5 years was 1.56 for any retinopathy vs. no retinopathy (95% confidence interval 1.1-2.2; P = 0.01) and 1.68 for moderate to severe NPDR in comparison with no DR and mild NPDR (95% confidence interval 1.0-2.8; P = 0.04). CONCLUSIONS: Retinopathy after 8 years of diabetes in NIDDM patients was associated with impaired glycaemic control during previous years but not with glycaemic control at baseline. Good glycaemic control may prevent retinopathy in patients with NIDDM.

Adolescent↗
PubMed1998

Preparation of a candidate primary reference material for the international standardisation of HbA1c determinations.

We prepared a candidate primary reference material for the forthcoming international standardisation of beta-N-terminal glycated hemoglobin A measurements. It consists of well-defined mixtures of purified beta-N-terminal glycated hemoglobin A and non-glycated hemoglobin A. First, beta-N-terminal glycated hemoglobin A and non-glycated hemoglobin A were isolated, purified to homogeneity, and characterised. The techniques used were cation exchange and affinity chromatography for the purification, and high performance liquid chromatography, capillary isoelectric focusing, electrospray ionisation mass spectrometry, and peptide mapping for the characterisation. Hemoglobins from blood of healthy, non-diabetic volunteers were obtained with a purity of > 99.5% for non-glycated hemoglobin A and of > 98.5% for beta-N-terminal glycated hemoglobin A. However, results from peptide mapping indicate that the beta-N-terminal glycated hemoglobin A preparations still contain some non-beta-N-terminal glycated hemoglobins, co-eluting with beta-N-terminal glycated hemoglobin A. The exact content of beta-N-terminal glycated hemoglobin A in these preparations could be determined by a procedure consisting of standard addition, enzymatic cleavage and quantification of the resulting beta-N-terminal peptides to be in the range from 95-97.5%. Since the beta-N-terminal glycated hemoglobin A and non-glycated hemoglobin A content could be exactly determined in the materials prepared, mixtures of both components could be successfully used to calibrate the candidate reference methods.

Chromatography, Affinity↗
PubMed1997

Candidate reference methods for hemoglobin A1c based on peptide mapping.

A reference method that specifically measures hemoglobin (Hb) A1c is an essential part of the reference system for the international standardization of Hb A1c/glycohemoglobin. We have developed a new method for quantification, based on the specific N-terminal residue of the hemoglobin beta-chains. Enzymatic cleavage of the intact hemoglobin molecule with endoproteinase Glu-C has been optimized to obtain the beta-N-terminal hexapeptides of Hb A1c and Hb A0. These peptides have been separated by reversed-phase HPLC and quantitated by electrospray ionization-mass spectrometry (method A) or by capillary electrophoresis (method B). With these peptides and hyphenated separation techniques, it has been possible to overcome the insufficient resolution of currently used protein separation systems for Hb A1c.

Chromatography, High Pressure Liquid↗
PubMed1996

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 degrees C (room temperature) or at 4-6 degrees C (refrigerator) for 10 days as well as at -70 degrees 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.

Blood Specimen Collection↗
PubMed1995

Carbohydrate composition of serum transferrin isoforms from patients with high alcohol consumption.

Normal human serum transferrin is present in several isoforms, due to differences in glycosylation. Transferrin has two potential glycosylation sites, both normally occupied by oligosaccharide chains. Two of the transferrin isoforms, called carbohydrate deficient transferrin, are specifically increased in patients with high alcohol consumption. In this study, five isoforms of transferrin were isolated from patients with high alcohol consumption. N-linked glycans were released by N-glycosidase digestion and were radioactively labeled by NaB3H4 reduction. The purified oligosaccharides were analyzed by high-pH anion-exchange chromatography, and the carbohydrate composition of each individual transferrin isoform was determined. The carbohydrate deficient transferrin isoforms were found to lack one or both of their entire carbohydrate chains.

Alcohol Drinking↗
PubMed1995

Clinical course and cystine stone formation during tiopronin treatment.

The formation of stones in patients with cystinuria can be counteracted by reducing the urinary concentration of cystine and by increasing its solubility. Thirty-one patients with homozygous cystinuria and treated with tiopronin (2-mercaptopropionylglycine) were followed for between 0.4 and 12 years (median 8.8). With the aim of avoiding cystine concentrations above 1200 mumol/l, the daily dose varied between 500 and 3000 mg (median 1500). The therapeutic effect was evaluated from the clinical symptoms and repeated radiographic examinations. The rate of stone formation during the treatment period was reduced by 60% in comparison with the pretreatment period (P < 0.001). The frequency of active stone removal was reduced by 72% (P < 0.05). The formation of new stones was associated with a higher cystine concentration than was the case during periods when stone formation and stone growth were excluded (P < 0.05). The probability of new stone formation increased with increasing concentrations of cystine up to 1100 mumol/l, but stone formation was not accentuated above 1200 mumol/l. There was no significant relationship between the 24 h excretion of cystine and stone formation. It is concluded that the formation of cystine stones can be efficiently counteracted during treatment with tiopronin, guided by analysis of the concentration of urinary cystine.

Adolescent↗
PubMed1995

Measurement of diurnal variations in urinary cystine saturation.

In an attempt to improve the diagnostic value of urine analysis in patients with homozygous cystinuria, we studied the diurnal variation in urine composition. A simplified estimate of the ion-activity product of cystine was used to increase the probability of identifying patients with a particular risk of stone formation. Eight 6-h urine samples were collected during two 24-h periods. The highest urinary excretion of cystine was recorded between 1200 and 1800 hours and the lowest between 0000 and 0600 hours, whereas the urinary cystine concentration was highest between 0000 and 0006 hours and lowest between 1200 and 1800 hours. The approximate ion-activity product of cystine had a maximal level between 0000 and 0600 hours but a minimal level between 0600 and 1200 hours. The differences between different periods were numerically more pronounced in terms of the ion-activity product of cystine than in terms of concentration. The peak concentrations of cystine in 6-h samples were about 90% higher than the corresponding concentrations in 24-h urine samples. It is concluded that the analysis of cystine in 6-h urine samples reveals transient episodes of cystine supersaturation that otherwise will remain undetected. Further studies are, however, needed to establish its usefulness in clinical practice.

Adult↗
PubMed1995

Urinary excretion of free cystine and the tiopronin-cysteine-mixed disulfide during long term tiopronin treatment of cystinuria.

We report the results of a biochemical evaluation of long-term treatment of cystinuria with the SH compound tiopronin (2-mercaptopropionylglycine). The effects of tiopronin were studied by monitoring the urinary excretion of free cysteine and the mixed disulfide between tiopronin and cysteine. Thirty-one patients with homozygous cystinuria were treated with tiopronin for 0.4-12 years (mean 7.8 years). The urinary concentration of free cysteine was used to adjust the tiopronin dose. In 28 of the 31 patients a mean urinary cystine concentration of less than 1,200 mumol/1(288 mg/l) was achieved with the final dose. The final daily doses of tiopronin ranged from 250 mg (1.5 mmol) to 3,000 mg (18.4 mmol; mean 1,540 mg; 9.4 mmol). In a majority of the patients the treatment reduced the 24-hour urinary free cystine excretion effectively, on average by 0.61 mumol (0.15 mg)/mg of tiopronin administered. No changes in the efficacy of tiopronin over time were observed, and the frequency of adverse effects was acceptable. To evaluate the effects of tiopronin on the metabolism of cystine we calculated the total urinary excretion of cystine as the sum of free cystine and the amount of cystine corresponding to the cysteine content of the tiopronin-cysteine disulfide. At low doses of tiopronin there was an increase in urinary excretion of the mixed disulfide as well as of total cystine. Monitoring urinary cystine concentration is necessary to achieve adequate individualized doses of tiopronin. Assessment of the mixed tiopronin-cysteine disulfide and the urinary excretion of total cystine shows that tiopronin may interfere with cystine metabolism in a more complex way than through a simple disulfide exchange reaction with urinary cystine.

Adolescent↗
PubMed1995

The effect of sodium intake on cystinuria with and without tiopronin treatment.

As with many other amino acids the transport of cystine across the tubular epithelium is coupled to a parallel transport of sodium. We have studied the effect of a sodium-restricted diet on the urinary excretion of cystine in 13 patients with cystinuria, 7 of whom were treated with the SH compound tiopronin (2-mercaptopropionylglycine). Five of the patients with tiopronin and 5 without were also given sodium bicarbonate. The patients were instructed to follow a sodium-restricted diet during three periods of 2 weeks each. Four levels of sodium intake were obtained including the preexperimental unrestricted diet. The average 24-hour excretion of free cystine increased by 3.1 mumol (0.75 mg) for each millimole increase in urinary sodium (p < 0.001). There was a greater sodium-related increase in excretion of cystine among patients without tiopronin treatment compared with the group with tiopronin (p < 0.01). Withdrawal of sodium bicarbonate resulted in a decrease in the 24-hour cystine excretion (p < 0.05). In the patients treated with tiopronin the excretion of the mixed disulfide increased with increasing urinary sodium (p < 0.05) suggesting a sodium-dependent active tubular reabsorption of this compound as well. We conclude that in spite of a defective proximal tubular reabsorption of cystine in cystinuria the reabsorption can be increased by restricting the intake of sodium. This effect of sodium may have clinical consequences for some cystinuric patients.

Adolescent↗
PubMed1994

Improved method for analysis of glycated haemoglobin by ion exchange chromatography.

The Pharmacia Mono S column for glycated haemoglobin (HbA1c) was compared with Mono S HR 5/5 and three other cation exchange columns to optimize analysis of HbA1c. This column allows a significant decrease in separation time, resulting in a sample throughput of 12 samples per hour. The choice of parameters for integration of peak areas in the chromatograms is very important for reproducible results. Since pure calibrators of HbA1c are not available, the relative contribution of HbA1c to the total amount of haemoglobin is calculated. We have compared valley-to-valley integration with baseline integration to assess reproducibility. Valley-to-valley integration significantly enhances the reproducibility of the method and is therefore preferable for routine analyses of HbA1c.

Blood Proteins↗
PubMed1993

Rare beta chain hemoglobin variants found in Swedish patients during HBA1c analysis.

Here we report the occurrence of five different beta chain hemoglobin variants not previously described in Sweden. The variants were found during quantification of HbA1c using ion exchange high performance liquid chromatography (HPLC) or isoelectrofocusing. Samples were examined either at protein level by separation of globin chains on C8 reversed phase HPLC, digestion with trypsin or lysylendopeptidase and separation of peptides by C18 reversed phase HPLC, or at DNA level by direct nucleotide sequencing of double-stranded DNA fragments amplified from exon 1 + 2 of the beta-globin gene. The variants were: Hb Raleigh [beta 1 (NA1)Val-->Ac-Ala], Hb J-Baltimore [beta 16(A13)Gly-->Asp], Hb Tacoma [beta 30(B12)Arg-->Ser], Hb K-Ibadan [beta 46(CD5)Gly-->Glu], and Hb Fukuyama [beta 77(EF1)His-->Tyr]. Hb Tacoma, Hb K-Ibadan, and Hb Fukuyama were slightly unstable in the isopropanol test, but no signs of hemolysis were found in the patients who all had normal hematological findings.

Adolescent↗
PubMed1993

Europium-labeled oligonucleotides to detect point mutations: application to PIZ alpha 1-antitrypsin deficiency.

We describe a novel assay for detection of point mutations. The method combines the specificity and sensitivity of the polymerase chain reaction (PCR) and allele-specific oligonucleotides (ASO) with highly sensitive time-resolved fluorometry. ASO probes differing by a single base substitution and labeled with europium (Eu) chelates were hybridized in solution simultaneously with a biotinylated oligomer to a PCR-amplified nucleic acid fragment. The hybrids formed were then collected onto streptavidin-coated microtitration wells. Subsequently, the hybrids were washed under stringent conditions and the remaining ASO probe was measured in a time-resolved fluorometer. We discuss the strategy underlying the design of the Eu-labeled ASO probes for the solution hybridization assay. The method was applied to the detection of the Z-mutation in the alpha 1-antitrypsin gene. Evaluation of whole-blood samples spotted on Guthrie cards demonstrated successful accuracy of the method.

Base Sequence↗
PubMed1993

Carbohydrate-deficient transferrin quantified by HPLC to determine heavy consumption of alcohol.

We developed a new fully automated ion-exchange chromatographic method for quantitating carbohydrate-deficient transferrin (CDT) on a Mono Q column. Quantitation relies on the selective absorbance of the iron-transferrin complex at 460 nm. Transferrin isoforms deficient in sialic acid, with pIs 5.7 and 5.9, can easily be separated and quantitated as a percentage of the total transferrin. This method has been applied to samples from teetotalers, occasional drinkers, patients with recent heavy alcohol consumption, and patients during detoxification. The sensitivity of the method was 55% in patients reporting 40-70 g daily ethanol consumption and nearly 100% in heavily intoxicated patients (70-500 g daily consumption). The half-life of the dominating pI 5.7 isoform in this group was 9.5 (+/- 1) days during detoxification. A CDT value > 0.8% is a highly specific marker for alcohol abuse and is greatly superior to other currently available biological markers.

Adult↗