The aminothiol redox status in haemodialysis patients does not improve with folate therapy.

BACKGROUND: Patients on haemodialysis suffer from high cardiovascular morbidity and mortality, and oxidative stress may play a role in the pathophysiology of cardiovascular disease in these patients. Hyperhomocysteinemia is common in dialysis patients and may have pro-oxidant effects. Moreover, the redox status of the major plasma aminothiols (homocysteine [Hcy], cysteine and cysteinylglycine) may be regarded as a biomarker of oxidative stress. In the present study, we investigated the aminothiol redox status during a period of homocysteine-lowering therapy with folinic acid. MATERIAL AND METHODS: In the first part of the study, 32 stable patients receiving maintenance haemodialysis were compared with 32 reference subjects. In the second part, the patients were given folinic acid intravenously for 3 months. RESULTS: Before intervention with folinic acid, the patients had elevated concentrations of all redox species of Hcy. The aminothiol redox ratios were low. Folinic acid therapy lowered the concentrations of all Hcy redox species; however, the redox ratios did not improve. CONCLUSIONS: The low aminothiol redox ratios indicate the presence of oxidative stress in haemodialysis patients. Therapy with folinic acid lowered total Hcy concentrations, but did not improve the redox status. Thus, hyperhomocysteinemia appears to be of little importance in regard to the total level of oxidative stress in uraemia.

Homocysteine, malondialdehyde and endothelial markers in dialysis patients during low-dose folinic acid therapy.

OBJECTIVES: Haemodialysis patients have elevated levels of the atherogenic amino acid homocysteine. We wanted to assess the effects of small doses of intravenous folinic acid (the active form of folic acid) on some biochemical risk factors of cardiovascular disease. DESIGN: Longitudinal and open intervention study. SETTING: Two dialysis units in the County of Rogaland. SUBJECTS: All patients on maintenance haemodialysis were invited, and 32 of 35 patients gave their informed consent. INTERVENTIONS: After each dialysis session, the patients were given 1.0 mg of folinic acid intravenously thrice a week for a period of 3 months. Prior to and during the study, all patients were on maintenance supplementation with small doses of vitamins B1, B2, B3, B5, B6 and B12. MAIN OUTCOME MEASURES: Changes in the levels of (i) plasma total homocysteine (p-tHcy) and folate, (ii) circulating endothelium related proteins--markers of endothelial activation and (iii) serum malondialdehyde (S-MDA)--a marker of oxidative stress and lipid peroxidation. RESULTS: The p-tHcy levels were reduced by 37% (P < 0.0001), whilst the serum and erythrocyte folate levels increased by 95 and 104%, respectively (P < 0.0001 for both). The circulating levels of endothelium related cellular adhesion molecules and haemostatic factors remained high and unchanged, except the thrombomodulin (TM) levels increased (P = 0.0004). The high levels of S-MDA were reduced by 26% (P = 0.003). CONCLUSIONS: Low doses of folinic acid given intravenously to dialysis patients reduced their levels of p-tHcy and S-MDA and thus improved their cardiovascular risk profile. The concurrent increment in TM levels was unexpected and of unknown clinical significance.

Antiepileptic drugs as independent predictors of plasma total homocysteine levels.

Low folate levels have consistently been reported in patients with epilepsy on phenytoin (PHT), phenobarbital (PB) and primidone (PRD), while data on valproate (VPA) are conflicting. Furthermore, antiepileptic drugs (AEDs) may be associated with high levels of plasma total homocysteine (p-tHcy). Therefore, we have investigated the levels of p-tHcy, serum folate (S-FA) and erythrocyte folate (E-FA) in patients on PHT, PB and PRD (Group 1, n=21) and VPA (Group 2, n=24). Both groups had their own matched controls. Blood samples were drawn fasting and 6 h post methionine loading (6 h-PML). The Group 1 patients had fasting and 6 h-PML p-tHcy levels significantly higher than their controls (P=0.05 and <0.0001, respectively), and patients without dietary multivitamin supplementation (n=14), had lower fasting S-FA and E-FA levels than their controls (P=0.02 and 0.0003, respectively). The Group 2 patients had fasting and 6 h-PML levels of p-tHcy, S-FA and E-FA not different from their controls. In a multiple stepwise regression model comprising all subjects (n=90), the AEDs of Group 1 and the S-FA levels were independent predictors of p-tHcy levels. Thus, PHT, PB and PRD are associated with high p-tHcy and low folate levels, whereas VPA does not influence S-FA, E-FA and p-tHcy levels in adult patients.

Assessment of haematuria: automated urine flowmetry vs microscopy.

BACKGROUND: Microscopy of the urine sediment may be a useful method in the distinction between a glomerular and a non-glomerular source of urinary bleeding. However, microscopic techniques are time consuming and hampered by inter-observer variations. In the present study we have therefore compared bright-field microscopy with automated urine flowmetry (Sysmex UF-100), examining their ability to differentiate between glomerular and non-glomerular haematuria. METHODS: Fresh urine samples were obtained from 112 patients with a well-defined, single cause of a positive dipstick test. Their urine specimens were examined within 4 h in a blinded manner. Of them, 79 specimens had a positive dipstick for blood and thus could be evaluated for haematuria. RESULTS: The Sysmex UF-100 had a sensitivity and specificity of 0.83 and 0.94 respectively in detecting non-glomerular bleeding. The positive and negative predictive values were 0.95 and 0.78 respectively. The corresponding values of microscopy were 0.79 and 0.90 respectively, and 0.93 and 0.74 respectively. CONCLUSIONS: Automated flowmetry can be used in the distinction between glomerular and non-glomerular haematuria.

Folate, homocysteine and methionine loading in patients on carbamazepine.

OBJECTIVES: Some antiepileptic drugs (AEDs) are associated with low levels of serum (S-FA) and erythrocyte folate (E-FA) and high levels of plasma total homocysteine (p-tHcy). We have explored the concentrations of S-FA, E-FA and p-tHcy in patients on carbamazepine (CBZ). The methionine loading test was applied for better assessment of mildly impaired homocysteine metabolism. MATERIAL AND METHODS: The study comprised 42 adult patients on CBZ and 42 matched healthy controls. Blood samples were drawn prior to and 6 h post methionine loading (6 h-PML) (0.1 g/kg body weight). RESULTS: The patients on CBZ had significantly lower concentrations of fasting S-FA and E-FA than the controls (P=0.0004, P=0.003, respectively). Fasting and 6 h-PML p-tHcy concentrations were significantly higher in the patients than in the controls (P=0.03 and P=0.0001, respectively). The methionine loading test identified additional patients with hyperhomocysteinemia undetected by fasting p-tHcy. CONCLUSION: CBZ therapy may be associated with low folate and high p-tHcy levels.

[Hypokalemic pareses secondary to renal tubular acidosis]. / Hypokalemisk induserte pareser sekundaert til renal tubulaer acidose.

A 24 year old woman presented with flaccid paralysis, severe hypokalaemia and hyperchloremia, metabolic acidosis. Immunological tests and labial glandular biopsy indicated primary Sjögren's syndrome as the underlying cause of her distal renal tubular acidosis. The patient recovered after alkali and potassium substitution and was put on oral treatment with potassium citrate.

Homocysteine concentrations and methionine loading in patients on antiepileptic drugs.

OBJECTIVES: A few reports have shown elevated fasting total plasma homocysteine (tHcy) in patients taking antiepileptic drugs (AEDs). In this study we determined the influence of AEDs on plasma tHcy levels prior to and following methionine loading. MATERIAL AND METHODS: Thirty-four patients on different AEDs and 34 matched controls were recruited. Blood samples were drawn prior to and 6 h post-methionine loading (6h-PML). RESULTS: The patients on AEDs inducing the cytochrome P450 (carbamazepine, phenytoin, phenobarbital, primidone), had higher fasting and 6h-PML plasma tHcy concentrations than the controls (P = 0.01 and P<0.001). Patients on AED inhibiting the cytochrome P450 (valproate [VPA]), had lower 6h-PML p-tHcy concentrations than controls (P = 0.01). CONCLUSIONS: Our data indicate that not only fasting but also 6h-PML tHcy levels should be determined in order to identify hyperhomocysteinemia among patients on AEDs. Inducer AEDs seem to have an opposite effect than the inhibitor VPA on plasma tHcy, erythrocyte folate and serum folate levels.

Thrombotic microangiopathy in a patient with chronic myelogenous leukemia on hydroxyurea.

We describe the case of a 57-year-old woman with chronic myelogenous leukemia who was on hydroxyurea and developed a fatal thrombotic microangiopathy with renal, retinal and central nervous system involvement. There was no evidence of medullary or extramedullary leukemia transformation. Repeated examinations of the peripheral blood film revealed only minimal morphological changes of microangiopathic hemolysis. The diagnosis was made by postmortem examination of the kidneys, brain, meninges and retina. The underlying etiology may have been a paraneoplastic phenomenon of the chronic phase of CML or may have indicated the beginning of transformation to an accelerated phase. A late side effect of hydroxyurea therapy cannot be excluded.

Flow cytometry of urinary erythrocytes for evaluating the source of haematuria.

Morphological examinations of urinary erythrocytes can be of diagnostic help in the initial evaluation of haematuria. Dysmorphic red blood cells are known to indicate a glomerular origin of bleeding. Automated flow cytometry produces objective measurements, but is hampered by disturbing signals from urinary debris. The present study is based on both volumetry and densiometry of red blood cells by the Technicon H-1TM system. Urines from 63 patients with both low grade and macroscopic haematuria were examined. The test sensitivity for detecting a non-glomerular source of bleeding was 0.75 (specificity: 0.86). After excluding 20 samples with either a low red cell count or a density below 1005, the sensitivity rose to 0.93 with a corresponding specificity of 1.00. The present findings suggest that partial reinterpretation of the autoanalyser data will enhance the diagnostic power of flow cytometry. This method could be made suitable for routine clinical use.

[Pregnant diabetics. A retrospective study of pregnancy and labor in women with type 1 diabetes in Sør-Rogaland 1982-90]. / Gravide diabetikere. En retrospektiv undersøkelse av svangerskap og fødsel hos type 1-diabetikere i Sør-Rogaland 1982-90.

Foetal mortality and morbidity rates are higher among pregnant diabetics than in the general population of pregnant women. From 1982 to 1990, 59 pregnant diabetics were closely supervised by a dedicated outpatient team. Throughout the pregnancies the insulin demand increased, and metabolic control improved. 78 babies were born. The perinatal mortality rate was 3.9%. Major congenital anomalies occurred in 6.4%. The presence of maternal diabetic complications was associated with a higher rate of perinatal complications. The risk of anomalies and high birth weight increased with poor metabolic control. Diabetic women of childbearing age should therefore receive advice before any planned pregnancy.