The haptoglobin 2-2 phenotype affects serum markers of iron status in healthy males.

BACKGROUND: Human iron status is influenced by environmental and genetic factors. We hypothesized that the genetic polymorphism of haptoglobin (Hp), a hemoglobin-binding plasma protein, could affect iron status. METHODS: Reference values of serum iron status markers were compared according to Hp phenotypes (Hp 1-1, Hp 2-1, Hp 2-2; determined by starch gel electrophoresis) in 717 healthy adults. Iron storage was investigated in peripheral blood monocyte-macrophages by measuring cytosolic L- and H-ferritins and by in vitro uptake of radiolabeled ((125)I) hemoglobin-haptoglobin complexes. RESULTS: In males but not in females, the Hp 2-2 phenotype was associated with higher serum iron (P <0.05), transferrin saturation (P <0.05), and ferritin (P <0.01) concentrations than Hp 1-1 and 2-1, whereas soluble transferrin receptor concentrations were lower (P <0.05). Moreover, serum ferritin correlated with monocyte L-ferritin content (r = 0.699), which was also highest in the male Hp 2-2 subgroup (P <0.01). In vitro, monocyte-macrophages took up a small fraction of (125)I-labeled hemoglobin complexed to Hp 2-2 but not to Hp 1-1 or 2-1. CONCLUSIONS: The Hp 2-2 phenotype affects serum iron status markers in healthy males and is associated with higher L-ferritin concentrations in monocyte-macrophages because of a yet undescribed iron delocalization pathway, selectively occurring in Hp 2-2 subjects.

Difficulties in evaluating urinalysis following combined pancreas-kidney transplantation.

Combined pancreas-kidney transplantation has been introduced in the treatment of patients with type 1 diabetes and renal failure 20 years ago. By 1985 374 combined pancreas-kidney transplantations had been reported to the International Pancreas Transplant Registries. Surgical drainage of the transplanted exocrine pancreas into the urinary bladder solves most of the postoperative problems encountered with the exocrine secretions. Furthermore, monitoring of pancreatic enzyme (amylase) activity in urine has been shown to be useful in diagnosis of rejection of the pancreatic graft. However, little attention has been paid to the biochemical consequences of high activities of proteolytic pancreatic enzymes on the determination of urinary proteins. The present case illustrates the difficulties in interpreting proteinuria in patients with combined pancreas-renal transplant with pancreaticocystostomia. In the propositus, interpretation of the urinary protein electrophoresis is hampered by the presence of pancreatic juice proteins and peptides originating from digestion of proteins by activated pancreatic enzymes. Results of immunochemically determined marker proteins ([micro]albumin, transferrin, beta 2-microglobulin) are unreliable due to digestion by pancreatic enzymes.

Effect of haptoglobin on the metabolism of vitamin C.

Haptoglobin is a hemoglobin-binding antioxidant showing a genetic polymorphism with three types: Hp 1-1, Hp 2-1, and Hp 2-2. The Hp 2-2 type has been associated with an increased risk of atherosclerosis. We investigated vitamin C metabolism in vivo and in vitro according to haptoglobin type in a study group of 135 healthy volunteers. Serum vitamin C concentrations were associated with haptoglobin type, showing lowest values in serum from Hp 2-2 subjects (P < 0.01). Renal threshold for L-ascorbic acid was within the normal range and metabolization to oxalate was not different among haptoglobin-type groups. Serum concentrations of other endogenous antioxidants (uric acid, bilirubin, albumin, ceruloplasmin, and total antioxidative status) were not different among haptoglobin-type groups. In vitro experiments showed a lower stability of L-ascorbic acid in blood from subjects with the Hp 2-2 type (P < 0.01). L-Ascorbic acid depletion in vitro was inversely related to haptoglobin concentration (r = -0.738). The results of this study indicate a higher rate of L-ascorbic acid oxidation in Hp 2-2 carriers because they have less protection against hemoglobin-iron driven peroxidation.

Evolution of haptoglobin concentration in serum during the early phase of acute myocardial infarction.

Haptoglobin (Hp) is a haemoglobin-binding acute phase protein with three genetic types: Hp 1-1, Hp 2-1, Hp 2-2. We investigated 45 patients during the first 48 hours of acute myocardial infarction, and studied determinant factors and clinical correlates. Upon hospital admission, serum haptoglobin concentration was increased (1.95 +/- 0.94 g/l, mean +/- SD, P < 0.001) versus the reference population (0.97 +/- 0.46 g/l, n = 107), independent of haptoglobin type: 1.84 +/- 0.64 g/l (Hp 1-1, n = 11) (P < 0.01), 1.98 +/- 0.79 g/l (Hp 2-1, n = 25) (P < 0.001), 1.98 +/- 1.58 g/l (Hp 2-2, n = 9) (P < 0.001). Moreover, during the first hours of hospitalization, a temporal lowering of haptoglobin was observed suggesting acute haemolysis, independent of the haptoglobin type. Minimal serum haptoglobin was reached 9.6 +/- 5.8 hours after admission. The amplitude of the haptoglobin decrease correlated with initial serum haptoglobin (r = 0.78) and was more pronounced (P < 0.05) in men (0.53 +/- 0.57 g/l) than in women (0.18 +/- 0.17 g/l). Decrease of serum haptoglobin did not correlate with infarct size (based on creatine kinase-MB release). Out of the other acute phase proteins measured upon admission, only C-reactive protein was significantly increased (P < 0.05). During the next 36 hours, haptoglobin increased as a result of the acute phase response to myocardial injury. Our findings suggest that acute myocardial infarction is also preceded by an acute phase response, characterized by an initial high haptoglobin and followed by a temporal haptoglobin decrease due to haemolysis.

Quantitative nephelometric assay for determining alpha-foetoprotein evaluated.

A recently introduced automated nephelometric immunoassay involving shell/core particles for determination of alpha-foetoprotein in serum and amniotic fluid was evaluated with the Behring Nephelometer analyser II. Method stability was good: reconstituted reagents and calibration curve were stable for at least one week. The intra-assay CV varied between 2.3% and 4.0%. The inter-assay CV varied between 3.5% and 4.6%. Samples with alpha-foetoprotein concentrations up to 273000 micrograms/l were analysed without high-dose "hook" effect after automatic dilution. No significant interference from haemoglobin, bilirubin, rheumatoid factors, or human anti-mouse antibodies was detected up to concentrations of 0.15 mmol/l haemoglobin, 268 mumol/l bilirubin, 470 int, units/l rheumatoid factor and a titre of 1/1000 human anti-mouse antibodies. Interference due to triacylglycerols depended on the size of triacylglycerol containing particles: for VLDL, interference did not occur up to triacylglycerol levels of 6.0 mmol/l, for chylomicrons interference was already noted at triacylglycerol levels of 1.0 mmol/l. Correlation with a commercial RIA (Kabi Pharmacia) was excellent both for serum (n = 65) and amniotic fluid (n = 100). The effect of the molecular variation of the carbohydrate moiety of alpha-foetoprotein on the test results was studied using concanavalin A affinity chromatography. The detection of both concanavalin A-reactive and concanavalin A-non-reactive alpha-foetoprotein was equivalent by both methods. Multimeric forms of alpha-foetoprotein were prepared by gel permeation chromatography. The effect of autopolymerization of alpha-foetoprotein on the nephelometric determination of alpha-foetoprotein was negligible. We conclude that latex-enhanced immunonephelometry is a rapid, practical, and reliable method for measuring alpha-foetoprotein in serum and amniotic fluid.

Treatment of crack-cocaine-induced compulsive behavior with trazodone.

Foraging is a compulsive behavior of searching for pieces of crack cocaine that the individual believes might have been accidentally misplaced. Three clinical cases of compulsive foraging behavior associated with crack cocaine are described. Due to the development of side effects secondary to the antidepressant desipramine, the patients were switched to the antidepressant trazodone. The use of trazodone led to remission of the foraging behavior. The authors hypothesize this remission was due to trazodone serotonin reuptake inhibitory action. In all three cases, the patients did not relapse into abusing crack cocaine.

Individualized treatment for alcohol withdrawal. A randomized double-blind controlled trial.

OBJECTIVE: To assess the effect of an individualized treatment regimen on the intensity and duration of medication treatment for alcohol withdrawal. DESIGN: A randomized double-blind, controlled trial. SETTING: An inpatient detoxification unit in a Veterans Affairs medical center. PATIENTS: One hundred one patients admitted for the treatment of alcohol withdrawal who could give informed consent and had no history of seizures or medication use that might alter the clinical course of withdrawal. INTERVENTION: Patients were randomized to either a standard course of chlordiazepoxide four times daily with additional medication as needed (fixed-schedule therapy) or to a treatment regimen that provided chlordiazepoxide only in response to the development of the signs and symptoms of alcohol withdrawal (symptom-triggered therapy). The need for administration of "as-needed" medication was determined using a validated measure of the severity of alcohol withdrawal. MAIN OUTCOME MEASURES: Duration of medication treatment and total chlordiazepoxide administered. RESULTS: The median duration of treatment in the symptom-triggered group was 9 hours, compared with 68 hours in the fixed-schedule group (P < .001). The symptom-triggered group received 100 mg of chlordiazepoxide, and the fixed-schedule group received 425 mg (P < .001). There were no significant differences in the severity of withdrawal during treatment or in the incidence of seizures or delirium tremens. CONCLUSIONS: Symptom-triggered therapy individualizes treatment, decreases both treatment duration and the amount of benzodiazepine used, and is as efficacious as standard fixed-schedule therapy for alcohol withdrawal.