Methylmalonic acid concentrations in serum of normal subjects: biological variability and effect of oral L-isoleucine loads before and after intramuscular administration of cobalamin

1990 ◽  
Vol 36 (7) ◽  
pp. 1295-1299 ◽  
Author(s):  
K Rasmussen ◽  
J Møller ◽  
K Ostergaard ◽  
M O Kristensen ◽  
J Jensen
Keyword(s):  
Methylmalonic Acid ◽  
Normal Subjects ◽  
Reference Interval ◽  
Cobalamin Deficiency ◽  
Intramuscular Administration ◽  
Significant Relation ◽  
Clinical Value ◽  
Individual Variations ◽  
Significant Difference ◽  
Before And After

Abstract The clinical value of measuring concentrations of methylmalonic acid in serum (S-MMA) as an aid in the diagnosis of cobalamin deficiency has recently aroused interest. In 58 healthy subjects, ages 40-68 years, we found a 0.95 reference interval of 0.05-0.37 mumol/L (mean 0.21, SD 0.094). In 33 of the subjects, who were studied further, day-to-day variation (SD) was 0.031 mumol/L. Intake of food had no effect. Weekly and three-monthly intra-individual variations were both 0.038 mumol/L. In all seven subjects with S-MMA greater than 0.30 mumol/L, the concentrations declined significantly after intramuscular administration of cobalamin. No significant difference was found between mean serum cobalamin concentrations in these seven and in the remaining subjects. We have also established the normal response of S-MMA to standardized oral loading of L-isoleucine: 100 mmol caused a significant average S-MMA increase of 0.072 mumol/L before cobalamin administration vs 0.013 mumol/L after cobalamin, without significant relation to initial S-MMA values. Our results provide a necessary background for interpretation of S-MMA measurements in clinical studies.

Solid-phase sample extraction for rapid determination of methylmalonic acid in serum and urine by a stable-isotope-dilution method.

1989 ◽  
Vol 35 (2) ◽  
pp. 260-264 ◽  
Author(s):  
K Rasmussen
Keyword(s):  
Methylmalonic Acid ◽  
Solid Phase ◽  
Rapid Determination ◽  
Current Method ◽  
Reference Interval ◽  
Cobalamin Deficiency ◽  
Isotope Dilution Method ◽  
Dilution Method ◽  
Selected Ion Monitoring

Abstract Methylmalonic acid concentrations are increased in serum in vitamin B12 (cobalamin) deficiency. Here I demonstrate the successful use of anion-exchange extraction for improving newly developed analytical procedures and describe well-documented, reliable performance of this method for rapid determination of methylmalonic acid. The sorbent counter ion is formate, and the elution solvent is formic acid. The dicyclohexyl derivative is measured by selected ion monitoring. For serum, the assay curve is linear from 0.026 to 200 mumol/L. The normal reference interval is 0.08 to 0.56 mumol/L. Added methylmalonic acid is accurately quantified. The sensitivity and the precision exceed those of the current method by three orders of magnitude. The total and within-day CVs are 4.6% to 7.9% and 2.6% to 4.7%, respectively. Similar figures were obtained for urine. This convenient method is useful for evaluation of cobalamin deficiency, especially in patients with normal or moderately depressed cobalamin concentrations in serum.

Aminophylline and human diaphragm strength in vivo

1990 ◽  
Vol 68 (6) ◽  
pp. 2591-2596 ◽  
Author(s):  
R. D. Levy ◽  
S. Nava ◽  
L. Gibbons ◽  
F. Bellemare
Keyword(s):  
Motor Units ◽  
Normal Subjects ◽  
Acute Administration ◽  
Transdiaphragmatic Pressure ◽  
Gastric Pressure ◽  
Significant Difference ◽  
Before And After ◽  
Normal Human ◽  
Twitch Characteristics

The transdiaphragmatic pressure (Pdi) twitch response to single shocks from supramaximal bilateral phrenic nerve stimulation was studied before and after acute intravenous infusions of aminophylline [14.9 +/- 3.1 (SD) micrograms/ml] in nine normal subjects. Stimulation was performed with subjects in the sitting position against an occluded airway from end expiration. Baseline gastric pressure and abdominal and rib cage configuration were kept constant. There was no significant difference in peak twitch Pdi from the relaxed diaphragm between control (38.8 +/- 3.3 cmH2O) and aminophylline (40.2 +/- 5.2 cmH2O) experiments. Other twitch characteristics including contraction time, half-relaxation time, and maximum relaxation rate were also unchanged. The Pdi-twitch amplitude at different levels of voluntary Pdi was measured with the twitch occlusion technique, and this relationship was found to be similar under control conditions and after aminophylline. With this technique, maximum Pdi (Pdimax) was calculated as the Pdi at which stimulation would result in no Pdi twitch because all motor units are already maximally activated. No significant change was found in mean calculated Pdimax between control (146.9 +/- 27.0 cmH2O) and aminophylline (149.2 +/- 26.0 cmH2O) experiments. We conclude from this study that the acute administration of aminophylline at therapeutic concentrations does not significantly affect contractility or maximum strength of the normal human diaphragm in vivo.

scholarly journals Prevalence of Psychological Disorders in Patients with Alopecia Areata in Comparison with Normal Subjects

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Shahin Aghaei ◽  
Nasrin Saki ◽  
Ehsan Daneshmand ◽  
Bahare Kardeh
Keyword(s):  
Alopecia Areata ◽  
Psychological Disorders ◽  
Normal Subjects ◽  
Control Group ◽  
Case Group ◽  
Eysenck Personality Questionnaire ◽  
Significant Relation ◽  
Significant Difference ◽  
Prevalence Of Depression ◽  
And Control

Alopecia areata is a chronic disease with a great impact on the patient’s quality of life. In this study we reviewed the frequency of psychological disorders in patients with alopecia areata in comparison to a control group. We enrolled 40 patients with alopecia areata and a 40-volunteer random age-sex matched control group. The study is based on anxiety and Beck Depression Inventory (BDI) and the Eysenck Personality Questionnaire (EPQ). Analytical evaluation was done by Mann-Whitney, Kruskal Wallis, and t-tests. There was a significant difference between the case and control group regarding the prevalence of depression (P value = 0.008), anxiety (P value = 0.003), and neuroticism (P value = 0.05). There was no significant differences regarding extraversion (P value = 0.249), psychosis (P value = 0.147), and lying (P value = 0.899) between the two groups. In alopecia areata involving the head, there was a significant relation only between neuroticism (P value = 0.045) and lying (P value = 0.005). The facial involvement had a significant relation with depression (P value = 0.020), anxiety (P value = 0.019), and neuroticism (P value = 0.029). The frequency of psychological disorders in the case group is significantly greater than the control group.

scholarly journals Clinical spectrum and diagnosis of cobalamin deficiency [see comments]

Blood ◽  
1990 ◽  
Vol 76 (5) ◽  
pp. 871-881 ◽  
Author(s):  
SP Stabler ◽  
RH Allen ◽  
DG Savage ◽  
J Lindenbaum
Keyword(s):  
Cell Volume ◽  
Peripheral Blood ◽  
Methylmalonic Acid ◽  
Peripheral Blood Smear ◽  
Normal Subjects ◽  
Lactic Dehydrogenase ◽  
Serum Levels ◽  
Cobalamin Deficiency ◽  
Mean Cell Volume ◽  
Total Homocysteine

To better estimate how frequently patients with low serum cobalamin (Cbl) levels in current clinical practice are truly deficient in Cbl and to determine the incidence of atypical or nonclassic presentations of Cbl deficiency, we prospectively studied 300 unselected consecutive patients with serum Cbl concentrations less than 200 pg/mL seen at two medical centers over a 2-year period. Baseline hematologic, neuropsychiatric, and biochemical measurements were obtained, followed by a course of parenteral Cbl therapy and reassessment. A response to Cbl therapy was defined as one or more of the following: (1) an increase in hematocrit of 0.05 or more; (2) a decrease in mean cell volume of 5 fL or more; (3) a clearing of hypersegmented neutrophilis and macroovalocytes from the peripheral blood smear; and (4) an unequivocal and prompt improvement of neuropsychiatric abnormalities. Of the 300 patients with serum Cbl levels less than 200 pg/mL, 86 had one or more responses to Cbl therapy and 59 had no response. In 155, insufficient data was available. In the Cbl-responsive patients, normal values were found for the following tests: hematocrit, 44%; mean cell volume less than or equal to 100 fL, 36%; white blood cell count, 84%; platelet count, 79%; serum lactic dehydrogenase, 43%; and serum bilirubin, 83%. Peripheral blood smears were nondiagnostic in 6% when reviewed by the investigators, but 33% as reported by routine laboratories. Serum Cbl levels in the 100 to 199 pg/mL range were present in 38%. Neuropsychiatric abnormalities were noted in 28%, often in the absence of anemia, macrocytosis, or both. Serum levels of methylmalonic acid and/or total homocysteine were elevated greater than 3 SDs above the mean for normal subjects in 94% of the Cbl-responsive patients. We conclude that Cbl deficiency should be considered and investigated in patients with unexplained hematologic or neuropsychiatric abnormalities of the kind seen in Cbl deficiency, even if anemia, an elevated mean cell volume, a marked depression of the serum Cbl, or other classic hematologic or biochemical abnormalities are lacking. Levels of serum methylmalonic acid and total homocysteine are useful as ancillary diagnostic tests in the diagnostis of Cbl deficiency.

scholarly journals Relative Folate Deficiency of Erythrocytes in Pernicious Anemia and its Correction with Cyanocobalamin

Blood ◽  
1964 ◽  
Vol 24 (5) ◽  
pp. 502-521 ◽  
Author(s):  
BERNARD A. COOPER ◽  
LOUIS LOWENSTEIN
Keyword(s):  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Significant Proportion ◽  
Normal Subjects ◽  
Folate Deficiency ◽  
Serum Folate ◽  
Erythroid Cells ◽  
Significant Difference ◽  
Before And After ◽  
Erythrocyte Folate

Abstract 1. A relationship has been observed between the serum and erythrocyte folate in normal subjects. 2. Patients with folate deficiency were more readily differentiated from normal subjects by determinations of serum folate activity than by determinations of erythrocyte folate activity. 3. In pernicious anemia in relapse, accumulation of serum folate and/or depletion of erythrocyte folate was observed in all patients, resulting in a disturbance of the normal relationship between the serum and erythrocyte folate activity. This altered relationship was corrected following the reticulocytosis induced by vitamin B12 therapy. 4. Patients receiving amethopterin therapy appear to incorporate the folate antagonist into maturing erythroid cells, since the erythroid cells so formed showed anti-bacterial activity for several weeks following the administration of the antagonist. 5. Preliminary fractionation of folate co-enzymes in erythroid cells of a patient with pernicious anemia before and after therapy revealed no significant difference in the distribution of the co-enzymes induced by therapy. A significant proportion of the folate activity of the erythroid cells was found in a fraction eluted from the DEAE column by sodium hydroxide. 6. The data presented are consistent with a direct effect of vitamin B12 on folate transport into the erythroblast.

Continuous subcutaneous octreotide infusion markedly suppresses IGF-I levels whilst only partially suppressing GH secretion in diabetics with retinopathy

1989 ◽  
Vol 120 (2) ◽  
pp. 187-194 ◽  
Author(s):  
S. L. Hyer ◽  
P. S. Sharp ◽  
R. A. Brooks ◽  
J. M. Burrin ◽  
E. M. Kohner
Keyword(s):  
Normal Subjects ◽  
High Plasma ◽  
Prolonged Treatment ◽  
Somatostatin Analogue ◽  
Clinical Value ◽  
Gh Secretion ◽  
Treatment Regimens ◽  
Igf I ◽  
Before And After ◽  
Long Acting

Abstract. The response to GH releasing hormone (GHRH 1–29) and 24-h serum GH and IGF-I levels were measured in 9 insulin-dependent diabetics with retinopathy and 6 normal volunteers before and after different treatment regimens with octreotide, a long-acting somatostatin analogue. Octreotide, 50 μg by sc injection, completely suppressed GHRH-stimulated GH release in both groups. Thrice daily sc injections for up to 20 weeks were associated with variable plasma octreotide levels and failed completely to suppress GH secretion in either the patients or the normal controls. Three days of continuous sc pump infusion (500 μg/24-h) resulted in consistently high plasma octreotide levels and completely suppressed 24-h GH in 4 normal subjects, whilst treatment for up to 16 weeks only partially suppressed GH levels in 6 patients (AUC mU · l−1 · h−1;h 209 ± 81 vs 121 ± 82; P=0.01). Mean ± sd IGF-I levels (μg/l) in the patients (but not controls) were suppressed into the hypopituitary range by median 6 weeks (range 2–16) pump administration (203 ± 62 vs 60 ± 25; P= 0.02). Pump treatment achieved total GH suppression in normal subjects; diabetics with retinopathy seem more resistant to the GH suppressing effects of the drug. However, the reduction of serum IGF-I with prolonged treatment may be of clinical value in arresting the progress of diabetic retinopathy.

PLASMA PROLACTIN LEVELS AFTER TRH AND CHLORPROMAZINE IN NORMAL SUBJECTS AND PATIENTS WITH IMPAIRED PITUITARY FUNCTION

1975 ◽  
Vol 79 (4) ◽  
pp. 663-676 ◽  
Author(s):  
G. Schwinn ◽  
A. von zur Mühlen ◽  
J. Köbberling ◽  
E. Halves ◽  
K. W. Wenzel ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Normal Subjects ◽  
The Other ◽  
Pituitary Function ◽  
Hormonal Contraceptives ◽  
Plasma Prolactin ◽  
Significant Difference ◽  
Before And After ◽  
Basal Plasma ◽  
Maximum Increment

ABSTRACT Basal plasma prolactin levels and values after stimulation with TRH and chlorpromazine respectively were measured. TRH tests were performed in 50 healthy subjects (25 women and 25 men). The basal prolactin levels and the maximum increment were found to be as follows in women 22.02 ng/ml ± 5.02 sem and 100.0 ng/ml ± 11.3 sem respectively, in men 16.62 ng/ml ± 2.46 sem and 45.26 ng/ml ± 5.70 sem respectively. The maximum prolactin increase after chlorpromazine in 6 men amounted to 64.77 ng/ml ± 8.28 sem respectively and in 12 women, 6 of them taking hormonal contraceptives, 81.0 ng/ml ± 16.53 sem. There was no significant difference between the 2 groups of women. The behaviour of plasma prolactin under stimulation in patients with impaired pituitary function was compared with the other trophic pituitary functions before therapy, in 7 patients before and after hypophysectomy and 15 patients only after therapy. In addition 6 patients with tumours adjacent to the pituitary and 3 women with Sheehan's syndrome were investigated. Plasma prolactin before and after stimulation was not pathologically changed in all cases. After surgery the prolactin levels were also normal in many patients. In most of them slight or marked elevation of prolactin levels were found. There was no good correlation between the trophic pituitary functions in most cases. It seems that prolactin measurement under stimulation conditions is the most sensitive indicator of a residual pituitary function.

scholarly journals Clinical spectrum and diagnosis of cobalamin deficiency [see comments]

Blood ◽  
1990 ◽  
Vol 76 (5) ◽  
pp. 871-881 ◽  
Author(s):  
SP Stabler ◽  
RH Allen ◽  
DG Savage ◽  
J Lindenbaum
Keyword(s):  
Cell Volume ◽  
Peripheral Blood ◽  
Methylmalonic Acid ◽  
Peripheral Blood Smear ◽  
Normal Subjects ◽  
Lactic Dehydrogenase ◽  
Serum Levels ◽  
Cobalamin Deficiency ◽  
Mean Cell Volume ◽  
Total Homocysteine

Abstract To better estimate how frequently patients with low serum cobalamin (Cbl) levels in current clinical practice are truly deficient in Cbl and to determine the incidence of atypical or nonclassic presentations of Cbl deficiency, we prospectively studied 300 unselected consecutive patients with serum Cbl concentrations less than 200 pg/mL seen at two medical centers over a 2-year period. Baseline hematologic, neuropsychiatric, and biochemical measurements were obtained, followed by a course of parenteral Cbl therapy and reassessment. A response to Cbl therapy was defined as one or more of the following: (1) an increase in hematocrit of 0.05 or more; (2) a decrease in mean cell volume of 5 fL or more; (3) a clearing of hypersegmented neutrophilis and macroovalocytes from the peripheral blood smear; and (4) an unequivocal and prompt improvement of neuropsychiatric abnormalities. Of the 300 patients with serum Cbl levels less than 200 pg/mL, 86 had one or more responses to Cbl therapy and 59 had no response. In 155, insufficient data was available. In the Cbl-responsive patients, normal values were found for the following tests: hematocrit, 44%; mean cell volume less than or equal to 100 fL, 36%; white blood cell count, 84%; platelet count, 79%; serum lactic dehydrogenase, 43%; and serum bilirubin, 83%. Peripheral blood smears were nondiagnostic in 6% when reviewed by the investigators, but 33% as reported by routine laboratories. Serum Cbl levels in the 100 to 199 pg/mL range were present in 38%. Neuropsychiatric abnormalities were noted in 28%, often in the absence of anemia, macrocytosis, or both. Serum levels of methylmalonic acid and/or total homocysteine were elevated greater than 3 SDs above the mean for normal subjects in 94% of the Cbl-responsive patients. We conclude that Cbl deficiency should be considered and investigated in patients with unexplained hematologic or neuropsychiatric abnormalities of the kind seen in Cbl deficiency, even if anemia, an elevated mean cell volume, a marked depression of the serum Cbl, or other classic hematologic or biochemical abnormalities are lacking. Levels of serum methylmalonic acid and total homocysteine are useful as ancillary diagnostic tests in the diagnostis of Cbl deficiency.

Studies on methylmalonic acid in humans. I. Concentrations in serum and urinary excretion in normal subjects after feeding and during fasting, and after loading with protein, fat, sugar, isoleucine, and valine.

1989 ◽  
Vol 35 (12) ◽  
pp. 2271-2276 ◽  
Author(s):  
K Rasmussen
Keyword(s):  
Urinary Excretion ◽  
Methylmalonic Acid ◽  
Vitamin B12 Deficiency ◽  
Normal Subjects ◽  
Cobalamin Deficiency ◽  
Absolute Amount ◽  
Ambulatory Patients ◽  
B12 Deficiency ◽  
First Time

Abstract Determination of methylmalonic acid (MMA) in serum or urine for evaluation of tissue cobalamin (vitamin B12) deficiency is becoming an important diagnostic procedure. Here I present the first investigation of dietary influence on concentrations of MMA in serum and urine. Everyday meals caused an increase in urinary excretion, whereas the concentration in serum was not increased significantly. It is difficult to prime the accumulation of MMA in normal subjects by stressing the metabolic pathway; after loading subjects with 100 mmol of isoleucine or valine, the absolute amount of MMA excreted increased by only about 3 mumol. Its concentration in serum tended to decrease and its urinary excretion declined after lack of protein intake for more than 15 h. Although a linear relationship was demonstrated, for the first time, between concentrations in serum and urinary excretion, my results indicate that patients with early evidence of cobalamin deficiency and normal subjects may best be differentiated by measurements in serum, especially in the case of nonfasting (i.e., ambulatory) patients.

Effect of Peritoneal Dialysis and a Single Hemodialysis on Erythrocyte Membrane Atpase Activity of Uremic Subjects

1985 ◽  
Vol 5 (1) ◽  
pp. 31-32 ◽  
Author(s):  
Ozdogu Hakan ◽  
Gurcay Ali ◽  
Akoglu Tevfik ◽  
Akoglu Emel
Keyword(s):  
Peritoneal Dialysis ◽  
Normal Subjects ◽  
Acute Effect ◽  
Clinical Findings ◽  
Control Group ◽  
Significant Difference ◽  
Before And After ◽  
The Status ◽  
Unknown Structure ◽  
Comparison Of The Results

In this study erythrocytic A TPase activities were studied in 21 patients before and after six hours of hemodialysis. In another group of 20 patients A TPase activities were also studied before and after 48 72 hours of peritoneal dialysis. As a control group 20 healthy normal subjects were used. Comparison of the results revealed that all three (Na+/k+, Mg++, Ca++/Mg++) ATPase activities were lower in the chronic renal failure patients than normal controls (p < 0.001). Both peritoneal and hemodialysis increased significantly all three A TPase activities. When peritoneal and hemodialysis results were compared no significant difference was noted. It is concluded that the increase in A TPase activites observed by both dialysis methods is due to removal from the plasma of substances which are responsible for the decrease in A TPase activities before dialysis. In uremia numerous substances alone or together have been held responsible for various clinical findings. In addition some other metabolic wastes of unknown structure act upon important enzyme systems resulting to an altered cellular function. A TPase enzymes are a group of enzymes responsible for the maintenance of the ionic and osmotic balance of the cells. In this study we studied the status of these enzymes in ESRD patients undergoing dialysis and also the acute effect of peritoneal dialysis and hemodialysis on them.

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