[Decreased quality of clinical chemistry education for physicians].
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Chemistry, Clinical↗
Biomedical subjects
G Lindstedt
Publications and source records attributed to G Lindstedt.
[Increased value of TSH should always be investigated. Risk of incorrect treatment when the diagnosis is wrong].
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Antibodies↗
Determinants of bone loss in patients with Kock ileal urinary reservoir.
The purpose of the present study was to determine the change in bone mineral density (BMD) measured with dual energy X-ray absorptiometry (DXA) in patients with Kock reservoirs for urinary diversion who were examined with the same technique 3 years earlier, and relate the changes to kidney function and variables reflecting bone metabolism. A total of 28 patients with Kock ileal reservoirs to the skin (23) or urethra (5) were reinvestigated 3 years after the first measurement. BMD was measured in the lumbar spine, femur and whole body with DXA. Bone specific alkaline phosphatase, osteocalcin, parathyroid hormone (PTH), calcitonin and chloride were also determined in serum. GFR was determined from the plasma clearance of 51Cr-EDTA. The mean values for BMD expressed in percentage of corresponding mean values for age-matched controls (BMD%) were almost identical after 3 years. Only osteocalcin levels correlated with the BMD% values. However, significant positive correlations were found between GFR and the observed individual changes in BMD% over the 3 years in spite of the fact that most GFR values were fairly normal. Enhanced bone loss was associated with high concentrations of osteocalcin and bone specific alkaline phosphatase. Comparisons with blood gas analyses and determination of 1,25 dihydroxyvitamin D performed in the previous study indicate to us that the relation between reduced GFR and low mineral content might, in part, be related to a low-grade metabolic acidosis and reduced availability of the biologically active vitamin D hormone. The conclusion to be drawn is that urinary diversion with a Kock reservoir does not regularly cause bone demineralization. However, patients with even moderately reduced GFR appear to be at risk for developing osteoporosis in the long-time run.
Adult↗
Expression of cholecystokinin-B/gastrin receptors in medullary thyroid cancer.
OBJECTIVE: To characterise the cholecystokinin (CCK) receptor subtypes in medullary thyroid cancer by measuring the expression of CCK-A and CCK-B/gastrin receptor mRNA. DESIGN: Open study. SETTING: Teaching hospital, Sweden. SUBJECTS: 6 patients with medullary thyroid cancer. INTERVENTION: Pentagastrin stimulation test and measurement of calcitonin concentration. Biopsy specimens were analysed using reverse transcription polymerase chain reaction (RT-PCR). MAIN OUTCOME MEASURE: Presence of CCK-A and CCK-B/gastrin receptors. RESULTS: All 6 patients with medullary thyroid cancer had positive pentagastrin tests preoperatively. CCK-B/gastrin receptors but not CCK-A receptors were detected by RT-PCR in all six biopsy specimens. By contrast, no CCK receptors were found in normal thyroid tissues or in other thyroid tumours (follicular adenoma, papillary carcinoma, or anaplastic carcinoma). CONCLUSION: The presence of CCK-B/gastrin receptors in medullary thyroid tumours may have important clinical implications.
Adult↗
The red cell mass, plasma erythropoietin and spleen size in apparent polycythaemia.
It has been shown previously that measurement of the spleen size and plasma erythropoietin (EPO) concentration are valuable adjuncts in the diagnostic work-up of patients with polycythaemia vera. The aim of the present work was to evaluate their value in the assessment of apparent polycythaemia (AP). Therefore, over a 24-month period we routinely performed bone marrow biopsies, measurement of red cell mass (RCM) and plasma volume (PV), spleen size determination by gamma camera scintigraphy and determination of the plasma EPO concentration in consecutive patients referred to us because of elevated values for packed cell volume (>0.48 in females and >0.51 in males). After having excluded patients with clonal and secondary polycythaemias we were left with 38 patients (27 males and 11 females) with AP. In all of them the measured RCM was within normal range, i.e. <36 ml/kg for males and <32 ml/kg for females. The subjects were characterized by moderate increase in RCM and a concomitant moderate decrease in PV. Thus, as an average the measured RCM exceeded the predicted values by 14% in males and by 12% in females; conversely, as compared to the predicted values the average measured value for PV was reduced by 17% in males and by 8% in females. The average RCM for males was 29+/-3 ml/kg; the corresponding figure for females was 23+/-4 ml/kg. It was shown that 86% of the subjects had plasma EPO concentrations within the control range; the remaining had values slightly above or below the control range. The mean posterior spleen scan area was 57+/-16 cm2 and mean left lateral area 57+/-17 cm2; the reference value for spleen scan area (for both projections) is 57+/-12 cm2. Of the patients 35/38 (92%) had a spleen scan area within the mean+2SD for controls and 38 subjects (100%) had values within the mean+3SD. It is concluded that measurement of plasma EPO and a careful assessment of the spleen size should always be considered in the evaluation of patients with elevated values for venous packed cell volume.
Adult↗
Factors influencing vaginal fetal fibronectin concentrations during pregnancy.
In order to evaluate factors influencing fetal fibronectin concentrations during pregnancy a total of 312 vaginal samples for fetal fibronectin measurements and microbiological culture were collected and later included in a stepwise regression analysis. Preterm premature rupture of membranes, a modified Bishop score >/=6 (p < 0.0001), a low vaginal polymorphonuclear leukocyte count (p < 0. 002), the presence of Enterococcus faecalis (p < 0.0001), Prevotella species (p < 0.05), a bacterial vaginosis-associated flora (p < 0. 05), and a non-lactobacilli-dominated vaginal flora (p < 0.05) were associated with an elevated vaginal fetal fibronectin concentration.
Adult↗
[Study and treatment of heart failure require new approaches. Natriuretic peptides can be safe and simple diagnostic and outcome measures].
Analysis of plasma natriuretic peptides and related propeptide fragments may be a cost-effective aid to diagnostic evaluation and treatment follow-up in cases of heart failure. In diagnostic potential such variables may constitute first-line measures of high negative predictive value, allowing further examination, e.g. by echocardiography, in cases where values are above the respective cut-off levels. However, in many cases evaluation of published reports is rendered difficult by their omission of information on such pre-analytical variables as blood sampling and storage, and drug therapy. Moreover, different analytical methods may yield widely divergent results. Thus, before such assays are introduced in general use, their long-term validity needs to be ensured, for instance by consistency in calibration, and measurements need to be made in representative series of unselected patients for the determination of appropriate cut-off levels.
Amino Acid Sequence↗
[Pheochromocytoma. Methoxycatecholamines in nocturnal urine and chromogranin in EDTA-blood should be measured first].
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Catecholamines↗
[Hypothyroidism--a common disease with many faces. Thyroid function in women should be regularly examined].
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Female↗
Effect of a mild infection on serum ferritin concentration--clinical and epidemiological implications.
OBJECTIVES: To study the distribution of serum ferritin concentration in adolescent boys and girls with and without a preceding mild infection. DESIGN: The prevalence of iron deficiency was studied in two representative samples. The first sample from 1990 comprised 207 boys and 220 girls. The second sample from 1994 included 620 boys and 624 girls. In total 1675 adolescents, 15-16 y old, 827 boys and 844 girls were studied. RESULTS: A significant shift of serum ferritin concentration towards higher values was observed in those who reported an upper respiratory infection with fever during the preceding month (P<0.001). Significant differences were found between serum ferritin values in healthy, not infected adolescents and serum ferritin values in those with ongoing infection, both in boys and girls in the two materials (P < 0.01), and in those with a mild infection during the preceding three weeks. CONCLUSIONS: The prevalence of recent infection should be included as information when trying to assess the prevalence of iron deficiency on the basis of serum ferritin measurements and when examining relationships between iron status and composition of the diet. The findings imply that differences in prevalence of iron deficiency between different studies might partly be explained by differences in prevalence of simple respiratory infections. The diagnostic sensitivity of the serum ferritin assay for iron deficiency, using conventional reference limits, decreases for subjects with recent such infections; similarly, there will be a decrease in the diagnostic specificity for haemochromatosis.
Adolescent↗
The relations of microalbuminuria to ambulatory blood pressure and myocardial wall thickness in a population.
OBJECTIVES: To examine the relationship between microalbuminuria (20-200 microg min(-1)) and 24 h ambulatory blood pressure and heart wall thickness, in a representative population sample of men and women aged 56-65 years. DESIGN: Every second individual aged 56-65 years (n=488) in the district, was invited for a health examination, which included determination of urinary albumin and creatinine (overnight sample). The highest and lowest decentile of urinary albumin/creatinine ratio were compared. SETTING: The district of the Primary Health Care and Research Centre of Mölnlycke, Sweden. SUBJECTS: After excluding 2 individuals with a urinary albumin excretion exceeding 200 microg min(-1). 26 subjects (group 1) could be compared with 27 subjects in the lowest decentile (group 2). MAIN OUTCOME MEASURES: Comparison between the determinations of the ambulatory blood pressure and echocardiographic variables in the two groups. RESULTS: Group 1 had significantly higher 24 h ambulatory blood pressure, and heart septum and posterior wall thickness as well as significantly higher fasting blood glucose and serum triglyceride concentrations. The differences in blood pressure (P < 0.05) but not heart wall thickness remained significant (P<0.05) after excluding subjects with hypertension, angina pectoris, treated diabetes mellitus, and/or history of heart or cerebrovascular disease. When excluding individuals with both treated and untreated diabetes mellitus, fasting blood glucose concentration was higher in group 1. The waist-hip ratio, weight and body mass index did not differ between the groups. CONCLUSIONS: The findings indicate that microalbuminuria is related to signs of cardiovascular and metabolic influence and therefore could be a valuable tool for grading the risk of later cardiovascular morbidity.
Aged↗
Advantages of serum pepsinogen A combined with gastrin or pepsinogen C as first-line analytes in the evaluation of suspected cobalamin deficiency: a study in patients previously not subjected to gastrointestinal surgery.
OBJECTIVES: Since there is a significant overlap in serum cobalamin concentrations between healthy and cobalamin-deficient individuals, we wanted to compare two different principles for use as supplementary tests to serum cobalamin concentration in patients with suspected cobalamin malabsorption and deficiency. DESIGN: Clinical study of consecutive patients. SETTING: The catchment area of Sahlgrenska University Hospital, Göteborg. SUBJECTS: A total of 112 patients with suspected cobalamin deficiency who had not previously undergone gastrointestinal surgery. INTERVENTIONS: Gastroduodenoscopy with biopsies taken from the gastric body and the duodenum, Schilling test, and measurement of serum methylmalonic acid (MMA), total homocysteine (Hcy), pepsinogens A and C, and gastrin. MAIN OUTCOME MEASURES: Number of patients with gastric body atrophy identified with the combination of MMA and Hcy, and pepsinogen A combined with pepsinogen C or gastrin. RESULTS: About 95% of the patients with severe gastric body atrophy had abnormal concentrations of serum pepsinogen A and/or gastrin or pepsinogen A/C ratio, whereas 65% had abnormal metabolite concentrations. Serum pepsinogen A combined with pepsinogen C identified 100%, and combined with gastrin 88%, of the patients with gastric body atrophy and elevated metabolite tests, and 67 and 75%, respectively, of those who had not yet developed elevated metabolite tests. CONCLUSIONS: Pepsinogen A, combined with pepsinogen C or gastrin, should be the first option in evaluating patients with suspected cobalamin deficiency who have not previously undergone gastrointestinal surgery.
Adult↗
Are current methods of measurement of erythropoietin (EPO) in human plasma or serum adequate for the diagnosis of polycythaemia vera and the assessment of EPO deficiency?
Current methodology for the immunoassay of erythropoietin (EPO) in human plasma or serum is reviewed, with an emphasis on measurement of EPO concentrations in the low and normal ranges, analytical interference and blood sampling requirements. In only 2 out of 8 research or in-house immunoassays reported since 1987 was there evidence that patients with polycythaemia vera (PV) could be identified, PV being an EPO-independent form of polycythaemia in which EPO concentrations are low in untreated cases. The same was true for only 1 out of 13 currently available kit methods. Remarkable differences in sample stability have been observed with different methods. Measurement of EPO in serum is recommended in most published articles. However, only EDTA plasma seems to be acceptable for the one generally available method with proven high diagnostic sensitivity for PV. It is concluded that most EPO assay methods have not been shown to be adequate for the measurement of the low EPO concentrations, and thus have poor diagnostic sensitivity for PV. It is inferred that they might not be appropriate to assess states of EPO deficiency. Only when a sufficiently sensitive diagnostic method becomes generally available will it be possible to define the various causes of low EPO concentrations. As in other fields of polypeptide hormone measurement, further developments in the field of EPO assay may be expected to be important in diagnostic medicine.
Drug Stability↗
Serum antibodies to H+,K+-ATPase, serum pepsinogen A and Helicobacter pylori in relation to gastric mucosa morphology in patients with low or low-normal concentrations of serum cobalamins.
OBJECTIVES: To compare the diagnostic performance of serum antibodies to H+,K+-ATPase (EC 3.6.1.36), serum pepsinogen A (EC 3.4.23.1) and the Schilling test in diagnosing chronic atrophic body gastritis; to study the interrelationships between H+,K+-ATPase antibodies, serology for Helicobacter pylori, and gastric morphology. DESIGN: Patients with suspected cobalamin deficiency and serum cobalamin < 200 micromol/l were investigated using upper gastrointestinal endoscopy, the Schilling test and serum tests for H+,K+-ATPase antibodies, pepsinogen A, and H. pylori. SETTING: The Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. PATIENTS: Ninety seven consecutively referred patients. MAIN OUTCOME MEASURES: Sensitivity and specificity of assays for serum H+,K+-ATPase antibodies, serum pepsinogen A, and the Schilling test. RESULTS: Assays of serum antibodies to H+,K+-ATPase and of serum pepsinogen A displayed equal diagnostic sensitivity for atrophic gastritis (around 0.90 for the severe forms) and higher than that for the Schilling test (0.65). The diagnostic specificity for pepsinogen A (1.0) was higher than for H+,K+-ATPase antibodies (about 0.80). The prevalence of antral gastritis and positivity for H. pylori antibodies declined with the transition of body gastritis into severe atrophy, while the prevalence of H+,K+-ATPase antibodies increased. CONCLUSION: Pepsinogen A is preferable to serum H+,K+-ATPase antibodies in the diagnosis of gastric body mucosal atrophy. The formation of H+,K+-ATPase antibodies does not seem to be a primary event in the development of gastric body muscosal atrophy.
Adult↗
Plasma erythropoietin by high-detectability immunoradiometric assay in untreated and treated patients with polycythaemia vera and essential thrombocythaemia.
By using an immunoradiometric method with a stated detection limit of < or =1 IU/l (stated normal reference limit in adults 3.7-16 IU/l) we determined EDTA-plasma erythropoietin (EPO) in 58 patients with polycythaemia vera (PV) and 49 patients with essential thrombocythaemia (ET). At the time of blood sampling, 20 of the PV patients were newly diagnosed and untreated, 23 were treated by phlebotomy only, and 30 also received myelosuppressive treatment (with 32P, hydroxyurea or alpha-interferon). Of the ET patients 24 were untreated and 28 received myelosuppressive therapy. For comparison plasma EPO was also determined in 10 patients with pseudopolycythaemia (PP). In this latter group the results for plasma EPO agreed well with the cited normal reference limits. The majority of untreated PV patients (12/20) had undetectable plasma EPO concentration, and the remainder all had values below the lower normal reference limit. Plasma EPO in PV was not significantly influenced by phlebotomy therapy. Twelve of the 24 untreated ET patients (50%) had plasma EPO values below the reference interval (undetectable in 2 patients). The mean EPO concentration was significantly lower in PV patients receiving phlebotomy therapy than in patients with untreated ET. In the total material of PV and ET treated with myelosuppressive agents the PV patients showed significantly lower values for EPO concentration than did patients with ET. The present results support the view that EPO measurements by high-detectability methods are diagnostically useful and should be included in the panel of new criteria for the diagnosis of PV.
Adult↗
Follitropin (FSH) deficiency in an infertile male due to FSHbeta gene mutation. A syndrome of normal puberty and virilization but underdeveloped testicles with azoospermia, low FSH but high lutropin and normal serum testosterone concentrations.
We studied a man who sought medical attention at age 28 years because of infertility in both his first and second marriages. His sexual development appeared to have been normal, with normal puberty and virilization, and normal libido and sexual potency. At examination, his testicles were small and soft; otherwise he had a normal physical appearance. Evaluations revealed azoospermia, undetectable in serum before and after 100 microg of intravenously administered gonadotrophin releasing hormone, but moderately elevated lutropin concentration with a brisk rise after gonadotrophin releasing hormone. The alpha subunit concentration was normal before and after gonadotrophin releasing hormone; that of inhibin B was very low. Analysis of the follitropin beta gene, exon 3, revealed a Cys82 --> Arg mutation (TGT --> CGT). Judging from studies of the biosynthesis of the chorionic gonadotrophin beta subunit one may conclude that inability to form the first intramolecular disulphide bond in the follitropin beta subunit results in an abnormal tertiary structure during follitropin beta biosynthesis with extensive intracellular degradation of the products, inability to associate with the alpha subunit and defective glycosylation, as well as inability to form a biologically active hormone. This first male case of follitropin deficiency thus defines a new syndrome of male infertility.
Adult↗
Improved nasal breathing in snorers increases nocturnal growth hormone secretion and serum concentrations of insulin-like growth factor 1 subsequently.
In snoring men improved nasal breathing during sleep has been shown to decrease snoring and morning tiredness. The aim was to evaluate whether improved nasal breathing had any effect on growth hormone (GH) secretion, the nocturnal secretion of GH being associated with deep sleep. Forty-two snoring men, mean age 45 years and mean body mass index 26 kg.m-2, slept every night during one month with the Nozovent nostril dilator. Before and at the end of the test period, we analysed serum insulin-like growth factor 1 (IGF-1), thyrotropin (TSH), free thyroxine (free T4), free 3,5,3'-triiodothyronine (free T3), cortisol and testosterone in blood sampled at 08:00 h. Fifteen of the 37 snoring men who completed the study experienced a reduction in snoring and were less tired in the morning during the test period. In this group, the mean IGF-1 concentration was significantly increased (p < 0.05) after one month. There was no significant difference in mean IGF-1 level between the snorers and a population sample. Likewise, TSH, free T4, free T3, cortisol and testosterone concentrations were within normal limits. Snorers with reduced snoring and morning tiredness due to improved nasal breathing showed an increase in morning IGF-1 concentration which can probably be explained by higher nocturnal GH secretion induced by more deep sleep.
Adult↗
A natural transactivation mutation in the thyroid hormone beta receptor: impaired interaction with putative transcriptional mediators.
The syndrome of resistance to thyroid hormone is characterized by elevated serum free thyroid hormones, failure to suppress pituitary thyrotropin secretion, and variable peripheral refractoriness to hormone action. Here we describe a novel leucine to valine mutation in codon 454 (L454V) of the thyroid hormone beta receptor (TR beta) in this disorder, resulting in a mutant receptor with unusual functional properties. Although the mutant protein binds ligand comparably to wild-type receptor and forms homo- and heterodimers on direct repeat, everted repeat, or palindromic thyroid response elements, its ability to activate transcription via these elements is markedly impaired. The hydrophobic leucine residue lies within an amphipathic alpha-helix at the carboxyl terminus of TR beta and the position of the homologous residue in the crystal structure of TR alpha indicates that its side chain is solvent-exposed and might interact with other proteins. We find that two putative transcriptional mediators (RIP140 and SRC-1) exhibit hormone-dependent association with wild-type TR. In comparison, the interaction of this natural mutant (L454V) and artificial mutants (L454A, E457A) with RIP140 and SRC-1 is markedly reduced. Furthermore, coexpression of SRC-1 is able to restore the transcriptional activity of the L454V mutant receptor, indicating that the interaction of this residue with accessory proteins is critical for transcriptional activation. Finally, the occurrence of the L454V mutation in resistance to thyroid hormone, together with impaired negative regulation of the thyroid-stimulating hormone alpha promoter by this mutant, suggests that the amphipathic alpha-helix also mediates hormone-dependent transcriptional inhibition, perhaps via interaction with these or other accessory factors.
Adaptor Proteins, Signal Transducing↗