The yield of a diagnostic hospital dyspnoea clinic for the primary health care section.

OBJECTIVE: To investigate the impact of a combined examination programme with treatment advice on patients from general practice with dyspnoea. DESIGN: Prospective study with 6 months followup. SETTING: Regional hospital offering care for patients from 74 general practitioners. SUBJECTS: A total of 284 consecutive patients referred from general practice with dyspnoea. INTERVENTIONS: Patients were subjected to a combined examination programme including physical examination, ECG, chest X-ray, lung spirometry, echocardiography and routine laboratory tests. MAIN OUTCOME MEASURES: (i) Relationship between a diagnosis made by the referring general practitioner and the diagnosis based on the combined examination programme. (ii) The impact of the investigation programme and resulting therapeutic advice on dyspnoea after 6 months. RESULTS: Only in 39% of the patients there was concordance of the diagnoses on referral and the diagnosis based on the examination programme. Heart failure and lung disease was suspected in 126 and 79 patients, respectively, but these diagnoses were confirmed in only one-third to half of the patients. Conversely heart failure was revealed in 13 of 107 patients not suspected of heart failure (12%) and lung disease in 45 of 154 patients not suspected of pulmonary disease (29%). A change of treatment was suggested in 64% of all patients. After 6 months, improvement of dyspnoea was seen in more than half of the patients. In patients in whom the changes of medical treatment were completed, 61% expressed improvement in dyspnoea, whereas improvement of dyspnoea was recorded in only 34% of patients in whom the recommended treatment advice was not taken (P < 0.01). CONCLUSION: (i) In most patients it seems to be too difficult to establish the background of dyspnoea in general practice. (ii) There appears to be a substantial chance of improvement in patients with dyspnoea, in particular for patients who act on treatment advice based on an integrated examination programme; the chance of improvement is almost twice as good as in patients who are not capable to do so.

An enzyme-linked immunosorbent assay for plasma-lactoferrin. Concentrations in 362 healthy, adult blood donors.

Very different concentrations of plasma-lactoferrin in healthy adults have been reported in the literature. We compared three commercially available lactoferrins and lactoferrin purified in our laboratory as calibrators in an ELISA. No statistical differences among these preparations of lactoferrin were detected. The concentration of purified lactoferrin was measured by dry weight, and efforts were made in order to minimize loss of purified lactoferrin by adhesion to tubes etc. and thus, secure accuracy of the method. Dilutions were made in PBS 0.01 mol l-1 with NaCl 0.436 mol l-1, (NH4)2SO4 0.5 mol l-1, BSA 5 gl-1 and normal rabbit IgG 10 mg l-1, which was shown to give parallel dilution curves of primary calibrator, secondary calibrator and plasma samples. No significant difference in the content of lactoferrin in neutrophils (median; range) among men (1.78; 0.83-4.48 micrograms 10(-6) neutrophils; n = 20) and women (2.12; 1.16-9.30 micrograms 10(-6) neutrophils; n = 14) was found. Lactoferrin was analysed in EDTA-plasma obtained from 135 female and 227 male blood donors. Median concentrations were 84.7 and 97.8 micrograms l-1 respectively, while 2.5% and 97.5% reference limits (with 90% confidence intervals) were estimated to 42.9 (38.7-47.4) micrograms l-1 and 166.9 (151.0-186.3) micrograms l-1 for women and 52.3 (49.1-55.6) micrograms l-1 and 189.9 (175.9-206.4) micrograms l-1 for men, respectively.

Identification of patients with hereditary haemochromatosis by magnetic resonance imaging and spectroscopic relaxation time measurements.

A total of 4302 healthy blood donors were screened for elevated serum ferritin and transferrin saturation. Fifteen had increased serum ferritin at a follow-up examination. Five relatives of these donors also entered the study. Eleven patients had elevated liver iron concentrations, while five had normal liver iron concentrations. The R2 relaxation rate in the liver was first measured with a conventional multi-spin-echo imaging sequence, and then by a volume-selective spectroscopic multi-spin-echo sequence, in order to achieve a minimum echo time of 4 msec. No correlation was found between the relaxation rate R2 and the liver iron concentration, when R2 was calculated from the imaging data. Multi-exponential transverse relaxation could be resolved when the spectroscopic sequence was used. A strong correlation between the initial slope of the relaxation curve and the liver iron concentration was found (r = 0.90, p < 0.001). Signal intensity ratios between liver and muscle were calculated from the first three echoes in the multi-echo imaging sequence, and from a gradient echo sequence. A strong correlation between the logarithm of the signal intensity ratios and the liver iron concentration was found. Although both spectroscopic T2 relaxation time measurements and signal intensity ratios could be used to quantify liver iron concentration, the gradient echo imaging seemed to be the best choice. Gradient echo imaging could be performed during a single breath hold, so motion artifacts could be avoided. The accuracy of liver iron concentration estimates from signal intensity ratios in the gradient echo images was about 35%.

Screening for haemochromatosis: prevalence among Danish blood donors.

Hereditary haemochromatosis is an autosomal recessive disease that is genetically expressed by excessive accumulation of iron in the tissues, resulting in cirrhosis, diabetes mellitus, cardiomyopathy and hypogonadism. As the disease may be diagnosed before the appearance of symptoms, and prevented by repeated phlebotomies, there are strong implications for adoption of a screening procedure. Determinations of transferrin saturation (TS) and serum ferritin concentration (SF) were used to screen 4302 blood donors, who were selected for follow-up studies if they fulfilled any of the following three criteria: (i) TS greater than or equal to 0.7; (ii) TS greater than or equal to 0.5 together with SF greater than or equal to 150 micrograms l-1; (iii) SF greater than or equal to 300 micrograms l-1. A total of 58 subjects who fulfilled at least one of these criteria were reinvestigated, after which 18 individuals still fulfilled at least one criterion. Fifteen subjects having SF greater than or equal to 300 micrograms l-1 were offered liver biopsy and thirteen of these accepted. In one individual, no stainable iron was detected, and two subjects did not fulfil the previously established diagnostic criteria for the diagnosis of hereditary haemochromatosis. Ten subjects who had a high TS and liver iron grade 2-4 according to Bassett were classified accordingly as homozygotes. On the basis of these results, the prevalence of haemochromatosis in Denmark was estimated to be 0.0037-0.0046.

Variations in serum erythropoietin and transferrin receptor during phlebotomy therapy of hereditary hemochromatosis: a case report.

Serum levels of transferrin receptor and erythropoietin were determined in 2 patients with hereditary hemochromatosis undergoing phlebotomy therapy. The objective of the study was to determine changes in serum transferrin receptor and serum erythropoietin occurring during therapy, and to investigate if such changes could be useful to monitor the therapy. The study showed that serum transferrin receptor, and to a lesser extent serum erythropoietin, may be better parameters than serum ferritin as indicators of when phlebotomy should be discontinued. The most sensitive parameter, however, appeared to be the serum transferrin receptor/ferritin ratio.

Elimination of PBBs in rats. Effect of mineral oil and/or feed restriction.

Rats were fed polybrominated biphenyls (PBBs) at 0.1 to 100.0 ppm for 14 d and then treated to hasten the removal of PBBs with 0, 5, or 10% mineral oil (MO) and/or 0, 15, 30, or 45% feed restriction (FR) for 21 d. PBB body burdens were determined at d 14 and expressed on a log-log basis by Y = 0.91X + 2.179 (r2 = 0.974), where X = log of PBB concentration in diet (ppm) and Y = log of PBB body burden (micrograms). After 21 d withdrawal, body burdens were expressed by the equation Y = 0.787X + 2.218 (r2 = 0.95). The most effective withdrawal treatment was 10% MO + 45% FR producing a reduction of body burdens inversely related to prior body burdens (69% at 0.1 ppm to 23% at 100 ppm). Body weights and fat content were significantly (p less than or equal to .05) reduced by feed restriction, with fat content only 39% of controls at 21 d off. Mortality averaged 0, 13.6, and 35.8% for rats fed 0, 5, or 10% MO, and 25, 15, 8.6, and 3.7% for rats feed restricted at 0, 15, 30, and 45%, respectively. Histopathology of the dead and moribund rats indicated that the clinical signs were not characteristic of PBB toxicity. In a second experiment, safflower oil at 3.5% or excess vitamins prevented the mortality and clinical signs associated with MO during withdrawal from 100 ppm PBBs. Based on these data and those in the literature, PBBs interfere with vitamin utilization.

Screening for haemochromatosis: influence of analytical imprecision, diagnostic limit and prevalence on test validity.

Serum ferritin (S-ferritin) and the saturation of transferrin iron-binding capacity (TIBC-sat) were evaluated as screening procedures for idiopathic haemochromatosis in a non-diseased population. Special attention was paid to the influence of the analytical quality, but the effects of prevalence and discrimination limits were also considered. Changes in the analytical quality for S-ferritin and TIBC-sat used as single tests highly influenced the number of false test-positives. Increasing the coefficient of variation from 0.0 to 0.2 resulted in nearly a doubling of the number of false test-positives to be further investigated. Using even a high, yet achievable analytic quality with a low coefficient of variation of 0.056 and 0.059 for S-ferritin and TIBC-sat respectively, screening procedures had unacceptably high fractions of false test-positives and false test-negatives associated with any discrimination limit. If the prevalence of haemochromatosis is 0.003, the predictive value of a positive test result did not exceed 0.05, accepting a fraction of false test-negatives of 0.025. This was found to be too low for a screening test to be used in the general population. The combined use of S-ferritin and TIBC-sat resulted in higher performance with a sensitivity of 0.90, a specificity of 0.99 and a predictive value of a positive test result of 0.29 if a fraction of misclassification of 0.01 is accepted for each.

[Hemoglobin concentration and iron stores in female blood donors]. / Haemoglobinkoncentration og jerndepoter hos kvindelige bloddonorer.

The blood hemoglobin concentration (B-Hb) and iron indices were measured in 1,856 consecutive female blood donors. The blood hemoglobin distribution was Gaussian except for an excess of high values. According to criteria defined by the WHO, 9.5% of the population were anemic, but using several criteria only 0.9% had iron deficiency anemia in agreement with the blood hemoglobin distribution curve. The distribution of the S-ferritin values was log Gaussian. Nearly 1/5 of female blood donors had low iron stores despite widespread use of iron supplements. The weak correlation detected between the B-Hb values and the S-ferritin level points to an increased risk of anemia in female blood donors. Regular determination of the S-ferritin level in female blood donors or extended use of iron supplements may contribute to the establishment of adequate iron stores and hence the prevention of anemia.

[Iron stores, iron deficiency and iron supplementation]. / Jerndepoter, jernmangel og jernberigelse.

In order to assess the prevalence of iron deficiency in the Danish population, a randomised cross sectional investigation was carried out one year after repealing of the order from 1939 concerning supplementing of corn products with iron. A randomised group of 198 persons divided into ten groups of 20 persons with equal numbers of men and women in the age group 20-69 years was submitted to determinations of serum-iron, serum-transferrin and serum-ferritin. The prevalence of iron deficiency as determined by serum-ferritin values of below 15 micrograms/l was 18% and 12% respectively, for women under and over 45 years while iron deficiency determined by transferrin saturation under 16% was 18% for both groups. 6% of the women under 45 years had severe iron deficiency as determined by low transferrin saturation and low ferritin. The prevalence among men was 1% and 3% as assessed by serum-ferritin levels and transferritin saturation. These results were compared with corresponding population investigations from Sweden where iron enrichment is the highest in the world and the sale of iron tablets is the greatest in the world. No significant differences in the frequency of latent iron deficiency could be demonstrated but the number of persons with severe iron depletion appears to be less in Sweden. Differences in the methodological procedures, however, cannot be excluded.

Iron storage disease in parents and sibs of infants with neonatal hemochromatosis: 30-year follow-up.

Neonatal hemochromatosis (NH), an uncommon and generally fatal disorder of infancy, is defined by hepatic disease of antenatal onset, generally manifest at birth, and by stainable iron in a tissue distribution like that seen in heritable adult-onset hemochromatosis (HH). It is not known if parents and sibs of infants with NH are at risk of iron storage disease in later life. We provide 30-year follow-up for iron overload of a family in which 6 of 9 children died in utero or early in the neonatal period. Four of the 6 came to autopsy, where severe liver disease was found; in 3 of the 4, autopsy material could be reviewed. These 3 children had NH. Studies 30 years later did not identify HH or other iron storage disease in the parents or surviving sibs. These findings suggest that first-degree relatives of persons with NH are not necessarily at increased risk of iron storage disease in later life.

Screening with zinc protoporphyrin for iron deficiency in non-anemic female blood donors.

Iron-depleted donors are at increased risk of developing anemia; if these donors could be identified by a screening test, iron supplementation or decreased donation frequency could be considered. Tests to determine serum ferritin, blood hemoglobin, and erythrocyte (Erc)-zinc protoporphyrin concentrations were examined in 679 consecutive female blood donors to identify donors with non-anemic iron deficiency. The test to determine serum ferritin is expensive and slow, whereas the two latter tests are rapid and less costly and could therefore be used for screening. Women in the fertile age groups had the lowest average serum ferritin values. In all, 93 women (13.7%) had depleted iron stores, as indicated by serum ferritin concentrations less than 14 micrograms/L. In these women, a much better correlation was found between Erc-zinc protoporphyrin and serum ferritin (rs = -0.49, P less than 0.001) than between blood hemoglobin and serum ferritin (rs = 0.31, P less than 0.01). These findings suggest that measurement of Erc-zinc protoporphyrin is superior to that of blood hemoglobin in identifying donors with non-anemic iron deficiency.

[Blood sedimentation rate in healthy persons]. / Saenkningsreaktionen hos klinisk raske.

The erythrocyte sedimentation rate was determined using the Westergren method in 4,202 consecutive blood donors aged 18-65 years. The distribution of the values was log normal for both females and males. The median value was highest in females for all age classes and although both the median and the range rose in both sexes with increasing age, the increase was most pronounced in females. Used as a screening test, the fraction of false positives showed a marked rise after age 45 years using cut-off values of 15 and 20 mm/hr, while the increase took place after age 55 years when 25 mm/hr was applied. The results point to increasing the most frequently used cut-off values and one cut-off value for premenopausal women and another, higher, value for postmenopausal women may be considered. For men a single cut-off value seems adequate.

Metastatic tumour of the epididymis. A case report.

A case of adenocarcinoma of the stomach was initially diagnosed by detection of epididymal metastases. The case is presented and the importance of histologic examination of peroperatively removed tissue is emphasized.

Myoglobin, creatine kinase and creatine kinase subunit-beta in serum from patients and relatives with hypokaliaemic familial periodic paralysis.

Increased levels of serum myoglobin (S-myoglobin) were found in 6 investigated patients with hypokaliaemic familial periodic paralysis (hypoKPP) in their habitual condition. Furthermore, in 3 of the 6, increased levels of serum creatine kinase (S-CK) were found. These findings support the hypothesis that hypoKPP is a permanent myopathy, which is aggravated during attacks. It was found that 1 definite carrier had elevated S-myoglobin and among healthy relatives 6/11 had elevated S-myoglobin and 3/11 elevated S-CK. The use of S-myoglobin and S-CK for carrier detection is discussed.