Interleukin-10 gene promoter region polymorphisms are not associated with BCG osteitis in vaccinated infants.

SETTING: Complications arising from bacille Calmette-Guérin (BCG) vaccination were recorded in a national register in Finland until 1988. In the period 1960-1988, 222 patients suffered from BCG osteitis. OBJECTIVE: To evaluate whether single nucleotide polymorphisms (SNPs) in the promoter region of the gene encoding interleukin 10 (IL-10) are associated with BCG osteitis after vaccination in neonates. DESIGN: Blood samples of 132 former BCG osteitis patients now aged 21-49 years were analysed in a controlled study for IL10 rs1800896 (-1082G/A), rs1800871 (-819C/T), rs1800872 (-592C/A) and rs1800890 (-3575T/A) polymorphisms. RESULTS: The frequencies of genotypes of IL10 rs1800896, rs1800871, rs1800872 and rs1800890, the frequencies of variant genotypes and the frequencies of major or minor alleles did not differ between patients and controls. Furthermore, the frequencies of the eight possible combinations of the three IL10 alleles located close to each other (IL10 rs1800896, IL10 rs1800871 and IL10 rs1800872) were surprisingly similar. CONCLUSION: Our results suggest that polymorphisms of the IL-10 encoding gene do not play a central role in the development of complications due to BCG vaccination, although the IL10 gene, especially IL10 rs1800896 (-1082G/A) polymorphism, is known to be associated with tuberculosis risk in Europeans and North Americans.

Ultrasonography of the thyroid gland in pregnancies complicated by autoimmune thyroid disease.

Thyroid function and ultrasonographically determined thyroid volume were studied in nine pregnant women with diagnosed autoimmune thyroid disease at regular intervals during pregnancy and two months after delivery. The results were compared to the findings in ten healthy pregnant women. In ultrasound examinations seven of the patients showed definite morphological changes such as hypoechogeneity and inhomogeneity of the thyroid gland, which did not change during the course of pregnancy nor during the post-partum period of eight weeks. There were no morphological changes in the thyroid glands of the control group. The mean thyroid volume did not significantly change during pregnancy and after delivery in both the patient group and controls. The mean thyroid volume was smaller in the study group, with 7.55 ml (SD 6.01) compared to the controls with 11.29 ml (SD 5.61), a difference which was not statistically significant. Neither course of pregnancy nor fetal outcome was influenced by inactive autoimmune disease of the thyroid.

Absorption of bile acids after ileoanal anastomosis.

Absorption of bile acids was investigated using 75Se-homotaurocholate (SeHCAT) in 27 patients with ileoanal anastomosis and J-pouch, 7 patients with conventional ileostomy and 9 non-operated patients with ulcerative colitis. Retention of SeHCAT at seven days was higher in non-operated patients than in patients with ileoanal anastomosis (P less than 0.001) or conventional ileostomy (P less 0.01). There was no difference in retention of SeHCAT between patients with ileoanal anastomosis or conventional ileostomy. Malabsorption of bile acids was not associated with changes in blood chemistry or faecal fat excretion. Patients with ileoanal anastomosis and low retention of SeHCAT had more severe villous atrophy of the pouch mucosa than those with high retention (P less than 0.05). In conclusion, both patients with ileoanal anastomosis and conventional ileostomy have impaired absorption of bile acids when compared with non-operated patients with ulcerative colitis. In patients with ileoanal anastomosis, impairment of bile acid absorption is related to villous atrophy of the pouch mucosa.

Adrenal pheochromocytoma-ganglioneuroma producing catecholamines and various neuropeptides.

A 65-year-old woman presenting with back pain, difficulties in walking and watery diarrhea. A right adrenal tumor and high excretion of catecholamines were found. Laboratory examinations showed raised levels of vasoactive intestinal polypeptide, pancreatic polypeptide, gastrin and calcitonin. Histology showed a combined pheochromocytoma-ganglioneuroma. The neoplastic cell population was immunohistochemically shown to contain tyrosine hydroxylase, neuropeptide Y, met-enkephalin, substance P, vasoactive intestinal polypeptide, calcitonin and calcitonin gene-related peptide. Postoperatively, the patient recovered fully and the hormone levels returned to normal.

Intravenous streptokinase treatment and serum C-reactive protein in patients with acute myocardial infarction.

Serum concentrations of C-reactive protein were studied in 23 patients with acute myocardial infarction. In 14 patients who did not receive thrombolytic treatment there was a linear relation between infarct size (determined by serial creatine kinase-MB determinations and thallium-201 isotope emission tomography) and the C-reactive protein response. The correlation coefficient between the concentration-time integrals of creatine kinase-MB and C-reactive protein was 0.96. The correlation coefficient between the creatine kinase-MB concentration-time integral and the peak serum value of C-reactive protein was 0.93. In the nine patients who received intravenous streptokinase treatment there was also a positive correlation between the concentration-time integrals of creatine kinase-MB and C-reactive protein. The relation, however, depended on the success of the treatment. In patients with successful reperfusion the C-reactive protein response was only approximately 20% of that in patients in whom reperfusion failed or who received no thrombolytic treatment and who were matched by infarct size. When thrombolysis was successful the correlation coefficient between the concentration-time integrals of creatine kinase-MB and C-reactive protein was 0.86. Daily measurement of serum C-reactive protein is useful in evaluating infarct size in patients with acute myocardial infarction who do not receive thrombolytic treatment. In patients treated with streptokinase C-reactive protein concentrations may be used to assess the success of thrombolysis.

Serum lipid changes in a one-year, multicenter, double-blind comparison of doxazosin and atenolol for mild to moderate essential hypertension.

Proatherogenic changes in serum lipid concentrations have been implicated as one of the major risk factors in the development of coronary artery disease. In a double-blind study, the new alpha 1-adrenoceptor inhibitor, doxazosin, was compared with atenolol for effects on the serum lipid profile. Ninety-six hypertensive patients were treated for up to 1 year with either doxazosin or atenolol once daily. There were statistically significant differences (p less than or equal to 0.01) between doxazosin and atenolol after 20 to 52 weeks of treatment in changes from baseline total triglyceride levels, high density lipoprotein (HDL) cholesterol levels and HDL/total cholesterol ratio. The percentage of change from baseline and the statistical significance of the difference between treatment groups were: total triglycerides, doxazosin -5.9%, atenolol +32.4% (p = 0.01); HDL cholesterol, doxazosin +7.2%, atenolol -5.6% (p = 0.007) and HDL/total cholesterol ratio: doxazosin +8.7%, atenolol -6.2% (p = 0.006). All mean changes were in favor of doxazosin therapy. In addition, doxazosin treatment beneficially decreased total serum cholesterol levels (-1.6%) compared with atenolol (+0.6%), although not to a significant degree. The differences were maintained in the cohort of 67 patients treated for a full year. The favorable change exerted by doxazosin on the lipid profile suggests that it may have a beneficial influence on the lipid risk factor. These results, together with the sustained decrease in blood pressure achieved for up to 1 year of therapy, suggest that doxazosin may reduce the risk of coronary artery disease in susceptible patients.

Thallium-201 washout in coronary artery disease using SPECT--a comparison with coronary angiography.

In this study, tomographic 201Tl washout analysis and coronary angiography were compared in 100 subjects. Seventeen subjects with healthy coronary arteries were used as reference material, on the basis of which the reference ranges for both the total washout of the heart muscle and the regional washout were determined. With angiography as the standard, this material yielded the following sensitivity values for total myocardial washout: 80% for three vessel proximal disease (n = 30), 64% for peripheral three vessel disease (n = 14), 66% for two vessel disease (n = 29) and 71% for single vessel disease (n = 17). Specificity in the reference group was 94%. Sensitivity values for regional washout were 83%, 93%, 59% and 71%, respectively. Stress ECG gave about 10% lower sensitivities. As far as sensitivity is concerned, however, visual assessment of tomographic images proved to be the best single method. In three patients, washout analysis was necessary to reveal evenly distributed ischemia and in seven cases it was essential in order to confirm an uncertain diagnosis; in other words, washout analysis had diagnostic value in 10 of the 100 patients.

Ultrasound imaging in diffuse thyroid disorders of children.

The diagnosis of diffuse thyroid disorders in children is based mainly on hormone and antibody determinations and a cytologic sample taken by aspiration biopsy. The cytologic sample is not always obtainable in small children or when the thyroid gland is not enlarged. Thyroid antibodies lead to diagnosis only in a proportion of cases. Gamma imaging is not recommended in children because of the radiation risk. The aim of this study was to demonstrate that ultrasound imaging can detect diffuse thyroid disorders in children. Ultrasound images were abnormal in 92% of all subjects; they were abnormal in 97% of cases with thyroiditis and in most cases ultrasound was diagnostic. With antibody determinations, only 60% of the cases of thyroiditis could be diagnosed. Ultrasound imaging--a risk-free method--should be included in the diagnostic investigation of thyroid disorders.

A long-term double-blind comparison of doxazosin and atenolol in patients with mild to moderate essential hypertension.

The efficacy and safety of doxazosin and atenolol were compared following once-daily administration for up to 1 year, with a minimum of 20 weeks' active treatment. According to response, patients received doxazosin 1-16 mg day-1 or atenolol 50-100 mg day-1. Mean daily doses at the final efficacy assessment (between 20 weeks and 1 year) were doxazosin 11.8 mg and atenolol 94.2 mg. Atenolol produced somewhat greater falls in blood pressure than doxazosin. The differences were statistically significant in the supine but not in the standing position. A small mean reduction in heart rate was produced by doxazosin whereas atenolol produced a marked bradycardia. Analysis of the same patient group at 20 weeks revealed similar overall profiles of activity except that atenolol produced greater falls in blood pressure than in the longer term analysis. Serum concentrations of HDL/total cholesterol ratio were raised in the doxazosin treatment group and lowered in the atenolol group. Triglyceride concentrations fell in the doxazosin group and rose in the atenolol group. Significant differences (P less than 0.001) were observed between treatment groups for these parameters, all differences being in favour of doxazosin. Pharmacokinetics of doxazosin, measured at steady state in 36 patients, showed dose-related plasma concentrations, a mean half-life of about 12 h and relatively low intersubject variation. The incidence of side-effects was slightly greater for patients in the doxazosin group. Drug-related side-effects were mostly mild to moderate in severity with no serious drug-related occurrences in either treatment group. No serious drug-related abnormalities in laboratory biochemistry and haematology tests were observed in either treatment group.

Supine and sitting maximal workload difference and response to long-term enalapril therapy in congestive heart failure.

Maximal workloads in supine and sitting bicycle stress tests were compared in 12 patients with congestive heart failure during long-term therapy with the vasodilator enalapril. The response to the therapy was observed with the supine and sitting bicycle stress tests and gated equilibrium ventriculography. The maximal workload was 68 W in the supine position and 84 W in the sitting position; the mean difference was 15 W. The difference was highly significant (P less than 0.001). Both the supine and sitting workloads were significantly higher (P less than 0.02 and P less than 0.05) in the enalapril group than in the placebo group. The findings in the gated equilibrium ventriculography were not significantly different between the two groups.

99mTc particle perfusion/99mTc aerosol ventilation imaging using a subtraction technique in suspected pulmonary embolism.

It is generally acknowledged that ventilation-perfusion mismatch is diagnostic of pulmonary embolism. Lung ventilation imaging with radioactive gases is a good method for the detection of pulmonary embolism, but it is not in widespread use because of the limited availability of 81mKr gas and the poor physical properties of 133Xe. Aerosols have been proposed, instead of gases for use in lung ventilation imaging. As perfusion and ventilation distributions may change very rapidly, the two imaging procedures should be done in rapid succession. The cheapest way to perform the combined perfusion-ventilation (Q/V) imaging is to use 99mTc-labelled macroaggregates and aerosols. In our method the perfusion imaging was done first, immediately followed by the ventilation imaging with 99mTc-labelled aerosols. A computer program was used to subtract the contribution of the perfusion from the combined Q/V image so that the pure ventilation image alone was obtained. The method was tested in 41 patients with suspected pulmonary embolism.

The use of radiolabelled monoclonal antibodies to human milk fat globule membrane antigens in antibody-guided tumour imaging, and administration of therapeutic dose of labelled antibody in wide-spread ovarian carcinoma. A preliminary report.

Monoclonal antibodies generated against human milk fat globule membrane antigens were used in antibody-guided tumour imaging and palliative therapy in a case of wide-spread ovarian carcinoma. Antibody III H 2, which previously has been shown to react with 100% of ovarian cystadenocarcinomas showed a strong reactivity with tissue sections obtained from the primary and metastatic tumours of the patient. Immunoglobulins were purified from mouse ascitic fluid containing III H 2 and labelled with 123I or 131I with the iodogen method. 80 MBq (2 mCi) of 123I-labelled antibody was given intraperitoneally in 500 ml of PBS and the uptake of radiolabel was followed daily with emission tomography. Radiolabel was mainly located in the peritoneal cavity; only a very low activity was seen in the thyroid gland and urinary bladder. A therapeutic dose consisting of 600 MBq (15 mCi) of 131I-labelled antibody was followed nine days later and the localization of the antibody was followed.

Emission tomography with 99mTc-pyrophosphate in the diagnosis of acute myocardial infarction.

Electrocardiograms (ECG) and enzyme criteria are usually used to confirm the diagnosis of acute myocardial infarction in the case of chest pain. However, ECG is not always diagnostic. Elevated enzyme values may be due to causes other than myocardial infarction. In uncertain cases, the ECG and enzyme criteria can be supplemented by emission tomography, performed with technetium pyrophosphate that will accumulate in the site of infarction. Twenty-nine patients with suspected acute myocardial infarction were studied with emission tomography. Of these 12 had acute transmural infarction. Both enzyme tests and ECG were diagnostic in only 7 of these 12 cases, 4 had positive enzyme tests but a nondiagnostic ECG and in one case neither enzymes nor ECG were diagnostic. In 11 patients the infarcted myocardial area was detected with emission tomography. Six patients had acute nontransmural infarction. Only 2 of these had positive emission tomography. The chest pain was not due to infarction in 11 patients. All these patients had negative emission tomography. The sensitivity of emission tomography was 92% and specificity 100% in transmural acute infarction. In nontransmural infarction the specificity was only 33%. Emission tomography is a valuable diagnostic tool. It may be the decisive method when ECG and enzymes are not diagnostic. Emission tomography also shows the localization and size of the infarcted area in the myocardium.

Ultrasonography in congenital hypothyreosis.

To our knowledge, ultrasonography has not so far been used as an additional source of information in the early screening for congenital hypothyreosis. This study demonstrated, firstly, that the normal neonatal thyroid gland could always be recognized by ultrasonography and, secondly, that in congenital hypothyreosis absence of thyroid tissue from the normal site could be detected by ultrasonography, whereas ectopic tissue in the tongue could not readily be identified. The findings may be useful in the diagnosis of congenital hypothyreosis.