Bicaudal D2 autoantibodies are highly specific for systemic sclerosis.

OBJECTIVE: Autoantibodies directed against the intracellular protein bicaudal D2 (BICD2) have been identified as a specific marker of systemic sclerosis (SSc). Since autoantibodies are of value in predicting disease onset and identifying meaningful clinical subsets, as well as having prognostic value, this study aimed to establish the prevalence of BICD2 autoantibodies (anti-BICD2) in a cohort of patients with connective tissue disease and healthy controls. METHOD: In this cross-sectional study, 363 patients with connective tissue disease (121 SSc, 141 systemic lupus erythematosus, 101 myositis, and 100 blood donors) were tested for the presence of anti-BICD2. All SSc patients were tested for specific anti-nuclear antibodies (ANAs), and clinical and laboratory associations were evaluated in the SSc patients, stratified by anti-BICD2 status. RESULTS: In the SSc cohort, 35 patients had autoantibodies directed against BICD2. The specificity of anti-BICD2 in SSc patients was 96.5%; however, the sensitivity was only 28.9%. Anti-BICD2 and centromere autoantibodies were present together in 91% of the anti-BICD2-positive SSc patients, and in none of the cases was anti-BICD2 the only antibody present. Anti-BICD2-positive patients had lower forced expiratory volume in 1 s (FEV1) (p = 0.01) and lower carbon monoxide transfer coefficient (KCO) (p = 0.01) than anti-BICD2-negative SSc patients, but they had higher forced vital capacity (p = 0.03). CONCLUSION: Autoantibodies against BICD2 were highly specific for SSc patients. Reduced FEV1 and KCO in anti-BICD2-positive patients may indicate that the presence of anti-BICD2 is associated with altered lung function in an unknown pathophysiological manner, which awaits further elucidation.

Characterization of mesoporous calcium phosphates from calcareous marine sediments containing Si, Sr and Zn for bone tissue engineering.

Calcium phosphates (CAPs) can be produced from either biologically sourced materials or mineral deposits. The raw materials impart unique properties to the CAPs due to innate trace amounts of elements that affect the crystal structure, morphology and stoichiometry. Using calcium carbonate (CaCO3) precursors derived from fossilized calcareous marine sediments (FCMSs), we have synthesized a novel class of CAP biomaterials, termed fm-CaPs, with defined Ca/P molar ratios of 1.4 and 1.7 using a wet synthesis method. Compared with commercially available CAP biomaterials, such as hydroxyapatite (HA) and beta-tricalcium phosphate (ß-TCP), fm-CaP1.7 had a biphasic composition consisting of an HA phase (in a hexagonal system) and a ß-TCP phase (in a rhombohedral crystalline system), which is desirable for the current design of bone substitutes, whereas fm-CaP1.4 consisted of an HA phase and a beta-dicalcium pyrophosphate phase (in a tetragonal system). These bioceramics exhibited a fringe structure of regular crystallographic orientation with well-ordered mesoporous channels. The FCMS raw material imparted trace amounts of silicon (Si), strontium (Sr) and zinc (Zn) to fm-CaPs; these are elements that are important for bone formation. The cyto-compatibility of these biomaterials and their effects on cellular activity were evaluated using osteoblast cells. Cell proliferation assays revealed no signs of cytotoxicity, whereas cells growth was equal to or better than HA and ß-TCP controls. The SEM analysis of the cell and material interactions showed good cell spreading on the fm-CaP materials that was comparable to ß-TCP and in vitro assays suggested robust osteogenic differentiation, as seen by increased mineralization (alizarin red) and upregulation of osteogenic gene expression. Our results indicate that fm-CaP1.7, in particular, has chemical, physical and morphological properties that make this material suitable for applications that promote bone tissue regeneration.

Epigenetic inheritance of transcriptional silencing and switching competence in fission yeast.

Epigenetic events allow the inheritance of phenotypic changes that are not caused by an alteration in DNA sequence. Here we characterize an epigenetic phenomenon occurring in the mating-type region of fission yeast. Cells of fission yeast switch between the P and M mating-type by interconverting their expressed mating-type cassette between two allelic forms, mat1-P and mat1-M. The switch results from gene conversions of mat1 by two silent cassettes, mat2-P and mat3-M, which are linked to each other and to mat1. GREWAL and KLAR observed that the ability to both switch mat1 and repress transcription near mat2-P and mat3-M was maintained epigenetically in a strain with an 8-kb deletion between mat2 and mat3. Using a strain very similar to theirs, we determined that interconversions between the switching- and silencing-proficient state and the switching and silencing-deficient state occurred less frequently than once per 1000 cell divisions. Although transcriptional silencing was alleviated by the 8-kb deletion, it was not abolished. We performed a mutant search and obtained a class of trans-acting mutations that displayed a strong cumulative effect with the 8-kb deletion. These mutations allow to assess the extent to which silencing is affected by the deletion and provide new insights on the redundancy of the silencing mechanism.

Relationships between serum thyrotropin, serum free thyroxine (T4), and 3,5,3'-triiodothyronine (T3) and the daily T4 and T3 production rates in euthyroid patients with multinodular goiter.

Serum TSH, as measured by a sensitive assay, and serum free T4 and T3, as measured by an ultrafiltration technique, were compared in 14 euthyroid patients with multinodular goiter and 14 normal subjects. T4 and T3 turnover studies also were performed, using the single injection, noncompartmental approach. The goitrous patients had serum free T3 levels within the normal range, but their median serum T3 level was increased compared to that in the normal subjects [goitrous patients, 5.48 pmol/L (range, 4.41-9.03); normal subjects, 4.12 pmol/L (range, 2.58-5.78); P less than 0.01]. The T3 production rate (PR) also was elevated in the patients (median, 39.4 nmol/day X 70 kg; range, 28.7-70.5) compared to that in the normal subjects 31.1 nmol/day X 70 kg; range, 24.4-45.2); P less than 0.05). No differences were found between the two groups with regard to serum free T4 levels or T4 PRs. Serum TSH levels in the patients were reduced (median, 0.20 mU/L; range, less than 0.05-1.6) compared to those in normal subjects (1.8 mU/L; range, 0.36-5.1; P less than 0.01). A significant inverse correlation was found between serum TSH levels and free T3 levels (r = 0.70; P less than 0.001), whereas serum TSH did not correlate with serum free T4 or the PR of T4 or T3. Our data suggest that clinically and biochemically euthyroid patients with multinodular goiter have slight T3 hyperproduction, and TSH secretion in the patients studied was more closely related to serum free T3 levels than to serum free T4 levels or the T3 or T4 PR.

Simultaneous turnover studies of thyroxine, 3,5,3' and 3,3',5'-triiodothyronine, 3,5-, 3,3'-, and 3',5'- diiodothyronine, and 3'-monoiodothyronine in chronic renal failure.

The present study evaluates the sequential extra-thyroidal monodeiodination of thyroid hormones through tri-, di-, and monoiodothyronines in chronic renal failure (CRF) in man. Simultaneous turnover studies of T4, T3, rT3, 3,5-diiodothyronine (3,5-T2), 3,3'-T2, 3',5'-T2, 3'5'-T2, and 3'-monoiodothyronine (3--T1) were conducted in six patients with CRF (creatinine clearance, 9-18 ml/min) using the single-injection, noncompartmental approach. Serum levels of T4, T3, and 3,5-T2 were reduced to two thirds of control levels (P less than 0.05), whereas serum rT3 and 3,3'-T2 levels were reduced to a minor degree. Serum 3'-5'-T1 was doubled (p less than 0.05). The MCRs of T4, rT3, and 3',5'-T2 were enhanced to 168%, 127%, and 187% of normal (P less than 0.05), respectively, whereas those of T3, 3,5-T2, 3,3'-T2, and 3'-T1 were unaffected. The mean production rates (PRs) of the iodothyronines in CRF were as follows (CRF vs. control values, expressed as nanomoles per day/70 kg): T4, 119 vs. 125; T3, 26 vs. 44 (P less than 0.01); rT3, 49 vs, 48; 3,5-T2, 3.5 vs. 7.2 (P less than 0.001); 3,3'-T2, 25 vs. 35 (P less than 0.01); 3',5'-T2, 25 vs. 14 (P less than 0.01); and 3'-T1, 39 vs. 30. Previous studies have demonstrated reduced phenolic ring (5'-) deiodination of T4 in CRF, which is supported by the present finding of unaltered PR of T4 and reduced PR of T3. In contrast the 5'-deiodination of T3 leading to the formation of 3,5-T2 was found unaffected by CRF, since the conversion rate (CR) of T3 to 3,5-T2 (PR 3,5-T2/PR T3) was unaltered (16% vs. 15% in controls). The tyrosylic ring (5-) deiodination of T4 to rT3 was unaffected in patients with CRF, the CR being 42% vs. 40% in controls, in contrast to an enhanced CR of rT3 to 3',5'-T2 (53% vs. 29%, P less than 0.01), which also is a 5-deiodination step. In conclusion, our data show that CRF profoundly changes the kinetics of all iodothyronines studied. Furthermore, our data are compatible with the existence of more than one 5'-deiodinase as well as more than one 5-deiodinase in man.

The extrathyroidal conversion of 3,5,3'-triiodothyronine to 3,5-diiodothyronine in patients with liver cirrhosis.

Simultaneous kinetic studies of 3,5-diiodothyronine (3,5-T2) and T3 were performed in 8 patients with biopsy proven cirrhosis and in 15 healthy subjects using the single injection, noncompartmental approach. The following T3 kinetic data were obtained in patients with cirrhosis and normal subjects (mean +/- SD): serum T3 (nmol/liter) 1.27 +/- 0.30 vs. 1.79 +/- 0.28 (P less than 0.001); MCR [liters X day-1 X (70 kg)-1] 22.9 +/- 5.3 vs. 26.7 +/- 4.4 (P less than 0.10); production rate [nmol X day-1 X (70 kg)-1] 29.0 +/- 9.6 vs. 47.7 +/- 9.0 (P less than 0.001). In patients with cirrhosis serum 3,5-T2 levels were reduced to 58 +/- 38% of those found in normal subjects (P less than 0.02). The MCR was unaffected, 125 +/- 85%, whereas the production rate was reduced to 57 +/- 26% (P less than 0.005). The conversion rate from T3 to 3,5-T2 was unaltered, 96 +/- 34% of that found in normals. It is concluded that reduced serum levels of 3,5-T2 in cirrhosis are due to a diminished amount of substrate, T3, and not to decreased 3'-deiodination of T3 or to an increase clearance of 3,5-T2.

Effect of propranolol on extrathyroidal metabolism of thyroxine and 3,3',5-triiodothyronine evaluated by noncompartmental kinetics.

Kinetic studies of T4 and T3 using a noncompartmental approach were performed in seven patients with pretreatment severe hypothyroidism maintained on L-T4 replacement. Each subject received a combined tracer dose of labeled T4 and T3 as an iv bolus before and during peroral treatment with propranolol. Serum T4 was unchanged, while a significant decrease of 13% was found in serum T3. The disposal rates (DR) of T4 and T3 decreased significantly, and the ratio between the DR off T3 and the DR of T4, the conversion rate, was significantly reduced during propranolol treatment. The decrease in the DR of T4 suggests a reduction in the bioavailability of L-T4 during propranolol, possibly due to a decrease in intestinal absorption. The decrease in the conversion rate indicates a reduced extrathyroidal conversion of T4 to T3 during propranolol treatment.

The extrathyroidal effect of D,L-propranolol on 3,3',5'-triiodothyronine, 3',5'-diiodothyronine, 3,3'-diiodothyronine, and 3'-monoiodothyronine kinetics.

The effect of D,L-propranolol (80 mg daily) on the peripheral monodeiodination of rT3, 3',5'-diiodothyronine (3',5'-T2), 3,3'-diiodothyronine (3,3'-T2), and 3'-monoiodothyronine (3'-T1) was studied in seven out-patients with severe pretreatment hypothyroidism. The patients were maintained euthyroid on a constant L-T4 replacement therapy. A bolus injection technique was used; MCR, production rate (PR), and conversion rate were determined using a noncompartmental kinetic model. During D,L-propranolol, serum rT3 and 3',5'-T2 increased (P less than 0.02), and 3,3'-T2 seemed to decrease. The MCRs of rT3, 3',5'-T2, and 3,3'-T2 (P less than 0.02) decreased during drug treatment. The MCR and PR of 3'-T1 were reduced, albeit not significantly (P less than 0.10). The PR of 3,3'-T2 was reduced (P less than 0.02), whereas the PRs of rT3 and 3',5'-T2 were unaltered. The conversion rate of rT3 to 3',5'-T2 was unaltered. No changes were seen in the apparent distribution volumes of the iodothyronines studied. The results are compatible with the assumption that D,L-propranolol, or a metabolite thereof, inhibits the 5'-deiodination of all of the iodothyronines.

Simultaneous measurement of 3,5-diiodothyronine and 3,5,3'-triiodothyronine turnover kinetics in euthyroid hyperthyroid, and hypothyroid subjects.

Simultaneous kinetic studies of 3,5-diiodothyronine (3,5-T2) and T3 were performed in 15 healthy controls (8 men and 7 women), 7 hyperthyroid patients (2 men and 5 women), and 6 hypothyroid women using the single injection, noncompartmental approach. The serum concentrations (picomoles per liter), MCRs (liters . day-1 . (70 kg)-1), and production rates (PRs; nmol . day-1 . (70 kg)-1) of 3,5-T2 in healthy men and women were (mean +/- SD): 100 +/- 23 vs. 80 +/- 23 (P = NS), 59 +/- 31 vs. 123 +/- 58 (P less than 0.025), and 5.6 +/- 1.9 vs. 9.1 +/- 2.6 (P less than 0.02). The conversion rate (CR) of T3 to 3,5-T2 was 12.0 +/- 3.8% in men compared to 18.5 +/- 3.7% in women (P less than 0.01). Serum 3,5-T2 levels in five mildly hyperthyroid women were elevated to 123 +/- 33 pmol/liter (P less than 0.05), whereas the MCR and PR were unchanged. However, two hyperthyroid men with more pronounced elevation of serum T3 had enhanced PRs (26.9 and 23.9 nmol . day-1 . (70 kg)-1). The CR in hyperthyroid women was significantly reduced to 5.6 +/- 2.9% (P less than 0.001). The serum levels, MCR, and PR of 3,5-T2 in hypothyroid women were: 58 +/- 25 pmol/liter (P = NS), 71 +/- 52 liters . day-1 . (70 kg)-1 (P = NS), and 3.4 +/- 2.4 nmol . day-1 . (70 kg)-1 (P less than 0.005). The CR was enhanced to 34.8 +/- 15.7% (P less than 0.05). Our data demonstrate that in euthyroid subjects, approximately 15% of T3 is deiodinated to 3,5-T2, and this 5'-deiodination of T3 is influenced by thyroid function.

Kinetic studies of thyroxine, 3,5,3'-triiodothyronine, 3,3,5'-triiodothyronine, 3',5'-diiodothyronine, 3,3'-diiodothyronine, and 3'-monoiodothyronine in patients with liver cirrhosis.

Turnover studies of T4, T3, rT3, 3',5'-diiodothyronine (3',5'-T2), 3,3'-diiodothyronine (3,3'-T2), and 3'-monoiodothyronine (3'-T1) were performed in 10 patients with alcoholic cirrhosis of the liver and 9 euthyroid, healthy controls using the single injection, noncompartmental approach. The kinetics of all 6 iodothyronines were studied in the same individuals. A newly developed, simple and reproducible gel separation technique, followed by antibody extraction, was used for the quantitation of tracer in serum. Serum T4, T3, and 3,3'-T2 levels were reduced in patients with liver cirrhosis, whereas serum rT3 and 3',5'-T2 levels were increased, Serum 3'-T1 levels were unaltered. A general tendency toward reduced MCRs was observed. The following median MCRs (liters per day per 70 kg BW) were found (cirrhotics vs. controls): T4, 1.13 vs. 1.19 (P = NS); T3, 16 vs. 20 (P less than 0.05); rT3, 81 vs. 147 (P less than 0.01); 3',5'-T2, 131 vs. 279 (P less than 0.01); 3,3'-T2, 533 vs. 1116 (P less than 0.01); and 3'-T1, 375 vs. 539 (P less than 0.05). The production rates (nanomoles per day per 70 kg BW) of T4, rT3, and 3,'5'-T2 were not significantly altered in patients with cirrhosis (cirrhotics vs. controls): 100 vs. 117, 47.5 vs. 52.0, and 14.5 vs. 13.9, respectively. In contrast, the following pronounced reductions in production rates of T3, 3,3'-T2, and 3'-T1 were found: 19.1 vs. 38.8 (P less than 0.01), 13.2 vs. 36.8 (P less than 0.01), and 15.7 vs. 28.6 (P less than 0.05), respectively. Assuming that thyroidal secretion contributes little rT3 and 3',5'-T2, the conversion rates from T4 to rT3 and further to 3',5'-T2 were calculated and found to be unaffected in patients with liver cirrhosis (48% vs. 34% in controls and 34% vs. 26% in controls, respectively). No tendency toward major changes in the activity of the nondeiodinative metabolic pathways was observed. In conclusion, our data show that liver cirrhosis profoundly changes the kinetics of all iodothyronines studied. Further, the 5-deiodination of T4 and rT3 is unaffected in patients with liver cirrhosis. In contrast, a general inhibition of the 5'-deiodinations seems to exist in patients with liver cirrhosis. Thus, our data are compatible with the existence of a common 5-deiodinase and a common 5'-deiodinase for the sequential deiodination of the iodothyronines in man.

Urinary excretion of free and conjugated 3',5'-diiodothyronine and 3,3'-diiodothyronine.

RIAs for the estimation of 3',5'-diiodothyronine (3',5'-T2) and 3,3'-diiodothyronine (3,3'-T2) in human urine have been established. The urinary excretion of both glucuronide and sulfate conjugates of T2 and of T4, T3, and rT3 were estimated by means of enzymatic deconjugation. In healthy controls, the mean excretion (picomoles per 24 h) of free T4 was 1820, that of free T3 was 813, that of free rT3 was 77, that of free 3',5'-T2 was 13, and that of free 3,3'-T2 was 674. The total excretion of free and conjugated T4 was 2941, that of T3 was 1283, that of rT3 was 791, that of 3',5'-T2 was 709, and that of 3,3'-T2 was 2688. Significant amounts of sulfated T4 and T3 could not be demonstrated, amounts of sulfated T4 and T3 could not be demonstrated, whereas the excretion of sulfated rT3 was higher than that of glucuronidated rT3 (P less than 0.001). In contrast, glucuronidated and sulfated 3',5'-T2 as well as glucuronidated and sulfated 3,3'-T2 were found in the urine in equal amounts. In hyperthyroidism, the excretions of free and glucuronidated iodothyronines were increased, whereas the increase of the excretions of sulfated iodothyronines were less pronounced, only reaching statistical significance for 3,3'-T2 (P less than 0.02). In hypothyroidism, the excretions of both free, glucuronidated and sulfated iodothyronines were reduced. Significant amounts of sulfated T4 and T3 could not be demonstrated in urine from hyperthyroid or hypothyroid patients. Our data demonstrate that the amounts of free iodothyronines excreted in the urine vary considerably, suggesting active renal handling. The amounts of urinary glucuronidated and sulfated conjugates of the different iodothyronines studied vary considerably and are affected by thyroid function.

Thyroid-stimulating immunoglobulins in Hashimoto's thyroiditis measured by radioreceptor assay and adenylate cyclase stimulation and their relationship to HLA-D alleles.

The relationship between thyroid-stimulating immunoglobulins, measured by both radioreceptor assay and adenylate cyclase stimulation, and the HLA alleles was studied in 41 patients with Hashimoto's thyroiditis. TSH binding-inhibiting immunoglobulins (TBII) were detected in 9 (22%) patients, and human thyroid adenylate cyclase-stimulating immunoglobulins (HTACS) were found in 21 (51%) patients. Only 2 patients were positive in both assays, and an inverse relationship was observed between TBII and HTACS. In the 21 HTACS-positive patients, HLA-Dw5 was only found in 1 subject, compared to 8 of the 20 HTACs-negative patients (P less than 0.01), while 4 of the 9 TBII-positive patients had HLA-Dw5 compared to 5 of the 32 TBII-negative subjects (P = -0.09). No significant relations were observed between the presence of HTACS or TBII and HLA-Dw3 or HLA-B8. It is concluded, that TBII and HTACS are produced independently in Hashimoto's thyroiditis, and that the production of these autoantibodies seems to be related to the HLA-D region in this disease.

The effects of phenytoin (diphenylhydantoin) on the extrathyroidal turnover of thyroxine, 3,5,3'-triiodothyronine, 3,3',5'-triiodothyronine, and 3',5'-diiodothyronine in man.

The extrathyroidal metabolism of T4, T3, rT3, and 3',5'-diiodothyronine (3',5'-T2) was studied before and after treatment with 350 mg phenytoin (DPH) daily for 14 days in six hypothyroid patients receiving constant L-T4 replacement. The total and free serum concentrations of the four iodothyronines were reduced by approximately 30% during DPH treatment, whereas the free fractions in serum were unaltered. Concomitantly, serum TSH increased 137% (P less than 0.02). The production rate (PR) of T4 decreased 16% (P less than 0.005), indicating decreased intestinal absorption (bioavailability) of oral L-T4 during DPH treatment. The fractional rate of 5'-deiodination of T4 to T3 increased from 27% to 31% (P less than 0.05), whereas the rate of 5-deiodination of T4 to rT3 decreased from 45% to 25% (P less than 0.05). The urinary excretion of free and conjugated T4 was 2.3% of the T4 PR and was unaffected by DPH. Thus, the amount of T4 metabolized through nondeiodinative pathways apart from urinary excretion increased from 25% to 44% (P less than 0.05). The apparent distribution volume (Vd) of T4 increased (P less than 0.05), whereas the pool size was unchanged. The PR of T3 did not change during DPH treatment, nor did the mean transit time or the cellular clearance. The rT3 PR was reduced by 54% (P less than 0.02) during DPH treatment. Concomitantly, the transit time increased 10-fold (P less than 0.05), whereas Vd and pool size increased 5-fold (P less than 0.01 and P less than 0.05, respectively). The turnover of 3',5'-T2, in contrast to that of the other iodothyronines, did not change significantly during DPH treatment. T3 formation from T4 was measured in liver microsomal fractions from rats treated for 8 days with DPH and was almost identical to that in untreated animals. The data demonstrate that DPH in therapeutic concentrations did not affect serum protein binding of the iodothyronines. DPH reduced the intestinal absorption of T4 and increased the nondeiodinative metabolism of T4. The resulting decrease in total and free serum T4 and T3 was associated with an increase in serum TSH, demonstrating reduced negative feedback on the pituitary. Our data do not support the assumption that DPH induces increased hepatic deiodinating enzyme activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of mianserin in neuroleptic-induced parkinsonism.

It has been proposed that serotonin (5-HT) antagonists counteract neuroleptic-induced extrapyramidal symptoms by disinhibition of dopamine activity. The effects of the 5-HT antagonist mianserin, the anticholinergic drug procyclidine and placebo were evaluated in 16 psychiatric patients with chronic neuroleptic-induced parkinsonism in a double-blind cross-over trial. The patients received each drug in random order in 3-week periods separated by washout periods of 2 weeks. The effect of mianserin did not significantly differ from that of placebo, while parkinsonian symptoms were significantly reduced during treatment with procyclidine (P less than 0.05). Although mianserin was ineffective in chronic neuroleptic-induced parkinsonism, it cannot be excluded that 5-HT antagonists may be effective in the treatment of acute extrapyramidal side effects.

Serum lipids in hyper- and hypothyroidism before and after treatment.

Total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides (TG) and apoprotein A (Apo A) were determined in serum from 21 hyperthyroid patients and 11 hypothyroid patients before and after treatment to euthyroid state. The above-mentioned components were also determined in a reference population. In the hyperthyroid group the concentration of total cholesterol and low density lipoprotein-cholesterol increased significantly upon treatment. High density lipoprotein also increased except for 9 patients also receiving propranolol. The ratio between high density lipoprotein-cholesterol and total cholesterol decreased in the patients receiving propranolol. In the hypothyroid group the values after treatment decreased significantly for cholesterol, high density lipoprotein-cholesterol and low density lipoprotein-cholesterol. The ratio between high density lipoprotein-cholesterol and total cholesterol was unchanged.

Microalbuminuria in type 2 diabetic patients: a prospective follow-up study.

We have studied 46 patients, 30 men and 16 women, with type 2 (non-insulin-dependent) diabetes in a follow-up period of 6-52 months (mean 30 months). The patients were consecutively entered in the study from the out-patient diabetic clinic. None had urinary tract infections nor proteinuria at entry. Investigations were done every 3 months during the first year and after that every 6 months. At entry 16 patients (35%) had microalbuminuria and a further 16 patients developed microalbuminuria and 16 proteinuria. The systolic blood pressure was higher in men with microalbuminuria compared to men without microalbuminuria. The glomerular filtration rate decreased with time for patients with microalbuminuria without change in plasma creatinine. The C-peptide concentration was higher in the hypertensive patients compared to non-hypertensive and the same was found for the triglyceride concentration. During the observation period the various complications increased in frequency (retinopathy, cardiomyopathy, neuropathy, angiopathy and hypertension) without significant relation to the presence of microalbuminuria or proteinuria. During the observation period nine patients died mainly due to cardiovascular events.

Microalbuminuria in type 2 diabetic patients: a cross-sectional study of frequency, sex distribution and relation to hypertension.

We studied 112 type 2 diabetic patients. Fourteen patients had frank proteinuria, and 37 of the remaining 98 had microalbuminuria which was more frequent in men than in women (P < 0.02). Hypertension was found in 47 of the patients, equally distributed between sexes. Male diabetics with microalbuminuria had higher systolic blood pressure than diabetics without microalbuminuria (P < 0.02). Body mass index was higher in both sexes with hypertension compared to patients without hypertension. In the hypertensive men plasma C-peptide values were higher compared to patients without hypertension (P < 0.01) irrespective of the presence of microalbuminuria. A positive correlation between blood pressure and C-peptide was found (P < 0.01) in the men. We suggest that gender should be taken into account in the analysis and interpretation of microalbuminuria in type 2 diabetes.

[Incest and sexual abuse. A study among patients at a hospital for neuroses, Montebello]. / Incest og seksuelt misbrug. En undersøgelse blandt patienter på neurosehospitalet Montebello.

A cross-sectional investigation on a day chosen at random i autumn 1987 in the Hospital for Neuroses, Montebello, Elsinore, revealed that a total of 25% of the female patients treated on that date had previously been the victims of incest (8.7%) or sexual abuse (17.3%). Of these, the great majority, 19 out of 23 (82%) had been abused prior to the age of 18 years. One out of 15 male patients (7%) had been the victim of previous sexual abuse. Approximately one third of the sexually abused women had been abused by more than one person. The incident had been reported to the police on one occasion only. In addition, previous incest/sexual abuse was presumed where further 10% of the female patients were concerned, on the basis of the opinions formed by the therapists from the clinical pictures and the case histories. In approximately half of the cases, the secrecy concerning the abuse was broken in the course of the psychotherapeutic process and it is concluded that frankness knowledge and courage on the part of the therapist are essential in order to establish sufficiently differentiated psychotherapeutic treatment and that increased knowledge about the problem in society will presumably exert a prophylactic effect.

[Contraception with implanted gestagens]. / Kontraception ved implanterede gestagener.

PIP: 990 women, 18-35 years of age, underwent subcutaneous silastic implants of levonorgestrel (N = 492) and norgestrionone (N = 498). These patients were compared to 402 women who used the Copper-T 200 IUD. Control examinations were performed 1,3,6,9, and 12 months after contraceptive use began. There were 3 pregnancies in the levo-norgestrel group which occurred during the first 4 months of contraceptive use. There were 17 pregnancies in the norgestrionone group, which occurred toward the end of the contraceptive use period. Menstrual bleeding disorders were the most frequent reasons for discontinuing subcutaneous implant use and occurred more often among the levo-norgestrel patients (generally metrorrhagia and menorrhagia). There were 4 pregnancies among the IUD patients. The continuation rate for the levo-norgestrel group was 74.6%; for the norgestrionone users 79.9%; and for the IUD users 81.1%. Anemia and changes in blood pressure were not observed among the subcutaneous implant patients. IUD patients showed no weight gain, while the subcutaneous implant patients gained on an average 1 kg.^ieng

Mesodermal and neural crest derived ovine tibial and mandibular osteoblasts display distinct molecular differences.

Mandibular osteoblasts originate from the neural crest and deposit bone intramembranously, mesoderm derived tibial osteoblasts by endochondral mechanisms. Bone synthesized by both cell types is identical in structure, yet functional differences between the two cell types may exist. Thus, both matched juvenile and adult mandibular and tibial osteoblasts were studied regarding their proliferative capacity, their osteogenic potential and the expression of osteogenic and origin related marker genes. Juvenile tibial cells proliferated at the highest rate while juvenile mandibular cells exhibited higher ALP activity depositing more mineralized matrix. Expression of Hoxa4 in tibial cells verified their mesodermal origin, whereas very low levels in mandibular cells confirmed their ectodermal descent. Distinct differences in the expression pattern of bone development related genes (collagen type I, osteonectin, osteocalcin, Runx2, MSX1/2, TGF-ß1, BAMBI, TWIST1, ß-catenin) were found between the different cell types. The distinct dissimilarities in proliferation, alkaline phosphatase activity, the expression of characteristic genes, and mineralization may aid to explain the differences in bone healing time observed in mandibular bone when compared to long bones of the extremities.