Current structures of cardiac centers

The "Working Group for Congenital Heart Surgery and Pediatric Heart Surgery" of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) has analysed and recommended structures for congenital heart surgery departments in Germany. The document was worked out according to a similar paper approved earlier by the European Association for Cardio-thoracic Surgery (EACTS). The "Working Group" unifies the majority of cardiac surgeons involved in congenital heart surgery in Germany. Current structures of cardiac centers vary. Therefore the aim of this document is to elucidate additional structural needs for both highly specialized institutions and those for standard care. Specialized centers should allow for treatment of newborns and adult patients with congenital heart disease, include implementation of assist devices and transplantation, possess research facilities and ensure highest standards of education and training. Standard care units do not necessarily need to cater for the above mentioned spectrum. However, the evaluation of quality of care should be given priority in all centers involved in care of patients with congenital heart disease. Data acquisition and transfer must be guaranteed to both the GSTCVS and EACTS in order to ensure national and international comparison of surgical results. This may also give further guidance for improved patient care.     

Thyroid function differently affects serum cystatin C and creatinine concentrations

Cystatin C (Cys C) is a cysteine protease inhibitor produced at a constant rate by nucleated cells, filtered through the glomerular membrane and reabsorbed by kidney tubular cells. Aim of this cross-sectional and longitudinal study was to assess serum Cys C and creatinine (Crea) concentrations in thyroid dysfunction. One hundred and eighty-one patients, 26 with untreated non-toxic nodular goiter, 58 with hyperthyroidism, 31 on L-T4 suppressive therapy for non-toxic nodular goiter, 35 with short-term hypothyroidism after L-T4 withdrawal to perform whole body scan for thyroid cancer, 11 with long-term hypothyroidism due to chronic autoimmune thyroiditis and 20 patients with mild hypothyroidism were enrolled in the study. Fifty-seven age- and sex-matched normal subjects served as controls. Serum Cys C, Crea, free T4 (FT4), FT3 and TSH were assessed. Thirty hyperthyroid patients and 35 short-term hypothyroid patients were followed prospectively until euthyroidism was reached by methimazole or L-T4 therapy. The cross-sectional study showed that mean serum Crea concentrations were significantly reduced in overt hyperthyroid or subclinical hyperthyroid patients, while it was increased in overt hypothyroid patients, but not in mild hypothyroidism. Conversely, serum Cys C levels were significantly increased in overt hyperthyroid patients compared to controls (p<0.05), and significantly decreased in short-term, long-term and mild hypothyroids (p<0.05, p<0.05, p<0.01, respectively). However, 36 (62%) hyperthyroid patients and 50 (76%) hypothyroid patients had normal serum Cys C values. In the prospective study, restoration of euthyroidism by either methimazole or L-T4 therapy was associated with normalization of mean serum Cys C concentrations. In conclusion, thyroid dysfunction affects serum Cys C concentration, possibly influencing the production rate of the protein. However, the observation that hyper- or hypothyroid patients have normal serum Cys C levels limits its use as a marker of peripheral thyroid hormone effect.     

Undetectable inferior petrosal sinus levels of PTH-related peptide (PTHrP) in patients with ACTH-dependent Cushing's disease

PTH-related peptide (PTHrP), a member of the PTH family, is widely expressed in foetal and adult tissues, and it has been found in benign and malignant tumors, including GH and PRL-secreting adenomas. Conflicting data are reported in literature on serum PTHrP concentrations in patients with Cushing's disease. The aim of the present study was to further evaluate peripheral and inferior petrosal sinus (IPS) serum PTHrP concentrations before and after CRH, in a group of consecutive patients with ACTH-dependent Cushing's disease. Nine patients with active ACTH-dependent Cushing's disease (8 women and 1 man, age +/- SD 41 +/- 13 yr) were submitted to peripheral and IPS sampling under fluoroscopic control before and after iv administration of CRH. All patients were subsequently submitted to transsphenoidal surgery and an ACTH-secreting microadenoma was found in all cases. In all patients, serum IPS and peripheral ACTH measurement were in keeping with the diagnosis of ACTH-dependent Cushing's disease. Serum PTHrP concentrations before and after CRH stimulation were below the sensitivity limit of the assay in all samples, and no gradient between IPS and peripheral sampling was observed. Our data, combined with others reported in literature, indicate that PTHrP release by ACTH-secreting tumors is not a common occurrence. Therefore, we conclude that IPS and peripheral PTHrP are of little clinical usefulness.     

Thyroid vascularity is increased in patients with active acromegaly

OBJECTIVE: To determine whether acromegalic patients have increased thyroidal vascularity and blood flow on colour flow Doppler sonography (CFDS). DESIGN: Prospective study of consecutive patients. PATIENTS: Twenty-four acromegalic patients (11 men, 13 women, age 49 +/- 9 years); 38 patients with nontoxic goitre (NTG; 12 men, 26 women, age 50 +/- 7 years); 36 normal subjects (controls; 16 men, 20 women, age 46 +/- 9 years). Among acromegalic patients, 10 had active, untreated disease (Acro-U), seven were in remission after surgery (Acro-R), seven had active disease under treatment with somatostatin analogues (SMSa) (Acro-SA) (Sandostatin LAR, 20 mg, every 28 days). MEASUREMENTS: CFDS pattern and intrathyroidal peak systolic velocity (PSV) were determined by a colour Doppler system with a 7.5-MHz linear transducer. PSV measurements were made at the level of the intrathyroidal arteries (normal values 3.8 +/- 1.0 cm/s). Thyroid volume was calculated by the ellipsoidal model. Assays included measurements of serum GH, IGF-I, free T4, free T3, TSH, antithyroglobulin (anti-Tg) and antithyroperoxidase (anti-TPO) antibodies, TSH-receptor antibodies (TRAb). RESULTS: Serum GH (+/- SD) and IGF-I (+/- SD) levels were: Acro-U: GH 26 +/- 31 microg/l, IGF-I 783 +/- 299 microg/l; Acro-SA: GH 15 +/- 25 microg/l, IGF-I 366 +/- 212 microg/l; Acro-R: GH 1.3 +/- 1.0 microg/l, IGF-I 241 +/- 99 microg/l. To convert values for serum GH to mU/l multiply by 2.6; to convert values for serum IGF-I to nmol/l multiply by 0.13075. All controls had CFDS pattern 0 (absent vascularity or minimal spots); among NTG patients, 36 had pattern 0 and two had pattern I (parenchymal blood flow with patchy uneven distribution). Five patients with acromegaly had pattern 0, 12 had pattern I and seven pattern II (mild increase of colour flow Doppler signal with patchy distribution). Among the five acromegalic patients with pattern 0, three were Acro-R and two were Acro-SA. Among patients with pattern I, six were Acro-U, two were Acro-SA and four were Acro-R. Among patients with pattern II, four were Acro-U and three Acro-SA; two patients of the latter group had elevated serum IGF-I under SMSa treatment. Intrathyroidal PSV was 3.8 +/- 1.0 cm/s in controls, 4.0 +/- 1.1 cm/s in NTG, 7.4 +/- 0.8 cm/s in Acro-U, 4.9 +/- 1.3 cm/s in Acro-SA treatment and 4.5 +/- 1.0 in Acro-R. (Acro-U vs. Acro-SA, P = 0.0003; vs. Acro-R, Controls, or NTG, P < 0.0001). PSV values in Acro-SA were higher than those observed in NTG or controls (P = 0.05, P = 0.01, respectively); PSV values in Acro-R did not differ from those in NTG or controls. Intrathyroidal PSV values were correlated with serum IGF-I (r = 0.73, P < 0.0001) and, although less strongly, GH levels (r = 0.54, P = 0.01). Goitre was present in 19 of 24 patients; diffuse in three and nodular in 16. Thyroid function was normal in all subgroups of acromegalic patients. Anti-Tg, anti-TPO antibodies and TRAb were negative in all subjects. CONCLUSIONS: Patients with active acromegaly have increased intrathyroidal blood flow (colour flow Doppler sonography pattern II, increased peak systolic velocity values); this was not observed in the large majority of patients under treatment with somatostatin analogues and in any patient in remission. Accordingly, colour flow Doppler sonography and peak systolic velocity measurements may be considered an additional useful peripheral parameter for rapid assessment of the activity of acromegaly.     

The significance of HLA-DRB1 matching on clinical outcome after HLA-A, B, DR identical unrelated donor marrow transplantation

Despite matching for serologically defined HLA-A, B, DR antigens, acute graft-versus-host disease (GVHD) is a major complication contributing to increased morbidity and mortality in patients who undergo marrow transplantation from unrelated donors. The extent to which unrecognized mismatching for alleles that encode DR1-DR18 contribute to the increased risk of acute GVHD and overall survival is unknown. We analyzed 364 patients and their HLA-A, B, DR serologically matched donors to determine whether molecular typing of DRB1 alleles can allow more accurate donor/recipient matching and thereby improve clinical outcome after marrow transplantation. DRB1 alleles were typed by sequence-specific oligonucleotide probe hybridization methods. Selected alleles were confirmed by DNA sequencing. Of the 364 pairs, 305 were matched and 59 were mismatched for DRB1. The probability of moderate to severe acute GVHD was .48 for the matched and .70 for the mismatched patients. Compared with mismatched patients, the estimated relative risk (RR) of GVHD for matched patients was .58 (95% confidence interval [CI], .40 to .85). DRB1 matching decreased the risk of transplant- related mortality (RR, .66; 95% CI, .44 to .97) and was associated with decreased overall mortality (RR, .71; 95% CI, .51 to 1.0). Therefore, matching DRB1 alleles of the donor and recipient decreases the risk of acute GVHD and improves survival after unrelated marrow transplantation. These results indicate that prospective matching of patients and donors for DRB1 alleles is warranted.     

Interferon-inducible protein 10, monokine induced by interferon gamma, and interferon-inducible T-cell alpha chemoattractant are produced by thymic epithelial cells and attract T-cell receptor (TCR) alphabeta+ CD8+ single-positive T cells, TCRgammadelta+ T cells, and natural killer-type cells in human thymus

Strong reactivity for interferon-inducible protein 10 (IP-10), monokine induced by interferon gamma (Mig), and interferon-inducible T-cell alpha chemoattractant (I-TAC) was found in epithelial cells mainly localized to the medulla of postnatal human thymus. The CXC chemokine receptor common to the 3 chemokines (CXCR3) was also preferentially expressed in medullary areas of the same thymuses and appeared to be a property of 4 distinct populations: CD3+ T-cell receptor (TCR) alphabeta+ CD8+ single-positive (SP) T cells, TCRgammadelta+ T cells, natural killer (NK)-type cells, and a small subset of CD3+(low) CD4+ CD8+ TCRalphabeta+ double-positive (DP) T cells. IP-10, Mig, and I-TAC showed chemoattractant activity for TCRalphabeta+ CD8+ SP T cells, TCRgammadelta+ T cells, and NK-type cells, suggesting their role in the migration of different subsets of mature thymocytes during human thymus lymphopoiesis.