Hemodynamics of venous cuff interposition in prosthetic arteriovenous fistulas for hemodialysis

PURPOSE: The durability of prosthetic arteriovenous fistulas (AVF) for hemodialysis is jeopardized by thrombotic occlusions due to intimal hyperplastic stenoses. In arterial reconstructive surgery, peripheral arterial bypasses with prosthetic material benefit from a venous cuff at the distal anastomosis. Therefore, a study was performed to assess the effect of a venous cuff at the venous anastomosis of PTFE graft AVFs in terms of stenosis development, hemodynamics and patency rates. METHODS: A subset of 40 patients from a multicenter study were enrolled into the study, of which 20 patients were randomized for venous cuff interposition. Duplex measurements to detect stenoses and volume flows were performed at 6, 12, 26 and 52 weeks postoperatively. Relative distension (RD) and wall shear rate (WSR) were calculated by means of vessel wall Doppler tracking (VWDT). RESULTS: The total number of stenoses was significantly less in the cuff group (21 vs. 33; p = 0.045). This feature was found at the site of the venous anastomosis (cuff 5; no cuff 12). Volume flow, graft and efferent vein diameters, RD and WSR in the graft and efferent vein were comparable for both groups. WSR in the venous anastomosis tended to be lower in the cuff group (768 vs. 1,448 s(-1), p = 0.068).Volume flows and WSR were significantly lower in failing grafts. Patency rates were similar in both groups (primary patency 13 vs. 29%; secondary patency 78 vs. 67%). CONCLUSIONS: A venous cuff at the venous anastomosis of PTFE graft AVFs results in less stenoses, but improved patency rates could not be demonstrated.     

Sarcoplasmic reticulum K(+) channels from human and sheep atrial cells display a specific electro-pharmacological profile

It has recently been proposed that the Ca(2+) uptake by the SR is inhibited by blocking Cl(-) and/or K(+) movements across this intracellular membrane. We have characterised the functional and pharmacological profile of the SR K(+) channel derived from human and sheep atrial cells. Mammalian atrial SR preparations were subjected to [(3)H]-ryanodine binding assays, SDS-PAGE analysis and channel protein reconstitution into planar lipid bilayers. Assessment of [(3)H]-ryanodine binding on the SR Ca(2+) release channel revealed that it was inhibited by both Ruthenium Red and Mg(2+) with IC(50) values of 4.11 microM and 9.12 m M, respectively. In crude populations as well as in all SR-enriched fractions, activity of K(+) selective channels was recorded. This channel displayed a high conductance value of 193 and 185 pS for human and sheep preparations respectively. Gating and conducting behaviours of this channel were unaffected by the addition of up to 5m M 4-Aminopyridine (4-AP), 100 n M Iberiotoxin (IbTX), 10 microM E-4031 and 30 microM amiodarone. However, 100n M Dendrotoxin (gamma-DTX) largely increase the occurrence of the SR K(+) channel subconducting states without an effect on the main unitary conductance. These results demonstrate that the SR K(+) channel, present in all mammalian atrial SR membranes tested (as assessed by [(3)H]-ryanodine binding and its typical inhibition by ruthenium red and the magnesium), displays different properties than those classically described for cardiac sarcolemmal K(+) channels. Despite the fact that the biophysical properties of the SR K(+) channel are well known, its molecular identity remains to be ascertained.     

Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results

Measurements of plasma normetanephrine and metanephrine provide a highly sensitive test for diagnosis of pheochromocytoma, but false-positive results remain a problem. We therefore assessed medication-associated false-positive results and use of supplementary tests, including plasma normetanephrine responses to clonidine, to distinguish true- from false-positive results. The study included 208 patients with pheochromocytoma and 648 patients in whom pheochromocytoma was excluded. Clonidine-suppression tests were carried out in 48 patients with and 49 patients without the tumor. Tricyclic antidepressants and phenoxybenzamine accounted for 41% of false-positive elevations of plasma normetanephrine and 44-45% those of plasma and urinary norepinephrine. High plasma normetanephrine to norepinephrine or metanephrine to epinephrine ratios were strongly predictive of pheochromocytoma. Lack of decrease and elevated plasma levels of norepinephrine or normetanephrine after clonidine also confirmed pheochromocytoma with high specificity. However, 16 of 48 patients with pheochromocytoma had normal levels or decreases of norepinephrine after clonidine. In contrast, plasma normetanephrine remained elevated in all but 2 patients, indicating more reliable diagnosis using normetanephrine than norepinephrine responses to clonidine. Thus, in patients with suspected pheochromocytoma and positive biochemical results, false-positive elevations due to medications should first be eliminated. Patterns of biochemical test results and responses of plasma normetanephrine to clonidine can then help distinguish true- from false-positive results.     

A "pheo" lurks: novel approaches for locating occult pheochromocytoma

Most, but not all, pheochromocytomas can be localized by computed tomography or magnetic resonance imaging. Here we introduce two novel approaches for localization of pheochromocytoma in a patient in whom conventional imaging modalities failed to show the tumor. First, we establish that measurements of plasma free metanephrines coupled with vena caval sampling are useful for localizing occult pheochromocytoma, particularly when elevations in plasma catecholamines are slight or intermittent. Second, we show that positron emission tomographic scanning using the imaging agent 6-[18F]fluorodopamine as a substrate for the norepinephrine transporter offers a highly effective method for tumor localization. These novel approaches may be of value in difficult cases, where biochemical and clinical evidence of pheochromocytoma is compelling, yet conventional imaging modalities fail to locate the tumor.     

Left internal mammary artery bypass dysfunction after revascularization of moderately narrowed coronary lesions. Colour-duplex ultrasound versus angiography study.

BACKGROUND: The left internal mammary artery (LIMA) is the conduit of choice for revascularization of coronary arteries and its popularity further increases in the era of mini-invasive coronary surgery. The aim of this study was first, to assess the accuracy of CDUS in predicting the LIMA graft dysfunction as compared to angiography, and secondly, to correlate the postoperative status of the LIMA graft with preoperative coronary artery stenosis severity of the bridged lesion. METHODS AND RESULTS: We examined 111 patients (pts) by colour-duplex ultrasound after myocardial revascularization by LIMA bypass (3.8 +/- 3.2 years after revascularization). LIMA was detected from the left supraclavicular approach at rest using the 7.5 MHz linear transducer. The ultrasound results were compared to contemporaneous angiography. The LIMA bypass patency was correlated with the preoperative coronary artery stenosis severity. The LIMA was detected by ultrasound in 92.8% (103) pts. At angiography, LIMA was patent and functional in 85 pts (76.6%, group A); in 25 subjects LIMA was stenosed or dysfunctional (22.5%, group B). In one patient the coronary subclavian steal syndrome was detected (0.9%). Haemodynamically moderate stenosis (50-60% by preoperative quantitative coronary angiography) was grafted in 5 pts of group A (6%), but in 10 pts of group B (40%) (P < 0.0001 vs group A). A peak systolic to peak diastolic velocity ratio (SDVR) of <2.0 yielded optimal accuracy to detect the absence of LIMA bypass dysfunction with a negative predictive value of 95%. CONCLUSION: 1. Revascularization of angiographically moderate coronary lesions is associated with a higher risk of postoperative graft dysfunction. 2. Colour-duplex ultrasound is a useful non-invasive tool for the postoperative follow-up of pts with a LIMA graft.     

Plasma N-terminal pro-B-type natriuretic peptide for prediction of death or nonfatal myocardial infarction following percutaneous coronary intervention

B-type natriuretic peptide (BNP) and the N-terminus of pro-BNP (NT-pro-BNP) have prognostic value in patients with heart failure and patients with acute coronary syndromes. Little is known about the prognostic value of baseline NT-pro-BNP alone or in combination with C-reactive protein (CRP) for clinical outcome after percutaneous coronary intervention (PCI). Within a single center registry of contemporaneous PCI, we investigated the prognostic value of baseline plasma NT-pro-BNP and CRP concentrations for the prediction of death or nonfatal myocardial infarction (MI) during 12 to 14 months of follow-up. Among 1,172 consecutive patients, the occurrence of death or MI increased significantly with baseline NT-pro-BNP before PCI (first quartile 0 of 294, second quartile 6 of 291 [2.1%], third quartile 4 of 294 [1.4%], fourth quartile 22 of 293 [7.5%)]; p <0.0001). NT-pro-BNP in the top quartile significantly predicted death (odds ratio [OR] 13.37, 95% confidence interval [CI] 4.50 to 40.38, p <0.0001) and was associated with nonfatal MI (OR 2.53, 95% CI 0.77 to 8.34, p = 0.22) An abnormal CRP was significantly associated with death (OR 3.47, 95% CI 1.26 to 9.54, p = 0.019). Stepwise multivariate logistic regression analysis identified age >65 years and NT-pro-BNP as independent significant predictors of death/MI (age OR 3.18, 95% CI 1.32 to 7.67, p = 0.01; NT-pro-BNP OR 4.57, 95% CI 2.07 to 10.10, p = 0.0001). Baseline NT-pro-BNP before PCI provides important, independent prognostic information for the occurrence of death or nonfatal MI during long-term follow-up.     

Abnormal ACTH-stimulation test in a patient with AIDS: adrenal insufficiency or toxoplasmosis?

We here report a 32-year old homosexual man with AIDS who had an abnormal ACTH stimulation test while taking megestrol actetate (megace). On further evaluation, he was found to have recurrent Non-Hodgkin lymphoma (spleen) and intracranial toxoplasmosis, perhaps imitating or aggravating symptoms suggestive of adrenal insufficiency (AI). We diagnosed secondary AI due to megace treatment and tapered this medication under simultaneous hydrocortisone replacement therapy. After the patient's intracranial toxoplasmosis had been treated with intravenous bactrim, his symptoms disappeared. We conclude that patients with AIDS on megace therapy should receive special attention in regards to the potential development of AI, especially in stress situations such as infections or pain.     

Comparison of Collateral Vascular Responses in the Donor and Recipient Coronary Artery During Transient Coronary Occlusion Assessed by Intracoronary Blood Flow Velocity Analysis in Patients

Objectives. This study was designed to evaluate the hemodynamic variables of the collateral circulation during acute coronary occlusion.

Background. There is limited information on the physiology of the collateral circulation in coronary artery disease.

Methods. Angiography of the contralateral donor artery was performed before and during balloon coronary occlusion in 57 patients with one-vessel disease. Recruitable collateral flow was assessed during coronary occlusion by blood flow analysis of the contralateral donor artery (n = 19) or the ipsilateral recipient artery (n = 15), or both (n = 23), using a Doppler catheter or guide wire. Ischemia was evaluated by the ST segment shift (≥0.1 mV) on a 12-lead electrocardiogram at 1 min of coronary occlusion.

Results. The presence (n = 39), compared with the absence (n = 18), of recruitable collateral vessels was associated with an increase of blood flow velocity in the donor artery (20 ± 19% vs. 4.8 ± 5.9% [mean ± SD], p = 0.003) and the recipient artery (velocity integral 7.2 ± 5.5 vs. 2.8 ± 2.2 cm, p = 0.02) related to a reduced relative collateral vascular resistance (9.2 ± 10 vs. 20 ± 11, p = 0.003). Collateral flow in the donor artery yielded a similar predictive value for recruitability of collateral vessels as collateral flow determined in the recipient artery or the coronary wedge/aortic pressure ratio (areas under the receiver operating characteristics curves 0.76 ± 0.07, 0.78 ± 0.08, 0.77 ± 0.07, respectively, p = NS). Collateral flow in the recipient artery was a better predictor for ischemia than collateral flow in the donor artery or angiographic grading of collateral vessels (areas 0.90 ± 0.05, 0.64 ± 0.10, 0.73 ± 0.07, respectively, p < 0.05).

Conclusions. Coronary blood flow velocity analysis of the donor and recipient coronary arteries can characterize the dynamics of the collateral circulation during acute coronary occlusion. The protective effect of recruitable collateral vessels relates to an increase of flow in the donor and recipient coronary arteries due to a reduced collateral vascular resistance. This study underscores the importance of physiologic variables for the evaluation of the function of recruitable collateral vessels.

(J Am Coll Cardiol 1997;29:1528–35)     

The role of androgens in sertoli cell proliferation and functional maturation: studies in mice with total or Sertoli cell-selective ablation of the androgen receptor

The role of androgens in the proliferation and maturation of Sertoli cells (SC) and the development of their capacity to support spermatogenesis remains poorly understood. We evaluated these functions in complete androgen receptor knockout (ARKO) and SC-selective androgen receptor knockout (SCARKO) mice. Compared with controls, ARKO mice exhibited a progressive reduction in SC number/testis, whereas SCARKOs showed minor changes, suggesting that androgen effects on SC number are not mediated via direct action on SCs. Immunoexpression of anti-Mullerian hormone (AMH), p27(kip1), GATA-1, and sulfated glycoprotein-2, which changes according to SC maturational status, occurred normally in ARKOs and SCARKOs. Functional capacity of SCs to support spermatogonia was similar in SCARKOs and controls, whereas ARKOs showed reduced capacity with age. SC capacity to support total germ cells revealed major deficits in ARKO and SCARKO adults, particularly with respect to postmeiotic germ cells. Using quantitative RT-PCR, the expression of SC markers was compared in d 50 testes. In ARKOs, expression of Pem, fatty acid binding protein, platelet-derived growth factor-A, and transferrin were all significantly reduced, whereas FSH receptor and AMH were increased. In SCARKOs, there were modest reductions in expression of cystatin-related gene highly expressed in testis and epididymis (cystatin-TE) and claudin-11, whereas expression of Pem, fatty acid binding protein, and platelet-derived growth factor-A was markedly reduced, highlighting these as potentially androgen-regulated SC genes that merit further study. In conclusion, androgen action is not required for maturation-dependent changes in immunoexpression of the SC markers AMH, p27(kip1), GATA-1, and sulfated glycoprotein-2 but is essential for expression of other SC genes, the attainment of normal SC number, and the support of meiotic and postmeiotic germ cell development.