[Dermatological side effects during therapy with serotonin noradrenaline reuptake inhibitors]. / Dermatologische Nebenwirkungen unter Therapie mit Serotonin-Noradrenalin-Wiederaufnahmehemmern.

Bleeding complications during therapy with serotonin norepinephrine reuptake inhibitors are a well-known phenomenon. We report a patient who developed ecchymosis during administration of duloxetine. As a correlate we detected a transient platelet dysfunction. After converting to venlafaxine therapy, another antidepressant with a dual mechanism of action, the patient showed normal platelet function. We finally achieved remission of the episode.

Commentary: Shoot the renals!

Atherosclerotic renal artery stenosis (ARAS) is a growing dilemma. The condition is increasingly common and can promulgate hypertension and result in renal failure. However, patients with ARAS generally die owing to their coronaries or cerebral vessels. Intervention, by stenting or angioplasty is beloved and believed, but not proved. The American Heart Association has recently published guidelines regarding patients at high risk for ARAS who are potential candidates for revascularisation. Since this phraseology includes practically every patient with atherosclerosis, these guidelines appear ill advised.

Preparation of protected peptidyl thioester intermediates for native chemical ligation by Nalpha-9-fluorenylmethoxycarbonyl (Fmoc) chemistry: considerations of side-chain and backbone anchoring strategies, and compatible protection for N-terminal cysteine.

Native chemical ligation has proven to be a powerful method for the synthesis of small proteins and the semisynthesis of larger ones. The essential synthetic intermediates, which are C-terminal peptide thioesters, cannot survive the repetitive piperidine deprotection steps of N(alpha)-9-fluorenylmethoxycarbonyl (Fmoc) chemistry. Therefore, peptide scientists who prefer to not use N(alpha)-t-butyloxycarbonyl (Boc) chemistry need to adopt more esoteric strategies and tactics in order to integrate ligation approaches with Fmoc chemistry. In the present work, side-chain and backbone anchoring strategies have been used to prepare the required suitably (partially) protected and/or activated peptide intermediates spanning the length of bovine pancreatic trypsin inhibitor (BPTI). Three separate strategies for managing the critical N-terminal cysteine residue have been developed: (i) incorporation of N(alpha)-9-fluorenylmethoxycarbonyl-S-(N-methyl-N-phenylcarbamoyl)sulfenylcysteine [Fmoc-Cys(Snm)-OH], allowing creation of an otherwise fully protected resin-bound intermediate with N-terminal free Cys; (ii) incorporation of N(alpha)-9-fluorenylmethoxycarbonyl-S-triphenylmethylcysteine [Fmoc-Cys(Trt)-OH], generating a stable Fmoc-Cys(H)-peptide upon acidolytic cleavage; and (iii) incorporation of N(alpha)-t-butyloxycarbonyl-S-fluorenylmethylcysteine [Boc-Cys(Fm)-OH], generating a stable H-Cys(Fm)-peptide upon cleavage. In separate stages of these strategies, thioesters are established at the C-termini by selective deprotection and coupling steps carried out while peptides remain bound to the supports. Pilot native chemical ligations were pursued directly on-resin, as well as in solution after cleavage/purification.

Determination of renal arterial stenosis severity: comparison of pressure gradient and vessel diameter.

PURPOSE: To determine the hemodynamic significance of arteriographically detected renal arterial stenosis by obtaining pressure gradients with a miniaturized pressure guide wire. MATERIALS AND METHODS: Forty-six renal arterial stenoses in 38 patients were assessed in terms of severity and then subjected to gradient determination before and after angioplasty. The patients (mean age, 63 years) had a mean serum creatinine value of 1.3 mg/dL +/- 0.4 (114.9 micromol/L +/- 35.4 [SD]) and required on average three medications for blood pressure control. The mean degree of stenosis diameter was 51% +/- 17 (range, 12%-85%). RESULTS: The systolic and mean arterial pressure gradients with and those without vasodilatation were highly correlated with stenosis severity, systolic blood pressure, and serum creatinine as a curvilinear fit (r = 0.9, P <.01). At 50% stenosis severity, the mean pressure gradient was 22 mm Hg. CONCLUSION: Patients with a pressure gradient greater than 20 mm Hg should be good candidates for renal arterial dilatation, and use of the pressure guide wire will facilitate interventional decisions.

An Internet-based simulation model for nitrogen management in agricultural settings.

Complex chemical, physical, and biological processes mediate nitrogen (N) transformations and movement during agricultural production, making the optimization of fertilizer use and environmental protection exceedingly difficult. Various computer models have been developed to simulate the site-specific fate and transport of N resulting from different crop production scenarios, but these models are very complex and difficult to use for most farmers, consultants, and conservationists. In an effort to facilitate access and simplify the use of sophisticated models, the U.S. Department of Agriculture (USDA) has developed an Internet-based nitrogen analysis tool. Based on the Nitrate Leaching and Economic Analysis Package (NLEAP), the Web site allows a user to conduct multiyear N simulation modeling specific to a crop field. Servers handle much of the required data assembly and formatting, thus sparing the user"s resources. Model runs are executed on the servers and the results are transmitted to the user. This new tool is presented along with early implementation results.

[Renovascular illness: prevalence and therapy in patients with coronary heart disease]. / Die renovaskuläre Erkrankung: Prävalenz und Therapie bei Patienten mit koronarer Herzerkrankung.

To explore the relationship between coronary artery disease and renal vascular disease, we performed renal arterial angiography in 609 patients undergoing coronary angiography for suspected coronary artery disease. We defined renal artery stenosis as nonsignificant (< 40%), borderline (40-60%) and significant (> 60%). One-hundred fifty-two patients had renal artery stenosis, while 457 did not. Two-hundred and ten patients had no coronary disease; of these, only 9 had renal artery stenosis. On the other hand, the 143 patients with renal artery stenosis, when subdivided, had similar degrees of coronary disease; three vessel disease was significantly more common than one or two vessel disease in all groups. Renal artery stenosis of all severity degrees was associated with common atherosclerotic risk factors. However, hypertension was not a clue to the presence of renal artery stenosis. To evaluate the effect of percutaneous revascularization on hypertension and renal function all 51 patients with significant renal artery stenosis were treated by primary stent implantation and were followed up for 6 months. Stent implantation showed a marked decrease in systolic and diastolic blood pressure (163 +/- 30 to 145 +/- 17 and 93 +/- 18 to 83 +/- 10 mmHg; p = 0.008) with a decrease in the amount of antihypertensive medication but without beneficial effect on serum creatinine during follow-up (1.46 +/- 0.70 mg/dl to 1.39 +/- 0.58 mg/dl, p = ns). We conclude that renal artery stenosis of any severity is strongly suggestive of three vessel coronary artery disease. The fact that renal stenting lowers blood pressure decreases antihypertensive drugs and increases medication flexibility in patients with coronary artery disease would support the notion of revascularization in patients with significant stenoses.

Clinical and angiographic outcome in patients with in-stent restenosis and repeat target lesion revascularisation in small coronary arteries.

OBJECTIVE: To evaluate the clinical and angiographic outcome in patients with in-stent restenosis in small coronary arteries and repeat target lesion revascularisation. DESIGN: Patients with in-stent restenosis in coronary arteries < or = 2.85 mm were eligible for the study and underwent target lesion revascularisation. Clinical and angiographic variables were assessed during a six month follow up period. RESULTS: 73 patients with 79 lesions were treated by percutaneous transluminal coronary angioplasty (47%), excimer laser angioplasty (25%), or restenting (28%). The mean (SD) reference diameter before target lesion revascularisation was 2.12 (0.5) mm. Procedural success was achieved in all cases, but 57% of the patients had restenosis after six months. The rate of further restenosis was higher with laser angioplasty (78%) than with restenting (47%) or balloon angioplasty alone (49%, p < 0.05). CONCLUSIONS: Treatment for in-stent restenosis in small coronary arteries is feasible and safe, with a second restenosis rate comparable to large coronary artery series. The strategy of target lesion revascularisation influences further in-stent restenosis, with an increased rate with laser angioplasty compared with restenting and repeat dilatation alone.

Postcatheterization pseudoaneurysms and arteriovenous fistulas: repair with percutaneous implantation of endovascular covered stents.

PURPOSE: To assess the effectiveness and safety of endovascular covered stents in the management of pseudoaneurysms and arteriovenous fistulas after cardiac and vascular catheterization. MATERIALS AND METHODS: Twenty-six endovascular covered stents were used to repair 16 pseudoaneurysms, nine arteriovenous fistulas, and one combined lesion after femoral arterial puncture for diagnostic coronary angiography and/or angioplasty. Fistulas and aneurysms were in the superficial femoral artery in 16 cases, in the deep femoral artery in six cases, and in the common femoral artery in four cases. Implantation was performed from the opposite femoral artery in most cases. It was not possible to treat three additional cases transcutaneously for technical reasons (three of 29 cases). RESULTS: Percutaneous closure of the lesions with an endovascular covered stent was successful in 26 of 29 cases. Initial follow-up showed good stent patency. Two major complications were observed after stent implantation. During follow-up (about 1 year in 23 of 26 patients [88%]), stent thromboses were detected in four of 23 patients (17%) with follow-up color duplex flow imaging. CONCLUSION: Implantation of endovascular covered stents is an effective and safe method for the percutaneous closure of pseudoaneurysms and arteriovenous fistulas. Thus, endoluminal vascular repair with covered stents offers an alternative therapeutic approach to vascular surgery in selected patients.

Percutaneous treatment of pseudoaneurysms and arteriovenous fistulas after invasive vascular procedures.

Development of femoral artery pseudoaneurysms and arteriovenous fistulas represents a continuing problem after vascular diagnostic and interventional procedures. For most patients, ultrasound-guided compression is an effective method of treating such complications. However, in patients requiring a continuous anticoagulant regimen, in those with large arteriovenous fistulas or in patients suffering from painful groin hematomas, compression repair is less successful. We therefore assessed the feasibility, efficacy, and long-term results of interventional percutaneous treatment of these complications. In a 40-month period, we treated 53 consecutive patients with 30 pseudoaneurysms, 21 arteriovenous fistulas, and 2 combined lesions. The intervention was successful in 47 patients: 32 lesions were treated by implantation of covered stents, 14 by embolization techniques, and 1 by a combined procedure, surgical repair being necessary only in 6 patients. After a clinical and ultrasonic follow-up of 301 +/- 280 days, we noticed four late stent occlusions, especially in patients with poor peripheral runoff. Lesions with a distinct connection channel to the vessel lumen should be treated by coil embolization. In lesions originating from the femoral bifurcation with a broad base, surgical repair is necessary. Stenting of the superficial femoral artery with poor runoff should be avoided. Our results suggests that percutaneous closure of false aneurysms and arteriovenous fistulas after invasive procedures with unsuccessful ultrasonic compression repair is an attractive alternative to surgical treatment.

A novel isoform of the smooth muscle cell differentiation marker smoothelin.

Studies on smooth muscle cell differentiation and those on vascular development in mouse and humans have long been hampered by the lack of suitable markers. Here we describe a novel, large isoform of smoothelin, a structural protein of differentiated, contractile smooth muscle cells. The protein, which is highly conserved in mouse and humans, shows homology with other cytoskeleton-associated smooth muscle cell proteins and contains an actinin-type actin-binding domain. Northern blot analysis from various mouse organs identified short and long smoothelin mRNA forms, which exhibit distinct tissue expression patterns. The short form is highly expressed in visceral muscle tissues such as intestine and stomach and is not detectable in brain, while the long mRNA form is expressed in all vascularized organs. These results may provide new tools and approaches to study both smooth muscle cell differentiation and proliferative vascular disease.

Treatment of carotid artery stenosis by elective stent placement instead of carotid endarterectomy in patients with severe coronary artery disease.

Patients with concomitant cardiac and cerebrovascular disease undergoing revascularization procedures are at high risk of both, cardiac and cerebrovascular complications. The purpose of our study was to evaluate the feasibility of prior elective carotid artery stenting as an alternative treatment procedure to carotid endarterectomy (CEA) in patients with concomitant coronary artery disease (CAD), who clearly needed coronary revascularization. We offered extracranial internal carotid stenting to 85 patients with 89 significant carotid stenoses. Out of these, 19 patients were symptomatic. The quantitative mean reduction in diameter was 77 +/- 11%. Stent implantation was successful in 88 lesions. Two disabling major and 3 reversible minor strokes occurred periprocedurally. Three patients showed asymptomatic restenosis and stent deformation was detected in 2 patients. Based on this experience, carotid stenting in high risk patients with severe coronary artery disease is feasible and safe and might be indicated as an alternative procedure for combined surgery.

Elective stenting of carotid artery stenosis in patients with severe coronary artery disease.

AIMS: To evaluate the feasibility and safety of elective carotid stent implantation in patients with carotid stenoses and concomitant coronary artery disease, as an alternative to combined carotid and coronary surgery. METHODS: We treated 50 patients with >70%, stenoses in 53 carotid arteries with balloon angioplasty followed by elective stent implantation. All patients had severe coronary artery disease, and/or mitral insufficiency, aortic stenosis, rhythm disorders or generalized arteriosclerosis. In three patients the opposite carotid artery was occluded; nine patients had bilateral stenoses of which two received stents bilaterally. RESULTS: Fifty-six successful stent implantations (42 Wallstents, eight BeStents, two AVE-Microstents, one Palmaz Schatz stent, three Sito stents) were performed, reducing the baseline percent stenosis from 78 +/- 18%, to 13 +/- 11%. Complications included three transient ischaemic attacks, one minor and one major stroke. Follow-up was available for 46 patients over a mean of 10 months. Three asymptomatic restenoses and one deformation of a BeStent occurred. CONCLUSION: Our preliminary results indicate that carotid artery stenting in patients with concomitant severe coronary artery disease is feasible, safe, and may be an alternative to combined carotid and coronary surgery.

Ostial renal artery stent placement for atherosclerotic renal artery stenosis in patients with coronary artery disease.

To test the utility of endoprosthetic treatment for ostial renal artery stenosis, and to examine blood pressure and its treatment, serum creatinine, and restenosis rate, 44 ostial renal stent placements were performed in 30 patients with concomitant coronary artery disease, arterial hypertension, and the indication for angiotensin converting enzyme (ACE) therapy. There was a marked decrease in systolic and diastolic blood pressure (163+/-30 to 145+/-17 and 93+/-18 to 83+/-10 mm Hg; P < 0.008) with a decrease in number of medication (3.2+/-0.9 to 2.8+/-1.0; P = 0.005). In 5 out of 8 patients not receiving an ACE inhibitor, this drug could be added. Serum creatinine changed from 1.46+/-0.7 mg/dl to 1.39+/-0.58 mg/dl (P = ns). Three patients showed restenosis (12.5%). Ostial stenting lowers blood pressure, decreases antihypertensive drugs and increases medication flexibility.

Relation between arteriosclerosis in the coronary and renal arteries.

This study analyzes the severity of coronary artery disease in terms of the severity of renal artery disease in 609 patients undergoing coronary and renal angiography. The presence of renal artery disease of any severity is strongly suggestive of advanced coronary artery disease.

Stent implantation in patients with superior vena cava syndrome.

OBJECTIVE: The purpose of this study was to determine the feasibility of using Wallstent implantation to treat superior vena cava syndrome due to malignant tumors. SUBJECTS AND METHODS: Digital subtraction angiography showed obstruction of the superior vena cava in 13 patients who then underwent transluminal dilatation and Wallstent implantation. The patients were treated with IV heparin and monitored in the emergency department. Thereafter, they were treated with a platelet inhibitor for 4 weeks. RESULTS: Because their signs and symptoms improved, patients were able to resume radiation therapy, chemotherapy, or both. One patient died of cardiac arrhythmia 1 day after stent placement. Although eight patients have subsequently died of their bronchial or thyroid gland tumors, superior vena cava syndrome did not recur in any patient. CONCLUSION: Percutaneous implantation of Wallstent endoprostheses provides excellent palliation for superior vena cava syndrome.

Evaluation of an intelligent seat system.

This study was conducted to evaluate the effect of an intelligent seat system, a microprocessor-based interactive seat that automatically adjusts itself to fit a seated individual by making pressure-sensitive adjustments on its own. First, a standard American automobile seat ('baseline' seat) was assessed for comfort. Subjective ratings of comfort, pressure distribution and seated anthropometric measurements were recorded for 20 test subjects. These measurements were recorded while the subjects maintained a simulated driving position in a seat buck. The comfort scale was based on a rating of 1 to 10, with 1 corresponding to 'very poor' and 10 corresponding to 'very good.' Based on a nonlinear, multiple regression model that had been previously developed, the comfort rating of the seat was predicted based on the subjective ratings and the recorded values of 450 pressure measurements from 20 subjects. The predicted comfort value was 7.46 for the baseline seat. Following the baseline assessment, the intelligent seat system was installed into the standard American automobile seat. The objective and subjective assessments were then repeated for 17 subjects and the new predicted comfort rating was 8.06. A t-test performed on the subjective and objective measures indicated that this was a significant improvement in seat comfort. Overall, subjects felt the self-adjusting seat was more customized and more comfortable, providing a better fit.

Echocardiographic manifestations of mediastinal masses compressing or encroaching on the heart.

Because of its central position within the thorax, the heart can be encroached upon by masses originating in either anterior, posterior, or superior mediastinum. A distinction may be made between (A) Encroachment: distortion or partial displacement of one or more cardiac chambers by a contiguous mediastinal mass, without adverse hemodynamic effects, and (B) Compression: resulting in clinical manifestations similar to tamponade. Transthoracic and, recently, transesophageal echocardiography have been found useful in detecting mediastinal masses, the information obtained being complementary or preliminary to more complete imaging by CT or MRI. Anterior masses tend to compress the right heart chambers; posterior masses impinge on or compress the left atrium or ventricle, particularly the former. The wide variety of echographic appearances are briefly reviewed. Recently TEE has made it possible to diagnose masses obstructing the superior vena cava or pulmonary veins. A common, though little known, type of posterior mediastinal encroachment that echocardiographers need to be aware of is that of abnormal esophageal/gastric masses including hiatus hernia and esophageal carcinoma, which have typical two-dimensional echo features and may sometimes simulate left atrial masses.

Assessment of echocardiographic left ventricular mass before and after acute volume depletion.

Left ventricular mass calculations are often performed to assess the need or effectiveness of antihypertensive drug therapy. However, there are multiple potential errors that may affect the accuracy of these calculations, which can possibly include acute changes in preload. Therefore, to assess the hypothesis that acute volume depletion might alter calculated left ventricular mass, 15 normotensive healthy male volunteers underwent standard M-mode echocardiographic evaluations (at the level of the chordae tendineae guided by two-dimensional echocardiography) before and 2 h after 40 mg of intravenous furosemide. One patient was eliminated due to hypotension prior to the final echocardiogram. The echocardiograms were blinded to patient identity and the time sequence and read separately by two investigators. Four to five cycles were read per echocardiogram by each investigator. All values measured were the mean of the two investigators. Echocardiographic measurements were derived by both the American Society of Echocardiography and Penn conventions. An average urine volume of 1728 mL was collected, and the mean weight change 2 h after furosemide administration was 1.78 kg (P = .001). Penn left ventricular diastolic diameter (1.8 mm, P = .015) and left ventricular mass index (10 g/m2, P = .04) were significantly decreased; however, there was no significant change in septal, posterior, or relative wall thicknesses. As it is unreasonable to believe that acute remodeling of the left ventricle resulted in a decline in left ventricular mass in 2 hours, it is concluded that acute volume changes resulted in a decrease in left ventricular mass measurement due to the influence of diastolic diameter on the calculation of cardiac mass.