The relation of interleukin-6, tumor necrosis factor-alpha, IL-2, and IL-2 receptor levels to cellular rejection, allograft dysfunction, and clinical events early after cardiac transplantation.

Immunoregulatory cytokines have been implicated in the pathophysiology of graft dysfunction after heart transplantation (HTx). In 15 consecutive patients undergoing HTx we prospectively determined levels of interleukin-6 (IL-6), tumor-necrosis-factor-alpha (TNF-alpha), interleukin-2 (IL-2), and soluble-interleukin-2-receptor (sIL-2-R) at eight points in time during biopsy and right heart catheterization and within 12 hr of echocardiography during the first three months after HTx. Blood was taken from the pulmonary arterial line. IL-6-levels correlated positively with hemodynamic and echocardiographic parameters of pump dysfunction--namely, pulmonary capillary wedge pressure, pulmonary arterial pressure, right atrial pressure, heart rate--and negatively with isovolumic relaxation time and stroke volume independent of the degree of cellular rejection as classified by the ISHLT criteria. A similar pattern was found for TNF-alpha- and sIL-2-R, while IL-2 correlated negatively with left and right heart filling pressures and positively with fractional shortening. In the three patients who died of sepsis or multiorgan failure within the study period IL-6-, TNF-alpha, and sIL-2-R-levels were elevated and IL-2-levels were suppressed compared with the 12 patients with a stable clinical course. IL-6 and sIL-2-R correlated positively while IL-6 and IL-2 correlated negatively. In this pilot study, a cytokine pattern with elevated levels of IL-6, TNF-alpha, and sIL-2-R as well as suppressed levels of IL-2 in the early period after HTx corresponds to impaired hemodynamics independent of cellular rejection and may indicate an unfavorable prognosis. These cytokines may therefore be useful for monitoring and warrant further study.

[In vitro validation of intravascular ultrasound, computerized and magnetic resonance tomography in diagnosis of atherosclerotic vascular segments in comparison with direct magnification radiography]. / In-vitro-Validisierung von intravaskulärem Ultraschall, Computer- und Magnetresonanztomographie zur Diagnostik atherosklerotischer Gefässsegmente im Vergleich zur direktradiographischen Vergrösserung.

The depiction of atherosclerotic vessel abnormalities is a prerequisite for percutaneous interventional therapy and long-term observations of peripheral artery disease. The aim of this in-vitro study was to determine the potentials and limitations of 12.5 and 20 MHz intravascular ultrasound, computed tomography and magnetic resonance (MR) imaging in comparison to direct magnification radiography for the localization and quantification of peripheral vessel wall calcifications. Forty-three postmortem, human iliac segments were examined by intravascular ultrasound (12.5 and 20 MHz), computed tomography and magnetic resonance tomography (gradient echo-and spin echo-technique). For comparative analysis, each segment was divided into eight sectors of 45 degrees each; using all five methods, the presence of calcified wall areas was examined in each sector, and luminal area (42 segments) and plaque area (32 isolated plaques) were quantitatively estimated. In the sonograms, the circumferential extension of the boundary between intima and media was measured. 122 of 344 sectors showed regional vessel wall calcifications. Sensitivity of 20 MHz intravascular ultrasound was 73% versus 59% with the 12.5 probe, specificity was 97% with 20 MHz, 96% with 12.5 MHz. Sensitivity of both 12.5 and 20 MHz intravascular ultrasound was higher with increased thickness of the calcified structures. 20 MHz ultrasound identified the intima-media boundary averaging 146.8 degrees of the vessel circumference; the corresponding value of 131.8 degree with 12.5 MHz did not differ significantly. Computed tomography detected calcifications with a sensitivity of 88%, specificity was 88%. With MR imaging, sensitivity of the gradient echo-technique was 94% versus a sensitivity of 86% with spin echo-technique. Quantification of luminal and plaque areas showed that luminal area was precisely estimated only by 20 MHz ultrasound (no significant difference to direct magnification radiography), whereas all other techniques showed significant overestimation. Plaque areas were markedly overestimated by computed tomography and MR imaging, too. In an in vitro set-up, intravascular ultrasound, MR tomography and computed tomography do not allow an authentic depiction of peripheral vessel wall architecture. Limited resolution, subintimal shadowing and and distortion are the main limitations of these new techniques so that details of regional vessel wall calcifications cannot be presented thoroughly. Relevant over-estimation of luminal and plaque areas must be considered.

Prognostic value of serum erythropoietin levels in late acute rejection of renal transplants.

Since renal allograft rejection is frequently associated with a blunted erythropoiesis, we investigated erythropoietin (EPO) serum concentrations in 17 patients with acute rejection, eight patients with chronic rejection, and 18 transplant recipients with stable graft function. All rejection episodes were proven by biopsy. Erythropoietin serum levels were significantly reduced in patients with chronic rejection (6.2 +/- 3.4 mU/mL; P < 0.01) compared with individuals with acute rejection (35.6 +/- 33.9 mU/mL) or stable graft function (24.0 +/- 19.7 mU/mL). Suppressed EPO levels were associated with marked anemia in chronic rejection patients. In a subgroup of patients with acute rejection and bad responses to an intensified immunosuppressive regimen or with transplant failure, we found significantly suppressed EPO levels (11.6 +/- 6.1 mU/mL) compared with a subgroup of patients with a beneficial acute rejection outcome (57.0 +/- 34.2 mU/mL; P < 0.01). A correlation between histologic parameters of acute rejection and hormone levels showed that signs of moderate glomerulitis were associated with elevated EPO levels, whereas lesions of moderate tubulitis were associated with low values. We conclude that serum EPO may have prognostic value for rejection outcome in renal transplant recipients.

Immunohistochemical distribution of chromogranins A and B and secretogranin II in neuroendocrine tumours of the gastrointestinal tract.

The aim of the present study was to investigate immunohistochemically the distribution of chromogranin A, chromogranin B, and secretogranin II in a series of 152 neuroendocrine tumours of the gastrointestinal tract. Tumour tissues from 25 argyrophil gastric carcinoids, 18 gastrin and 5 somatostatin-producing tumours, 4 'gangliocytic paragangliomas', 49 classical argentaffin and 2 L cell appendiceal carcinoids, 27 classical ileal carcinoids, 17 rectal carcinoids, and 5 poorly differentiated neuroendocrine tumours of the stomach and rectum were immunostained with antibodies against chromogranin A, chromogranin B, and secretogranin II. Chromogranin A was the major granin expressed in gastric carcinoids and in serotonin-producing carcinoids of the appendix and the ileum. In contrast, strong chromogranin B and secretogranin II immunoreactivity was found in rectal carcinoids, in which chromogranin A was rarely expressed. Since chromogranin A is a widely used marker for neuroendocrine differentiation, it is of diagnostic importance that some gastrin-producing tumours, 'gangliocytic paragangliomas', poorly differentiated neuroendocrine carcinomas, and appendiceal L cell carcinoids completely lacked chromogranin A positivity. It is concluded that the various neuroendocrine tumours of the gastrointestinal tract show distinctly different patterns of granin expression, probably reflecting their histogenetical origin.

Comparative analysis of glutaraldehyde-preserved porcine xenografts and fresh or glutaraldehyde-treated human aortic valves by holographic interferometry.

Although calcification and degeneration are recognized as the main causes of bioprosthetic heart valve failure, the reasons for such failure are not well understood. Hidden tissue anomalies in the valves may be the origin of later calcification. Application of hologram interferometry for non-destructive testing enables the detection of such tissue anomalies. A comparative study by holographic interferometry of ten porcine bioprosthetic valves (seven Carpentier-Edwards SAV, two BioImplant and one Valcor) with five human aortic valves before and after glutaraldehyde treatment is presented. Whereas irregularities were detected in the interferograms of eight out of ten bioprostheses, no similar distorted fringe pattern was found in the holographic interferograms of human specimens. The present results suggest that tissue abnormalities exist in standard bioprosthetic valves which are absent in human ones. These irregularities may be the origin of later calcification and valvular dysfunction.

[Glomus tumors: a diagnostic and surgical challenge?]. / Glomustumoren: eine diagnostische und chirurgische Herausforderung?

Within a population of 1150 vascular patients over a time period of 10 years we saw a carotid body tumor (synonymous chemodectoma) in only 11 cases. A correct preoperative diagnosis was found only in three patients. Before being treated by a specially trained team of vascular surgeons, eight patients had undergone inadequate operations. These were performed with a high incident of local complications. Simple bedside physical examination of the patient while looking for the signs of Fontaine and Kocher I + II (20) assures the diagnosis. Confirmation can be achieved by color-flow Doppler sonography (2). For the surgical resection, the only therapeutic alternative to the "gold standard" is angiography in digital subtraction technique which illustrates the blood supply of the tumor (70% exclusively by the external carotid artery). Also, it shows the typical intercarotid widening and the rich vascular conglomerate in between. Malignancy was detected in one case only (pulmonary metastasis). In two cases concomitant tumors of the jugular vein were seen. The interruption of the blood flow in the external carotid artery facilitates the surgical approach substantially. The ligature of this vessel (six patients) and the interposition of saphenous vein grafts (all 11 cases) for reconstruction of the internal carotid vessel were employed as the surgical strategy. Even the exstirpation of a large tumor (18 x 11 x 9 cm) extending from the skull base and almost reaching the left clavicular bone was successfully performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Successful long-term course after heart transplantation for anthracycline cardiomyopathy in a young boy despite neurological complications.

A now 14-year-old boy underwent orthotopic heart transplantation at the age of 13 for anthracycline cardiomyopathy which was a sequela of polychemotherapy for embryonal teratocarcinoma at the age of 1 year. Despite perioperative cerebellar infarction with signs of herniation which required emergency right cerebellar hemispherectomy the long-term course after 18 months turned out to be favorable with complete medical and psychosocial rehabilitation.

Validation of intravascular ultrasound in arteriosclerotic peripheral vessels.

In this in vitro-study, we validated intravascular ultrasound for the detection of irregular luminal contours, intraarterial structures, intimal thickening in peripheral arteriosclerotic human vessel segments and we compared sonographic criteria to the composition of arteriosclerotic lesions. Sixty-nine post-mortem segments of human peripheral arteries (6 patients) were fixed in formalin, examined with intravascular ultrasound and morphologically evaluated. Specificity, sensitivity, both positive and negative predictive value and accuracy of intravascular ultrasound for the detection of irregular luminal contours, intra-arterial structures and intimal thickening were determined for each of four quadrants. Ultrasonic features (echogeneity, homogeneity, shadowing of echoes) were also compared to the composition of lesions. Intravascular ultrasound detected regular (normal) luminal contours with a high specificity of 96.5%, a sensitivity of 65.0% and an accuracy of 88.4%. Intra-arterial structures were detected with a sensitivity of 88.6%, a specificity of 97.8% and an accuracy of 96.4%. Arteriosclerotic lesions could be localized with a sensitivity of 86.1%, a specificity of 99.1% and an accuracy of 86.9%. Intimal thickening was detectable with a sensitivity of 85.9%, a specificity of 87.8% and an accuracy of 86.2%. Meanwhile, fibrous, atheromatous and combined lesions without calcification did not show shadowing of echoes. The majority of fibrous or atheromatous lesions presented with homogeneous echoes showing hypo-, hyper- and normal density echoes. Using a 20-MHz transducer, homogeneity and echogeneity of echo patterns cannot accurately predict the different components of combined arteriosclerotic lesions.

Aortic valve replacement with cryopreserved pulmonary allograft.

Experimental as well as clinical data support the finding of using the pulmonary valve as a systemic semilunar valve. From January 1990 to December 1992, 89 patients received pulmonary cryopreserved allografts as aortic valve replacement. Sixteen subjects suffering from native or prosthetic valve endocarditis were included. Age ranged from 10 to 74 years. Sixty-five patients received isolated aortic valve replacement and 24 patients required additional surgical measures, such as coronary artery bypass graft, mitral valve reconstruction, replacement of the ascending aorta, supravalvular patch aortoplasty, ventricular septal defect closure, or myectomy. All operations were performed with normothermic bypass and cold cardioplegic arrest. Follow-up is maintained by visits to the outpatient clinic and echocardiographic assessment of the valve status every 3 months during the first year and every 6 months thereafter. There were four early and three late deaths. Four valves had to be removed: one intraoperatively and three 2, 4, and 24 months postoperatively. Echocardiographic assessment proved that gradients across the valve were low or absent. The majority of patients showed trivial or no aortic regurgitation during follow-up. No thromboembolic events have been observed and no new endocarditis occurred. Thus, event-free survival at 3 years is 87%. The results with pulmonary allografts have shown to be comparable to aortic allografts. Even in patients with acute native or prosthetic valve endocarditis, the use of cryopreserved pulmonary allografts has shown no adverse effects. We continue to implant cryopreserved pulmonary allografts in the aortic position. The long-term function of the valve, however, must be established, making continued evaluation of postoperative patients mandatory.

[Intravascular ultrasound in peripheral calcified vascular lesions: comparison with direct magnification radiography]. / Intravaskulärer Ultraschall bei peripheren verkalkten Gefässläsionen: Vergleich zur direktradiographischen Vergrösserung.

Intravascular ultrasound can detect calcified peripheral arteriosclerotic lesions by hyperdense echo patterns and shadowing of subintimal layers. Nevertheless, 20 MHz ultrasound systems have not been validated for the detection of peripheral calcifications; besides, it is unknown whether the depiction of calcified lesions by intravascular ultrasound depends on the morphology of the calcification. Histological evaluation of severely calcified arteries is difficult because the preparation of those specimens often causes artefacts, e.g., fracture of calcified structures. Direct magnification radiography, currently used in forensic medicine or skeleton examination, is based on a minimized focus and enables the edge-enhanced views of calcifications with high discrimination. In this in-vitro-study direct radiological magnification was used to validate intravascular ultrasound. Forty-nine segments of human peripheral arteries were fixed in formalin, examined with intravascular ultrasound and, as a reference, radiographically magnified using a newly developed microfocus x-ray tube. Sensitivity, specificity, positive and negative predictive value, and accuracy of intravascular ultrasound for the detection of calcified wall areas were determined and compared to the appearance (configuration, circumferential and areal expansion, density, number of fragments) of these calcifications. Thicknesses of 110 single calcified structures were estimated on sonograms and radiograms. The overall sensitivity of the 20 MHz intravascular ultrasound system for the detection of calcification in 913 sectors was 70%, specificity 53%, positive predictive value 66%, negative value 58% and accuracy 62%. The depiction of calcified regions by direct magnification radiography showed that the sensitivity strongly depended on the density of the calcification. Sensitivity was 81% with calcified lesions of high density, but only 51% with lesions of low density.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromogranin A, secretogranin II and vasoactive intestinal peptide in phaeochromocytomas and ganglioneuromas.

By means of immunohistochemistry we analysed the distribution of chromogranin A, secretogranin II and vasoactive intestinal peptide (VIP) in 16 phaeochromocytomas, two cases of combined phaeochromocytoma-ganglioneuroma and four adrenal ganglioneuromas. Chromogranin A was found in the majority of phaeochromocytes and in mixed phaeochromocytomas-ganglioneuromas. Secretogranin II was present to a lesser degree in phaeochromocytes, but strong immunostaining was found in most ganglion cells of phaeochromocytomas, in the ganglioneuroma component of combined tumours and in adrenal ganglioneuromas. Vasoactive intestinal peptide was present in some ganglion cells of phaeochromocytomas, in the ganglioneuroma component of mixed tumours and in three of four adrenal ganglioneuromas. On semi-adjacent sections a co-localization of VIP and secretogranin II was demonstrated. These results indicate that neuronal differentiation is accompanied by an increased immunohistochemical expression of secretogranin II. Therefore, secretogranin II may be a useful marker for ganglion cell differentiation.

Echinococcal cyst of the interventricular septum: a rare cause of myocardial ischemia.

A 30-year-old woman developed ischemia-like chest pain due to myocardial compression by an intracardiac cyst. The cyst was located in the interventricular septum. Its etiology could not be ascertained despite several diagnostic measures but exstirpation was indicated by the clinical symptoms. Intraoperatively the diagnosis of echinococcosis was established. The cyst was extirpated in toto without perforation of the thinned interventricular septum. Postoperatively the patient was symptomfree.

[Diagnostic validity of imaging methods in the detection and observation of the progress of cases of invasive aspergillosis of the blood vessels of the lung]. / Diagnostische Validität bildgebender Verfahren bei Detektion und Verlaufsbeobachtung des gefässintensiven Aspergillus-Befalls der Lunge.

Chest radiographs and thoracic computed tomograms (CT) of 21 patients with oncologic disease and vasoinvasive pulmonary aspergillosis (PA) were assessed and compared. CT findings were interpreted by comparison with histologic lung specimens of 28 lethal cases of PA. The analysis showed that in the early stages of infection findings suggestive of PA were only found in 29% of cases (n = 6) on conventional radiographs, whilst CT suggested the presence of PA in all cases (n = 21). In advanced stages, conventional radiographs suggested the presence of PA in 38% of cases (n = 8), which was not significantly different from that value for early disease. The comparison of CT with histopathologic findings allows their objective interpretation; such studies provide an improvement in both detection rate and characterization of CT changes in PA.

Hepatosplenic candidosis--a late manifestation of Candida septicemia.

Hepatolienal candidosis was diagnosed in 27 patients suffering from malignant hematologic disorders. All patients had received intensive cytostatic chemotherapy and developed septic, antibiotic-resistant temperatures during severe treatment-induced neutropenia. During neutropenia hepatic and splenic foci were not identified by imaging procedures. Foci were poorly defined histologically. Blastospores and pseudomycelia were seen in non-reactive tissue and within necrotic areas in the liver, spleen, and other organs. Only Candida species could be isolated. One to four weeks after granulocyte recovery, round liver and splenic foci were demonstrated by sonographic and CT scans. Histologically, there were necrotic areas with blastospores and pseudohyphae exhibiting different degrees of cellular border reaction. Whereas the maximum diameter of fungal foci in aplasia was 0.4 cm, these increased in size to 1.5 cm after granulocyte regeneration.