[Periodic fever and pancytopenia in a 35-year-old patient]. / Periodisches Fieber und Panzytopenie bei einem 35­jährigen Patienten.

MEDICAL HISTORY AND INITIAL PRESENTATION: A 35-year-old patient with a previous history of persistent episodic fever, sore throat, myalgia, and cephalgia presented for evaluation of pancytopenia. He had no recent travel history, except for a stay in Italy 1 year prior to admission and in Spain several years in the past. DIAGNOSTIC WORKUP: Laboratory evaluation confirmed pancytopenia, agranulocytosis, and elevated infection parameters without indicative serological results en par with lymphadenitis colli. Computed tomography scanning revealed cervical lymphadenopathy, hepatosplenomegaly, and colitis with occult perforation of the sigmoid colon. Bone marrow biopsy showed an infiltration of polyclonal plasma cells. Lymph node biopsy was compatible with necrotizing lymphadenitis. DIAGNOSIS: Polymerase chain reaction analysis of a lymph node specimen confirmed the presence of Leishmania species, thereby enabling the diagnosis of visceral Leishmania. THERAPY COURSE: Treatment with liposomal amphotericin B was initiated. Both fever and lymphadenopathy quickly resolved. CONCLUSION: VL is a clinically pleiotropic, severe disease with fatal outcome if left untreated. It often presents with distinct similarities to hematologic malignancies. Exacerbation can occasionally occur as fulminant macrophage activation syndrome. Disease incidence is globally increasing and has not peaked as yet. A complex interplay between pathogen and the immune system is the key pathophysiological mechanism.

[Percutaneous Phil™-Embolization for Preoperative Therapy of Carotid Body Paragangliomas]. / Perkutane Phil™-Embolisation zur präoperativen Therapie von Karotis-Paragangliomen.

Introduction: Paragangliomas are rare tumors representing a therapeutic challenge. In particular, the surgical removal may lead to life-threatening bleeding. The preoperative percutaneous embolization is an alternative that allows a high closure rate of tumor-feeding vessels in a short intervention time and thus significantly reduces intraoperative bleeding probability. Complete tumor resection is facilitated thereby. The use of a new non-adhesive liquid embolic agent is presented here. Methods: A 50-year old patient presented with 4 cm large paraganglioma of the carotid body (Shamblin II). A percutaneous embolization with 7 ml PHIL™ (injectable precipitating hydrophobic liquid) was performed preoperatively. 24 h later the complete surgical resection of the tumor was performed. Results: A good distribution of the liquid embolic agent could be achieved over the entire tumor. Intraoperative resection of the tumor was much easier and faster due to low bleeding tendency over the entire surface of the tumor. Total blood loss was less than 50 ml. All adjacent nerve and arterial structures could be spared. Postoperative nerve function was normal and the patient was discharged on the 4th postoperative day. Conclusion: The combination of percutaneous embolization and surgical resection provides a safe combination in the treatment of advanced carotid body paragangliomas. The use of a novel liquid embolic agent may possibly further optimize the therapy.

[Case report of granulomatous necrotizing sialadenitis. Rarity of first manifestation in submandibular gland]. / Fallbericht einer granulomatös-nekrotisierenden Sialadenitis. Rarität einer Erstmanifestation in der Glandula submandibularis.

This article presents the case of a 43-year-old male patient with recurrent painful swelling of the right submandibular gland. Submandibulectomy was performed. Histological investigations showed an intense granulomatous inflammation with severe destruction of the parenchyma. The inflammatory infiltrate consisted of abscesses with neutrophilic and eosinophilic granulocytes and ill-defined granulomas with multinucleated giant cells. Some of the blood vessels showed evidence of vasculitis. After further clinical and serological investigations with highly elevated levels of cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) and antiproteinase-3 antibodies, a rare limited disease of granulomatous polyangiitis (Wegener granulomatosis) was finally diagnosed. Such a manifestation of the disease is exceedingly rare; therefore, only single case reports have so far been described. The certain establishment of the diagnosis seems to be challenging because of the lack of involvement of the respiratory tract and the kidneys. In this case a histological assessment and clinical findings are mandatory for the correct diagnosis.

Prognostic significance of histologically detected lymph node micrometastases of sizes between 0.2 and 2 mm in colorectal cancer.

PURPOSE: Minimal lymph node involvement is a potential prognostic factor in colorectal cancer. The International Union Against Cancer defined tumour deposits between 0.2 and 2 mm as micrometastases and clusters and single-cell infiltrations below this cutoff as isolated tumour cells. Nevertheless, only a minority of studies discriminated metastatic involvements according to this definition. METHODS: In order to investigate the prognostic significance of micrometastases (0.2-2 mm), we performed a retrospective study enrolling 44 routinely diagnosed micrometastatic cases within 15 years which represent about 1% of our cases. These cases have been re-evaluated. RESULTS: Seven of the micrometastatic cases turned out to be macrometastases after step sectioning. Complete follow-up was available in 33 remaining cases. Collections of node-negative and macrometastatic cases served as control groups. The Kaplan-Meier curves of macro- and micrometastatic cases showed a similar adverse course (p = 0.830) especially during the first 40 months. The 5-year-survival rates were 51, 60 and 64 months for macro-, micrometastatic and node-negative cases, respectively. The difference in overall survival, however, reached only a statistical trend and was not significant (p = 0.137). After re-evaluation with step sections and cytokeratin immunohistochemistry out of an initial 91 node-negative cases, 11 (12%) cases were identified with isolated tumour cells and one (1%) case with a micrometastasis. CONCLUSIONS: Our data show that micro- and macrometastatic colorectal cancers show very similar survival rates. Therefore, efforts to improve the detection of lymph node micrometastases seem to be justified.

Neuropeptide Y cotransmission with norepinephrine in the sympathetic nerve-macrophage interplay.

The CNS modulates immune cells by direct synaptic-like contacts in the brain and at peripheral sites, such as lymphoid organs. To study the nerve-macrophage communication, a superfusion method was used to investigate cotransmission of neuropeptide Y (NPY) with norepinephrine (NE), with interleukin (IL)-6 secretion used as the macrophage read-out parameter. Spleen tissue slices spontaneously released NE, NPY, and IL-6 leading to a superfusate concentration at 3-4 h of 1 nM:, 10 pM:, and 120 pg/ml, respectively. Under these conditions, NPY dose-dependently inhibited IL-6 secretion with a maximum effect at 10(-10) M: (p = 0.012) and 10(-9) M: (p < 0.001). Simultaneous addition of NPY at 10(-9) M: and the alpha-2-adrenergic agonist p-aminoclonidine further inhibited IL-6 secretion (p < 0.05). However, simultaneous administration of NPY at 10(-9) M: and the beta-adrenergic agonist isoproterenol at 10(-6) M: or NE at 10(-6) M: significantly increased IL-6 secretion (p < 0.005). To objectify these differential effects of NPY, electrical field stimulation of spleen slices was applied to release endogenous NPY and NE. Electrical field stimulation markedly reduced IL-6 secretion, which was attenuated by the NPY Y1 receptor antagonist BIBP 3226 (10(-7) M, p = 0.039; 10(-8) M, p = 0.035). This indicates that NPY increases the inhibitory effect of endogenous NE, which is mediated at low NE concentrations via alpha-adrenoceptors. Blockade of alpha-adrenoceptors attenuated electrically induced inhibition of IL-6 secretion (p < 0.001), which was dose-dependently abrogated by BIBP 3226. This indicates that under blockade of alpha-adrenoceptors endogenous NPY supports the stimulating effect of endogenous NE via beta-adrenoceptors. These experiments demonstrate the ambiguity of NPY, which functions as a cotransmitter of NE in the nerve-macrophage interplay.

A tissue-like culture system using microstructures: influence of extracellular matrix material on cell adhesion and aggregation.

Special microenvironmental conditions are required to induce and/or maintain specific qualities of differentiated cells. An important parameter is the three-dimensional tissue architecture that cannot be reproduced in conventional monolayer systems. Advanced tissue culture systems will meet many of these demands, but may reach their limits, especially when gradients of specific substances over distinct tissue layers must be established for long-term culture. These limitations may be overcome by incorporating microstructures into tissue-like culture systems. The microstructured cell support presented consists of a flat array of 625 cubic microcontainers with porous bottoms, in which cells can be supplied with specific media from both sides of the tissue layer. Permanent cell lines and primary rat hepatocytes have been used to test the culture system. In order to define reproducible conditions for tissue formation and for cell adherence to the structure, several ECM (extracellular matrix) components were tested for coating of microstructured substrata. The described tissue culture system offers great flexibility in adapting the cell support to specific needs.

Microsystems in medicine.

The complexity of modern surgical and analytical methods requires the miniaturisation of many medical devices. The LIGA technique and also mechanical microengineering are well known for the batch fabrication of microsystems. Actuators and sensors are developed based on these techniques. The hydraulic actuation principle is advantageous for medical applications since the energy may be supplied by pressurised balanced salt solution. Some examples are turbines, pumps and valves. In addition, optical sensors and components are useful for analysis and inspection as represented by microspectrometers and spherical lenses. Finally, plastic containers with microporous bottoms allow a 3-dimensional growth of cell culture systems.

29Si CP/MAS NMR of phosphorus-bearing organosilicon compounds.

While liquid-state 29Si NMR of phosphorus-bearing organosilicon compounds with more than one phosphorus per molecule can take advantage of the presence of J-coupling nJ(31P29Si) for purposes of structural assignment from J-coupling patterns, conventional 29Si CP/MAS spectra of such molecular solids do not reveal structural details in a straightforward manner. For such compounds it is necessary to obtain 29Si CP/MAS spectra under conditions of simultaneous 1H- and 31P-high power decoupling in order to derive reliable 29Si chemical shift information. 29Si CP/MAS NMR spectra, obtained with and without 31P high power decoupling during the acquisition time, of several organosilicon compounds containing SixPy (x = 1-10, y = 1-10) moieties are reported.

Determination of 113Cd shielding tensor components in cadmium-phosphine complexes from 31P-decoupled 113Cd cross-polarisation/magic angle spinning spectra.

Owing to the simultaneous presence of various anisotropic interactions within the isolated M-31P and M(31P)2 fragments in solid transition metal phosphine complexes MX2.PR3 and MX2.2PR3 with, for instance, M = Cd, Hg or Pt, it is not normally possible to unequivocally determine the shielding tensor components of the metal nucleus M from simple 113Cd, 199Hg or 195Pt cross-polarisation/magic angle spinning (CP/MAS) spectra. In this paper it is shown that additional 31P on-resonance high-power decoupling during the acquisition time does allow the determination of the shielding tensor components of M from CP/MAS spectra. Two cadmium(II) complexes, Cd(OAc)2.Pchex3, (chex = cyclohexyl) and Cd(ClO4)2.2Pchex3 were chosen as examples; the 113Cd CP/MAS experiments were carried out at a low external magnetic field strength B0 = 2.35 T.

One- and two-dimensional 1H magic-angle spinning experiments on hydrous silicate glasses.

Applications of various one- and two-dimensional 1H magic-angle spinning nuclear magnetic resonance (MAS NMR) techniques for the elucidation of structural properties of hydrous silicate glasses are described. Advantages and limitations of one-dimensional experiments [MAS and combined rotation and multiple-puls spectroscopy (CRAMPS)] and of two-dimensional approaches (spin-exchange experiments, "MAS-CRAMPS" correlation plus extended versions) are discussed. The various 1H MAS NMR techniques are illustrated by practical examples of spectra obtained from a hydrous silicate glass of Na2O.4SiO2.0.7H2O composition.

[Chorionic biopsy in prenatal chromosome diagnosis]. / Chorionbiopsie in der pränatalen Chromosomendiagnostik.

This paper reports on 110 chromosome analyses of prenatal diagnosis after chorion biopsy. Normal findings were recorded in 105 cases (51 female, 54 male), and 5 chromosomic abnormalities were found, including triploidy, rarely to be observed in the second trimester, and a trisomy 8. Both direct preparation and long-term cultures were employed for chromosome diagnosis. With long-term cultures, three mosaic findings were recorded that were not confirmed in subsequent examinations of amniotic cells. The observation of certain cells with female karyotype in a long-term culture with otherwise definitely male karyotype illustrates the necessity of polymorphic comparison in order to exclude maternal contamination in the analysis of long-term cultures.