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Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting a growing number of elderly people. In order to improve the early and differential diagnosis of AD, better biomarkers are needed. Glycosylation is a protein post-translational modification that is modulated in the course of many diseases, including neurodegeneration. Aiming to improve AD diagnosis and differential diagnosis through glycan analytics methods, we report the glycoprotein glycome of cerebrospinal fluid (CSF) isolated from a total study cohort of 262 subjects. The study cohort consisted of patients with AD, healthy controls and patients suffering from other types of dementia. CSF free-glycans were also isolated and analyzed in this study, and the results reported for the first time the presence of 19 free glycans in this body fluid. The free-glycans consisted of complete or truncated N-/O-glycans as well as free monosaccharides. The free-glycans Hex 1 and HexNAc 1 Hex 1 Neu5Ac 1 were able to discriminate AD from controls and from patients suffering from other types of dementia. Regarding CSF N-glycosylation, high proportions of high-mannose, biantennary bisecting core-fucosylated N-glycans were found, whereby only about 20% of the N-glycans were sialylated. O-Glycans and free-glycan fragments were less sialylated in AD patients than in controls. To conclude, this comprehensive study revealed for the first time the biomarker potential of free glycans for the differential diagnosis of AD.

Patients with chronic kidney disease (CKD) have a high prevalence of hyperphosphatemia, where uremic toxins like inorganic phosphate (Pi) induce a cardiovascular remodeling. Related disorders like atherosclerosis bear the risk of increased morbidity and mortality. We previously found that Pi stimulates the synthesis and sulfation of the negatively charged glycosaminoglycans (GAGs) heparan sulfate and chondroitin sulfate in vascular smooth muscle cells (VSMC). Similar GAG alterations were detected in VSMC-derived exosome-like extracellular vesicles (EV). These EV showed a strong interaction with very small superparamagnetic iron oxide particles (VSOP), which are used as imaging probes for experimental magnetic resonance imaging (MRI). Hyaluronic acid (HA) represents another negatively charged GAG which is supposed to function as binding motif for VSOP as well. We investigated the effects of Pi on the amounts of HA in cells and EV and studied the HA-dependent interaction between VSOP with cells and EV. Rat VSMC were treated with elevated concentrations of Pi. CKD in rats was induced by adenine feeding. EV were isolated from culture supernatants and rat plasma. We investigated the role of HA in binding VSOP to cells and EV via cell-binding studies, proton relaxometry, and analysis of cellular signaling, genes, proteins, and HA contents. Due to elevated HA contents, VSMC and EV showed an increased interaction with VSOP after Pi stimulation. Amongst others, Pi induced hyaluronan synthase (HAS)2 expression and activation of the Wnt pathway in VSMC. An alternative upregulation of HA by iloprost and an siRNA-mediated knockdown of HAS2 confirmed the importance of HA in cells and EV for VSOP binding. The in vitro-derived data were validated by analyses of plasma-derived EV from uremic rats. In conclusion, the inorganic uremic toxin Pi induces HA synthesis in cells and EV, which leads to an increased interaction with VSOP. HA might therefore be a potential molecular target structure for improved detection of pathologic tissue changes secondary to CKD like atherosclerosis or cardiomyopathy using EV, VSOP and MRI.

It remains uncertain how brain glycosaminoglycans (GAGs) contribute to the progression of inflammatory disorders like multiple sclerosis (MS). We investigated here neuroinflammation-mediated changes in GAG composition and metabolism using the mouse model of experimental autoimmune encephalomyelitis (EAE) and sham-immunized mice as controls. Cerebellum, mid- and forebrain at different EAE phases were investigated using gene expression analysis (microarray and RT-qPCR) as well as HPLC quantification of CS and hyaluronic acid (HA). The cerebellum was the most affected brain region showing a downregulation of Bcan, Cspg5, and an upregulation of Dse, Gusb, Hexb, Dcn and Has2 at peak EAE. Upregulation of genes involved in GAG degradation as well as synthesis of HA and decorin persisted from onset to peak, and diminished at remission, suggesting a severity-related decrease in CS and increments in HA. Relative disaccharide quantification confirmed a 3.6 % reduction of CS-4S at peak and a normalization during remission, while HA increased in both phases by 26.1 % and 17.6 %, respectively. Early inflammatory processes led to altered GAG metabolism in early EAE stages and subsequent partially reversible changes in CS-4S and in HA. Targeting early modifications in CS could potentially mitigate progression of EAE/MS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background and Objectives : The aim of the study was to analyze the prevalence and characteristics of pancreatic cystic tumors (PCTs). Material and Methods : A retrospective analysis of the medical records of 124 patients, 102 (69%) women and 46 (31%) men, who had undergone surgery for pancreatic cystic tumors in 2014-2018. Among 148 pancreatic cysts, 24 (16%) were non-neoplasmatic and 124 (84%) were neoplasmatic. The neoplasmatic cysts ( n = 124) were included in our analysis. There were five main types of PCTs: IPMN (intraductal papillary mucinous neoplasm) ( n = 45), MCN (mucinous cystic neoplasm) ( n = 30), SCN (serous cystic neoplasm) ( n = 28), SPN (solid pseudopapillary neoplasm) ( n = 8), and CPEN (cystic pancreatic endocrine neoplasm) ( n = 8), as well as mixed-type tumors ( n = 5). Results: A statistically significant dependency between PCT type and age was proven ( p = 0.0001): IPMNs were observed in the older group of patients with an average age of 66.12 (40-79) years while SPNs were noted in the youngest group of patients with an average age of 36.22 (22-55) years. A statistically significant association between PCT type and gender ( p = 0.0001) was found: IPMNs occurred among 24 (53.33%) men and 21 (46.6%) women. In the MCN and SPN groups, all patients were female (100%). Among the SCN group, the majority were women (27 (96.43%)), and there was only 1 (3.57%) man. A statistically significant dependency between PCT type and size was proven ( p = 0.0007). The mean size of IPMNs was the smallest 2.95 (0.6-10 cm) and the mean size of MCNs was the largest 6.78 (1.5-19 cm). A statistically significant dependency between PCT type and tumor location was proven ( p = 0.000238). The most frequent location of IPMN was the pancreatic head: 27 (60%). MCN was most frequently located in the pancreatic tail (18 (60%)). Most (10/28) SCNs were found in the pancreatic tail (10 (35.71%)). CPENs were most frequently located in the pancreatic tail (three (37.5%)) and pancreatic body and tail (three (37.5%)). SPNs were located commonly in the pancreatic head (five (62.5%)). The type of surgery depended on the tumor location. The most frequent surgery for IPMNs was pancreatoduodenectomy (44.4%), while for MCNs and SCNs, it was distal pancreatectomy (81%). The postoperative morbidity and mortality were 34.68% and 1.61%, respectively. Postoperative pancreatic fistula (POPF) was the most frequent (29%) complication. Conclusions : IPMN was the most frequent resected PCT in our material. A statistically significant association between the type of cyst and location within the pancreas, size, local lymph node involvement, and patient's age and sex was proved. POPF was the most frequent postoperative complication. In patients with PCTs, due to substantial postoperative morbidity, adequate patient selection, considering both the surgical risk as well as the long-term risk of malignant transformation, is very important during qualification for surgery.

Inflammatory bowel diseases (IBD) comprise mainly ulcerative colitis (UC) and Crohn´s disease (CD). Both forms present with a chronic inflammation of the (gastro) intestinal tract, which induces excessive changes in the composition of the associated extracellular matrix (ECM). In UC, the inflammation is limited to the colon, whereas it can occur throughout the entire gastrointestinal tract in CD. Tools for early diagnosis of IBD are still very limited and highly invasive and measures for standardized evaluation of structural changes are scarce. To investigate an efficient non-invasive way of diagnosing intestinal inflammation and early changes of the ECM, very small superparamagnetic iron oxide nanoparticles (VSOPs) in magnetic resonance imaging (MRI) were applied in two mouse models of experimental colitis: the dextran sulfate sodium (DSS)-induced colitis and the transfer model of colitis. For further validation of ECM changes and inflammation, tissue sections were analyzed by immunohistochemistry. For in depth ex-vivo investigation of VSOPs localization within the tissue, Europium-doped VSOPs served to visualize the contrast agent by imaging mass cytometry (IMC). VSOPs accumulation in the inflamed colon wall of DSS-induced colitis mice was visualized in T 2 * weighted MRI scans. Components of the ECM, especially the hyaluronic acid content, were found to influence VSOPs binding. Using IMC, co-localization of VSOPs with macrophages and endothelial cells in colon tissue was shown. In contrast to the DSS model, colonic inflammation could not be visualized with VSOP-enhanced MRI in transfer colitis. VSOPs present a potential contrast agent for contrast-enhanced MRI to detect intestinal inflammation in mice at an early stage and in a less invasive manner depending on hyaluronic acid content., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Golusda, Kühl, Lehmann, Dahlke, Mueller, Boehm-Sturm, Saatz, Traub, Schnorr, Freise, Taupitz, Biskup, Blanchard, Klein, Sack, Siegmund and Paclik.)

Glycosaminoglycans (GAGs) are considered to be the most difficult type of glycoconjugates to analyze as they are constituted of linear long polysaccharidic chains having molecular weights reaching up to several million daltons. Bottom-up analysis of glycosaminoglycans from biological samples is a long and work-extensive procedure due to the many preparation steps involved. In addition, so far, only few research articles have been dedicated to the analysis of GAGs by means of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) because their intact ionization can be problematic due to the presence of labile sulfate groups. In this work, we had the aim of exploring the sulfation pattern of monosulfated chondroitin/dermatan sulfate (CS/DS) disaccharides in human tissue samples because they represent the most abundant form of sulfation in disaccharides. We present here an optimized strategy to analyze on-target derivatized CS/DS disaccharides via MALDI-TOF-MS using a fast workflow that does not require any purification after enzymatic cleavage. For the first time, we show that MALDI-TOF/TOF experiments allow for discrimination between monosulfated CS disaccharide isomers via specific fragments corresponding to glycosidic linkages and to cross-ring cleavages. This proof of concept is illustrated via the analysis of CS/DS disaccharides of atherosclerotic lesions of different histological origins, in which we were able to identify their monosulfation patterns.

Glycoconjugates on extracellular vesicles (EVs) play a vital role in internalization and mediate interaction as well as regulation of the host immune system by viruses, bacteria, and parasites. During their intraerythrocytic life-cycle stages, malaria parasites, Plasmodium falciparum ( Pf ) mediate the secretion of EVs by infected red blood cells (RBCs) that carry a diverse range of parasitic and host-derived molecules. These molecules facilitate parasite-parasite and parasite-host interactions to ensure parasite survival. To date, the number of identified Pf genes associated with glycan synthesis and the repertoire of expressed glycoconjugates is relatively low. Moreover, the role of Pf glycans in pathogenesis is mostly unclear and poorly understood. As a result, the expression of glycoconjugates on Pf -derived EVs or their involvement in the parasite life-cycle has yet to be reported. Herein, we show that EVs secreted by Pf -infected RBCs carry significantly higher sialylated complex N -glycans than EVs derived from healthy RBCs. Furthermore, we reveal that EV uptake by host monocytes depends on N-glycoproteins and demonstrate that terminal sialic acid on the N -glycans is essential for uptake by human monocytes. Our results provide the first evidence that Pf exploits host sialylated N -glycans to mediate EV uptake by the human immune system cells., (© 2022 The Authors. Journal of Extracellular Biology published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Glycosaminoglycans are long polysaccharidic chains, which are mostly present in connective tissues. Modified GAG expression in tissues surrounding malignant cells has been shown to contribute to tumor progression, aggressive status and metastasis in many types of cancer. Ovarian cancer is one of the most lethal gynecological malignancies due to its late diagnosis because of the absence of clear symptoms and unavailability of early disease markers. We investigated for the first time GAG changes at the molecular level as a novel biomarker for primary epithelial ovarian cancer. To this end, serum of a cohort of 68 samples was digested with chondroitinase ABC, which releases chondroitin sulfate into disaccharides. After labeling and purification, they were measured by HPLC, yielding a profile of eight disaccharides. We proposed a novel GAG-based score named "CS- bio" from the measured abundance of disaccharides present that were of statistical relevance. CS-bio's performance was compared with CA125, the clinically used serum tumor marker in routine diagnostics. CS-bio had a better sensitivity and specificity than CA125. It was more apt in differentiating early-stage patients from healthy controls, which is of high interest for oncologists.

GDP-mannose-pyrophosphorylase-B (GMPPB) facilitates the generation of GDP-mannose, a sugar donor required for glycosylation. GMPPB defects cause muscle disease due to hypoglycosylation of α-dystroglycan (α-DG). Alpha-DG is part of a protein complex, which links the extracellular matrix with the cytoskeleton, thus stabilizing myofibers. Mutations of the catalytically inactive homolog GMPPA cause alacrima, achalasia, and mental retardation syndrome (AAMR syndrome), which also involves muscle weakness. Here, we showed that Gmppa-KO mice recapitulated cognitive and motor deficits. As structural correlates, we found cortical layering defects, progressive neuron loss, and myopathic alterations. Increased GDP-mannose levels in skeletal muscle and in vitro assays identified GMPPA as an allosteric feedback inhibitor of GMPPB. Thus, its disruption enhanced mannose incorporation into glycoproteins, including α-DG in mice and humans. This increased α-DG turnover and thereby lowered α-DG abundance. In mice, dietary mannose restriction beginning after weaning corrected α-DG hyperglycosylation and abundance, normalized skeletal muscle morphology, and prevented neuron degeneration and the development of motor deficits. Cortical layering and cognitive performance, however, were not improved. We thus identified GMPPA defects as the first congenital disorder of glycosylation characterized by α-DG hyperglycosylation, to our knowledge, and we have unraveled underlying disease mechanisms and identified potential dietary treatment options.

The classical function of human chorionic gonadotropin (hCG) is its role in supporting pregnancy. hCG is a dimer consisting of two highly glycosylated subunits, alpha (CGA) and beta (CGB). The beta-hCG protein is encoded by CGB3, CGB5, CGB7 and CGB8 genes. CGB3, 5 and 8 code for an identical protein, CGB3/5/8, whereas CGB7 differs in three amino acids from CGB3/5/8. We had observed earlier that CGB7 and CGB3/5/8 display very distinct tissue expression patterns and that the tumor suppressor and transcription factor p53 can activate expression of CGB7 but not of CGB3/5/8 genes. Here, we investigate the glycan structures and possible functional differences of the two CGB variants. To this end, we established a system to produce and isolate recombinant CGA, CGB7 and CGB3/5/8 proteins. We found that N- and O-glycosylation patterns of CGB7 and CGB3/5/8 are quite similar. Functional assays were performed by testing activation of the ERK1/2 pathway and demonstrated that CGB7 and CGB5/5/8 appear to be functionally redundant isoforms, although a slight difference in the kinetics of ERK1/2 pathway activation was observed. This is the first time that biological activity of CGB7 is shown. In summary, the results lead to the hypothesis that CGB7 and CGB3/5/8 do not hold significant functional differences but that timing and cell type of their expression is the key for understanding their divergent evolution.

Epithelial ovarian cancer (EOC) is worldwide the sixth most lethal form of cancer occurring in women. More than one third of ovarian patients have ascites at the time of diagnosis and almost all of them have it when recurrence occurs. Although its effect on tumor cell microenvironment remains poorly understood, its presence is correlated with bad diagnosis. In previous studies, we proposed a novel glycan-based biomarker for the diagnosis of EOC, which showed an improved sensitivity and specificity at any stage of the disease and an improved discrimination between malignant and benign ovarian tumors. In this work, we report for the first time the N-glycome profiles of ascitic fluid from primary serous EOC patients and compare them with the serum N-glycomes of the same patients as well as of healthy controls. N-Glycans were digested from equivalent amount of ascites and serum from 18 EOC patients and from serum of 20 age-matched controls and measured by MALDI-TOF-MS. Ascites N-glycome showed increased antennarity, branching, sialylation and Lewis X motives compared to healthy serum. In addition, a correlation was established between ascites volume and degree of sialylation., Significance: Malignant ascitic fluid is the build-up of large volumes of fluid in the peritoneal cavity secondary to cancer. At least one-third of ovarian cancer patients develop ascites, a generally voluminous fluid containing cells of tumor origin, in the course of cancer and almost all when recurrence occurs. The proteome of ascites is known to be as complex as that of serum and contains high amount of proteins shed from inflammatory cells as well as from tumor cells. Although many attempts have been made to provide molecular insight into the proteomic and peptidomic content of malignant ascites, no data about the N-glycome of the ascitic fluid fraction from cancer patients has been reported to date. In this study, the N-glycosylation profile of ascites from 20 patients suffering from epithelial ovarian cancer (EOC) was analyzed by MALDI-TOF-mass spectrometry and compared to the pathologically modified N-glycan pattern obtained from serum of the same patients as well as to the pattern of serum from healthy individuals. Significant quantitative differences were observed in the ascites of EOC patients when compared to the serum of healthy subjects. The glycome of ascites shows typical features of inflammatory conditions, what was also found in the serum of patients suffering from EOC when compared to healthy serum. In addition, a correlation was established between ascites volume and degree of sialylation, showing that the high-volume ascites contains a higher amount of sialylated structures than the low-volume ascites., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Head and neck squamous cell carcinomas (HNSCC) exhibiting resistance to the EGFR-targeting drug cetuximab poses a challenge to their effective clinical management. Here, we report a specific mechanism of resistance in this setting based upon the presence of a single nucleotide polymorphism encoding EGFR-K 521 (K-allele), which is expressed in >40% of HNSCC cases. Patients expressing the K-allele showed significantly shorter progression-free survival upon palliative treatment with cetuximab plus chemotherapy or radiation. In several EGFR-mediated cancer models, cetuximab failed to inhibit downstream signaling or to kill cells harboring a high K-allele frequency. Cetuximab affinity for EGFR-K 521 was reduced slightly, but ligand-mediated EGFR activation was intact. We found a lack of glycan sialyation on EGFR-K 521 that associated with reduced protein stability, suggesting a structural basis for reduced cetuximab efficacy. CetuGEX, an antibody with optimized Fc glycosylation targeting the same epitope as cetuximab, restored HNSCC sensitivity in a manner associated with antibody-dependent cellular cytotoxicity rather than EGFR pathway inhibition. Overall, our results highlight EGFR-K 521 expression as a key mechanism of cetuximab resistance to evaluate prospectively as a predictive biomarker in HNSCC patients. Further, they offer a preclinical rationale for the use of ADCC-optimized antibodies to treat tumors harboring this EGFR isoform. Cancer Res; 77(5); 1188-99. ©2016 AACR ., (©2016 American Association for Cancer Research.)

Many biologically relevant glycoproteins need to be separated on 1D- or 2D-gels prior to analysis and are available in picomole amounts. Therefore, it is important to have optimized methods to unravel the glycome that combine in-gel digestions with MALDI-TOF-MS. In this technical report, we investigated how the detection of in-gel released N-glycans could be improved by MALDI-TOF-MS. First, an AnchorChip target was tested and compared to ground steel target using several reference oligosaccharides. The highest signals were obtained with an AnchorChip target and D-arabinosazone as the matrix; a LOD of 1.3 to 10 fmol was attained. Then, the effect of octyl-β-glucopyranoside, a nonionic detergent, was studied during in-gel peptide-N(4) -(acetyl-ß-glucosaminyl) asparagine amidase F digestion of standard glycoproteins and during glycan extraction. Octyl-β-glucopyranoside increased the intensity and the amount of detected neutral as well as acidic N-glycans. A LOD of under 7 pmol glycoprotein could be achieved., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Epithelial ovarian cancer (EOC) is the sixth most common cause of cancer deaths in women because the diagnosis occurs mostly when the disease is in its late-stage. Current diagnostic methods of EOC show only a moderate sensitivity, especially at an early-stage of the disease; hence, novel biomarkers are needed to improve the diagnosis. We recently reported that serum glycome modifications observed in late-stage EOC patients by MALDI-TOF-MS could be combined as a glycan score named GLYCOV that was calculated from the relative areas of the 11 N-glycan structures that were significantly modulated. Here, we evaluated the ability of GLYCOV to recognize early-stage EOC in a cohort of 73 individuals comprised of 20 early-stage primary serous EOC, 20 benign ovarian diseases (BOD), and 33 age-matched healthy controls. GLYCOV was able to recognize stage I EOC whereas CA125 values were statistically significant only for stage II EOC patients. In addition, GLYCOV was more sensitive and specific compared to CA125 in distinguishing early-stage EOC from BOD patients, which is of high relevance to clinicians as it is difficult for them to diagnose malignancy prior to operation.

During the development of cancer, changes in cellular glycosylation are observed, indicating that alterations of the glycome occur in extracellular fluids as well as in serum and could therefore serve as tumor biomarkers. In the case of epithelial ovarian cancer (EOC), common tumor markers such as CA125 are known to have poor specificity; therefore, better biomarkers are needed. The aim of this work was to identify new potential glycan biomarkers in EOC-patients. N-Glycans were cleaved from serum glycoproteins from 63 preoperative primary EOC-patients along with 33 age-matched healthy women, permethylated, and analyzed using MALDI-TOF mass spectrometry. A value named GLYCOV was calculated from the relative areas of the 11 N-glycan biomarkers revealed by SPSS statistical analyses, namely four high-mannose and seven complex-type fucosylated N-glycans. GLYCOV diagnosed primary EOC with a sensitivity of 97% and a specificity of 98.4% whereas CA-125 showed a sensitivity of 97% and a specificity of 88.9%. Our study is the first one to compare glycan values with the established tumor marker CA125 and to give better results. Therefore, the N-glycome could potentially be used as a biomarker.

During the last years, the use of therapeutic glycoproteins has increased strikingly. Glycosylation of recombinant glycoproteins is of major importance in biotechnology, as the glycan composition of recombinant glycoproteins impacts their pharmacological properties. The terminal position of N-linked complex glycans in mammals is typically occupied by sialic acid. The presence of sialic acid is crucial for functionality and affects the half-life of glycoproteins. However, glycoproteins in the bloodstream become desialylated over time and are recognized by the asialoglycoprotein receptors via the exposed galactose and targeted for degradation. Non-natural sialic acid precursors can be used to engineer the glycosylation side chains by biochemically introducing new non-natural terminal sialic acids. Previously, we demonstrated that the physiological precursor of sialic acid (i.e., N-acetylmannosamine) can be substituted by the non-natural precursors N-propanoylmannosamine (ManNProp) or N-pentanoylmannosamine (ManNPent) by their simple application to the cell culture medium. Here, we analyzed the glycosylation of erythropoietin (EPO). By feeding cells with ManNProp or ManNPent, we were able to incorporate N-propanoyl or N-pentanoyl sialic acid in significant amounts into EPO. Using a degradation assay with sialidase, we observed a higher resistance of EPO to sialidase after incorporation of N-propanoyl or N-pentanoyl sialic acid.

The televisite is a form of application of telemedicine, that allows a communication between the patient and the family doctor or specialist in the clinic after discharging of hospital. Pioneers for the use of telematic projects have been up to now wide states like the USA, Canada, Norway or Australia to provide, guarantee and maintain by the means of telemedical solutions medical care in geographic regions hardly reachable and of little medical attention. In central Europe and Germany telemedicine is gaining in significance on the one hand because of increasing importance of the cost factor and resulting pressure on the public health system and on the other hand because of the rising demand of the patients for optimised medical care. It specially represents a new form of treatment in patients care after dischargement of hospital. In the year of 2002 a prospective randomised two-armed study was initiated including patients after operative intervention by arthroplasty in posttraumatic contracture of the elbow. The system of the Televisite is used for 6 weeks after dischargement and patients had been controlled ambulant after 6 months including a physical examination. The functional outcome will be scored, the duration of stay in hospital measured, the arising costs for treatment calculated and the satisfaction of the patients in handling the Televisite surveyed. Over this first results showed a shortened stay in hospital together with lowered costs in medical treatment on the one hand and on the other no difference in functional outcome could be found in comparison to the control group by additionally high grade of satisfaction with the new system.

The TELTRA Televisite is a remote patient monitoring system, allowing the patient to remain at home and deliver monitoring data, images, speech and video recordings to the doctor. From this point, all the above mentioned sources of information will be referred to as data. As a medium for the information transfer, the Televisite uses ISDN or multi-channel HSCSD telephone. The system software architecture consists of the design of graphics patient interface, gathering and processing of data, transmittal of data and most importantly, providing highest security at all stages of the data, between patient and database server. The system also provides facility for emergency telephony between the patient and the physician. The technology employed in the Televiste is based on store and forward, where data is first collected and sent to the doctor at the end of a teleround session.

The Televisite application is a post-stationary consulting method, whose main aim is to reduce the treatment time of inpatients. It provides a high quality home consultation after the patient has been discharged from the hospital. The technical handling and the validity of the new method of caring will be analysed--particularly the human-machine interface. In a prospective study case injured patients were attend using the Televisite. For communications with the consulting doctor they were supplied with a high resolution digital camera and a mobile PC with an integrated HCSCD cell phone. The doctor examined the data transmitted by the patient and remotely consulted the patient using the Televisite. Through a simple self-explaining user interface, a smooth information transfer was guaranteed.