Maliha Sadick

Publications of Maliha Sadick

• First multimodal embolization particles visible on x-ray/computed tomography and magnetic resonance imaging.

  Authors: Soenke H Bartling, Johannes Budjan, Hagit Aviv, Stefan Haneder, Bettina Kraenzlin, Henrik Michaely, Shlomo Margel, Steffen Diehl, Wolfhard Semmler, Norbert Gretz, Stefan O Schönberg, Maliha Sadick

  Investigative radiology. 03/2011; 46(3):178-86.

  Embolization therapy is gaining importance in the treatment of malignant lesions, and even more in benign lesions. Current embolization materials are not visible in imaging modalities. However, it isEmbolization therapy is gaining importance in the treatment of malignant lesions, and even more in benign lesions. Current embolization materials are not visible in imaging modalities. However, it is assumed that directly visible embolization material may provide several advantages over current embolization agents, ranging from particle shunt and reflux prevention to improved therapy control and follow-up assessment. X-ray- as well as magnetic resonance imaging (MRI)-visible embolization materials have been demonstrated in experiments. In this study, we present an embolization material with the property of being visible in more than one imaging modality, namely MRI and x-ray/computed tomography (CT). Characterization and testing of the substance in animal models was performed. To reduce the chance of adverse reactions and to facilitate clinical approval, materials have been applied that are similar to those that are approved and being used on a routine basis in diagnostic imaging. Therefore, x-ray-visible Iodine was combined with MRI-visible Iron (Fe3O4) in a macroparticle (diameter, 40-200 μm). Its core, consisting of a copolymerized monomer MAOETIB (2-methacryloyloxyethyl [2,3,5-triiodobenzoate]), was coated with ultra-small paramagnetic iron oxide nanoparticles (150 nm). After in vitro testing, including signal to noise measurements in CT and MRI (n = 5), its ability to embolize tissue was tested in an established tumor embolization model in rabbits (n = 6). Digital subtraction angiography (DSA) (Integris, Philips), CT (Definition, Siemens Healthcare Section, Forchheim, Germany), and MRI (3 Tesla Magnetom Tim Trio MRI, Siemens Healthcare Section, Forchheim, Germany) were performed before, during, and after embolization. Imaging signal changes that could be attributed to embolization particles were assessed by visual inspection and rated on an ordinal scale by 3 radiologists, from 1 to 3. Histologic analysis of organs was performed. Particles provided a sufficient image contrast on DSA, CT (signal to noise [SNR], 13 ± 2.5), and MRI (SNR, 35 ± 1) in in vitro scans. Successful embolization of renal tissue was confirmed by catheter angiography, revealing at least partial perfusion stop in all kidneys. Signal changes that were attributed to particles residing within the kidney were found in all cases in all the 3 imaging modalities. Localization distribution of particles corresponded well in all imaging modalities. Dynamic imaging during embolization provided real-time monitoring of the inflow of embolization particles within DSA, CT, and MRI. Histologic visualization of the residing particles as well as associated thrombosis in renal arteries could be performed. Visual assessment of the likelihood of embolization particle presence received full rating scores (153/153) after embolization. Multimodal-visible embolization particles have been developed, characterized, and tested in vivo in an animal model. Their implementation in clinical radiology may provide optimization of embolization procedures with regard to prevention of particle misplacement and direct intraprocedural visualization, at the same time improving follow-up examinations by utilizing the complementary characteristics of CT and MRI. Radiation dose savings can also be considered. All these advantages could contribute to future refinements and improvements in embolization therapy. Additionally, new approaches in embolization research may open up.

• Transcutaneous assessment of renal function in conscious rats with a device for measuring FITC-sinistrin disappearance curves.

  Authors: Daniel Schock-Kusch, Qing Xie, Yury Shulhevich, Juergen Hesser, Dzmitry Stsepankou, Maliha Sadick, Stefan Koenig, Friederike Hoecklin, Johannes Pill, Norbert Gretz

  Kidney international. 03/2011; 79(11):1254-8.

  Determination of the urinary or plasma clearance of exogenous renal markers, such as inulin or iohexol, is considered to be the gold standard for glomerular filtration rate (GFR) measurement. Here,Determination of the urinary or plasma clearance of exogenous renal markers, such as inulin or iohexol, is considered to be the gold standard for glomerular filtration rate (GFR) measurement. Here, we describe a technique allowing determination of renal function based on transcutaneously measured elimination kinetics of fluorescein isothiocyanate (FITC)-sinistrin, the FITC-labeled active pharmaceutical ingredient of a commercially available marker of GFR. A low cost device transcutaneously excites FITC-sinistrin at 480  nm and detects the emitted light through the skin at 520  nm. A radio-frequency transmission allows remote monitoring and real-time analysis of FITC-sinistrin excretion as a marker of renal function. Due to miniaturization, the whole device fits on the back of freely moving rats, and requires neither blood sampling nor laboratory assays. As proof of principle, comparative measurements of transcutaneous and plasma elimination kinetics of FITC-sinistrin were compared in freely moving healthy rats, rats showing reduced kidney function due to unilateral nephrectomy and PKD/Mhm rats with cystic kidney disease. Results show highly comparable elimination half-lives and GFR values in all animal groups. Bland-Altman analysis of enzymatically compared with transcutaneously measured GFR found a mean difference (bias) of 0.01 and a -0.30 to 0.33 ml/min per 100 g body weight with 95% limit of agreement. Thus, with this device, renal function can be reliably measured in freely moving rats eliminating the need for and influence of anesthesia on renal function.

• Two non-invasive GFR-estimation methods in rat models of polycystic kidney disease: 3.0 Tesla dynamic contrast-enhanced MRI and optical imaging.

  Authors: Maliha Sadick, Ulrike Attenberger, Bettina Kraenzlin, Hany Kayed, Stefan O Schoenberg, Norbert Gretz, Daniel Schock-Kusch

  Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 03/2011; 26(10):3101-8.

  The aim of this study was the assessment of kidney morphology and glomerular filtration rate (GFR) in rat models of polycystic kidney disease and a healthy control group of Sprague-Dawley rats (SDThe aim of this study was the assessment of kidney morphology and glomerular filtration rate (GFR) in rat models of polycystic kidney disease and a healthy control group of Sprague-Dawley rats (SD rats). The performance of two non-invasive GFR estimation methods-3.0 Tesla magnetic resonance imaging (MRI) and optical imaging were investigated. Data of GFR assessment was compared to surrogate markers of kidney function and renal histology. Optical imaging of GFR was performed transcutaneously in a small animal imaging system with the fluorescent renal marker fluorescein-isothiocyanate-labelled-sinistrin. Morphologic and dynamic renal imaging was done on a clinical 3.0T MR scanner. Renal perfusion analysis was performed with a two-compartment filtration model. The healthy SD rats showed physiological levels of creatinine and urea, indicating normal kidney function. These parameters were elevated in the small animal groups of polycystic kidney disease. For the calculation of perfusion and filtration parameters of kidney function in MRI, a 2D turbo FLASH sequence was performed and allowed to distinguish between normal GFR of healthy rats and reduced GFR of rats with polycystic kidney disease. Also, MRI GFR varied among two different rat strains of polycystic kidney disease, according to their status of renal function impairment. Optical imaging GFR confirmed higher GFR values in healthy rats compared to ill rats but did not show different results among the two rat strains of polycystic kidney disease. For this reason, MRI and optical imaging GFR estimation presented an intra-method bias. Both non-invasive estimation methods of GFR, MRI and optical imaging, can differentiate between healthy rats and animals with limited kidney function. Furthermore, optical imaging, unlike MRI, seems to consider that disease progression with increase of renal polycystic deterioration does not correlate with decrease of GFR in the initial stage of compensatory hyperfiltration.

• Application of DC beads in hepatocellular carcinoma: clinical and radiological results of a drug delivery device for transcatheter superselective arterial embolization.

  Authors: Maliha Sadick, Stephan Haas, Matthias Loehr, Mohammad Elshwi, Manfred V Singer, Joachim Brade, Stefan O Schoenberg, Steffen J Diehl

  Onkologie. 01/2010; 33(1-2):31-7.

  Application of a drug delivery device for transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Clinical and radiological treatment assessment. 24 patients withApplication of a drug delivery device for transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Clinical and radiological treatment assessment. 24 patients with liver cirrhosis and uni- or multifocal HCC underwent TACE with doxorubicin beads (DC Bead). The underly-ing cause of liver cirrhosis was hepatitis (A: n = 7; B: n = 10) or alcohol consumption (n = 7). Patients presented with Child Pugh stage A (n = 15) and B (n = 9). The mean intrahepatic tumor size, considering the sum of diameters of all lesions treated, was 3.83 cm (+/-2.4). Liver function and hematological parameters were documented before and after each TACE. Magnetic resonance imaging (MRI) was performed before and 4 weeks after TACE. The T1-w 3D volume-interpolated breathhold exam (VIBE) sequence was applied for evaluation of the therapy response. 24 patients received a total number of 69 TACE treatments with DC beads (mean dose 160 mg). The elevation of liver function parameters after treatment did not affect the patients' clinical condition. The T1-w VIBE sequence proved very valuable for assessment of the intrahepatic tumor spread. Post-contrast images enabled delineation of the viable HCC lesions, hence facilitating the selective transcatheter approach. The tumor marker a-fetoprotein (AFP), available in 19/24 patients, dropped from 347.5 to 299.5 ng/ml, without being a reliable predictor of treatment response. A decrease of tumor size after TACE from 3.83 (+/-2.40) to 3.01 cm (+/-2.67; p < 0.0001) was evident on the T1w-VIBE sequences. The mean follow-up period was 30 months. At the time of data analysis, 10 (42%) out of 14 patients were alive. TACE with DC beads in HCC offers a safe and efficient treatment resulting in tumor response within a very short time.

• Morphologic and Dynamic Renal Imaging With Assessment of Glomerular Filtration Rate in a pcy-Mouse Model Using a Clinical 3.0 Tesla Scanner.

  Authors: Maliha Sadick, Daniel Schock, Bettina Kraenzlin, Norbert Gretz, Stefan Schoenberg, Henrik Michaely

  Investigative radiology. 06/2009;

  OBJECTIVE:: Morphologic and dynamic renal imaging is necessary for characterization of kidney function in renal insufficiency. Assessment of renal perfusion and the glomerular filtration rate (GFR)OBJECTIVE:: Morphologic and dynamic renal imaging is necessary for characterization of kidney function in renal insufficiency. Assessment of renal perfusion and the glomerular filtration rate (GFR) are essential, as the serum creatinine level and urea are not sensitive at an early stage of kidney damage. Currently available GFR estimation methods are time consuming, expensive, and lead to radiation exposure for the patient. Therefore, the aim was to determine the feasibility of morphologic and contrast-enhanced dynamic magnetic resonance imaging for GFR assessment in pcy (polycystic kidneys and fibrosis) mice, using a clinical 3.0 Tesla scanner. MATERIALS AND METHODS:: Fourteen pcy-mice were anesthetized and an internal jugular vein catheter was implanted to which a dedicated extension tube with a 0.28 mm inner diameter was connected, filled with 1:100 muL diluted gadobutrol (Gadovist Bayer Schering Pharma, Berlin, Germany). Imaging of the mice was performed with a dedicated 8-element mouse coil (Rapid Biomedical, Rimpar, Germany) plugged into a clinical 32-channel 3.0 Tesla magnetic resonance-scanner (Magnetom Verio, Siemens Medical Solution, Erlangen, Germany). In this study, different morphologic sequences comprising a T1-w 3D volume-interpolated breathhold examination, T2-w 2D half-Fourier acquired turbo spin echo (HASTE), T2-w 2D BLADE-TSE with fat saturation, and a T2-w 3D SPACE were acquired. The dynamic sequence performed for assessment of GFR, was a 2D SR-Turbo FLASH sequence. Image analysis and data assessment was performed by 2 radiologists who were experienced in assessment of human kidney disease. A 3-point scale for visual assessment of renal cystic changes in the pcy-mice was applied. The appearance of cysts, considering a detailed demarcation of the cyst with an enhancing rim and a hypointense core, were assessed as detailed: (1) faint (2) and not to be differentiated, (3) findings in the morphologic sequences. Quantitative parameters of renal function (cortex plasma flow mL/100 mL/min, cortex plasma volume mL/100 mL, and PT sec) were fitted to a 2-compartment model and compared with blood samples of creatinine and urea. Histologic progression of cysts and fibrosis in the pcy-mice was analyzed. RESULTS:: The T2-w 3D SPACE and T1-w 3D volume-interpolated breathhold examination sequence post contrast with thinnest slice thickness of 1 to 1.2 mm were well suited for delineation of the kidneys with detailed demarcation of the cysts (image quality score: 1.14 +/- 0.37 and 1.2 +/- 0.70, respectively). The T2-w 2D BLADE-TSE proved feasible, too (image quality score: 1.28 +/- 0.59). The T2-w 2D HASTE sequence with minimally achievable slice thickness of 2 mm was not suitable for morphologic assessment (image quality score: 2.9 +/- 0.37). The HASTE sequence suffered from blurring artifacts which further decreased the conspicuity of small cystic changes. The 2D SR-Turbo FLASH sequence showed the renal first pass of the contrast agent and enabled assessment of GFR. The data after time resolved 2D SR-Turbo FLASH perfusion analysis was used for GFR evaluation and demonstrated better GFR values in the young pcy-mice (0.558 mL/min) compared with the older pcy-mice (0.066 mL/min). CONCLUSION:: Application of dedicated coils with a clinical 3.0 Tesla magnetic resonance-scanner have proved feasible for morphologic and dynamic renal imaging with assessment of GFR in pcy-mice.

• Transcutaneous measurement of glomerular filtration rate using FITC-sinistrin in rats.

  Authors: Daniel Schock-Kusch, Maliha Sadick, Nadja Henninger, Bettina Kraenzlin, Guenter Claus, Hans-Martin Kloetzer, Christel Weiß, Johannes Pill, Norbert Gretz

  Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 05/2009;

  BACKGROUND: Inulin/sinistrin (I/S) clearance is a gold standard for an accurate assessment of glomerular filtration rate (GFR). Here we describe and validate an approach for a transcutaneousBACKGROUND: Inulin/sinistrin (I/S) clearance is a gold standard for an accurate assessment of glomerular filtration rate (GFR). Here we describe and validate an approach for a transcutaneous determination of GFR by using fluorescein-isothiocyanate-labelled sinistrin (FITC-S) in rats. METHODS: Using a small animal imager, fluorescence is measured over the depilated ear of a rat after the injection of FITC-S. The decay curve of fluorescence is used for the calculation of half-life and GFR. The thus obtained transcutaneous data were validated by simultaneously performed enzymatic and fluorometric measurements in plasma of both FITC-S and sinistrin. RESULTS: The results of enzymatic sinistrin determination versus transcutaneous half-life of FITC-S or plasma fluorescence correlated well with each other (R(2) > 0.90). Furthermore, Bland-Altman analyses proved a good degree of agreement of the three methods used. The measurements performed in healthy animals as well as different models of renal failure demonstrate its appropriateness in a wide range of renal function. CONCLUSIONS: The transcutaneous method described offers a precise assessment of GFR in small animals. As neither blood and/or urine sampling nor time-consuming lab work is required, GFR can be determined immediately after the clearance procedure is finished. This method, therefore, simplifies and fastens GFR determinations in small lab animals compared to conventional bolus clearance techniques based on blood sampling. A low-cost device for the measurement of transcutaneous fluorescence intensity over time is under construction.

• Dual-Energy CT Angiography in Peripheral Arterial Occlusive Disease.

  Authors: Carolin Brockmann, Susanne Jochum, Maliha Sadick, Kurt Huck, Peter Ziegler, Christian Fink, Stefan Schoenberg, Steffen Diehl

  Cardiovascular and interventional radiology. 02/2009;

  We sought to study the accuracy of dual-energy computed tomographic angiography (DE-CTA) for the assessment of symptomatic peripheral arterial occlusive disease of the lower extremity by using theWe sought to study the accuracy of dual-energy computed tomographic angiography (DE-CTA) for the assessment of symptomatic peripheral arterial occlusive disease of the lower extremity by using the dual-energy bone removal technique compared with a commercially available conventional bone removal tool. Twenty patients underwent selective digital subtraction angiography and DE-CTA of the pelvis and lower extremities. CTA data were postprocessed with two different applications: conventional bone removal and dual-energy bone removal. All data were reconstructed and evaluated as 3D maximum-intensity projections. Time requirements for reconstruction were documented. Sensitivity, specificity, accuracy, and concordance of DE-CTA regarding degree of stenosis and vessel wall calcification were calculated. A total of 359 vascular segments were analyzed. Compared with digital subtraction angiography, sensitivity, specificity, and accuracy, respectively, of CTA was 97.2%, 94.1%, and 94.7% by the dual-energy bone removal technique. The conventional bone removal tool delivered a sensitivity of 77.1%, a specificity of 70.7%, and an accuracy of 72.0%. Best results for both postprocessing methods were achieved in the vascular segments of the upper leg. In severely calcified segments, sensitivity, specificity, and accuracy stayed above 90% by the dual-energy bone removal technique, whereas the conventional bone removal technique showed a substantial decrease of sensitivity, specificity, and accuracy. DE-CTA is a feasible and accurate diagnostic method in the assessment of symptomatic peripheral arterial occlusive disease. Results obtained by DE-CTA are superior to the conventional bone removal technique and less dependent on vessel wall calcifications.

• Bias and precision of estimated glomerular filtration rate in children.

  Authors: Norbert Gretz, Daniel Schock, Maliha Sadick, Johannes Pill

  Pediatric nephrology (Berlin, Germany). 03/2007; 22(2):167-9.

  Determining true glomerular filtration rate (GFR) using an exogenous marker is time-consuming and cumbersome. Therefore, creatinine-based estimates of GFR are used. Recent papers using newDetermining true glomerular filtration rate (GFR) using an exogenous marker is time-consuming and cumbersome. Therefore, creatinine-based estimates of GFR are used. Recent papers using new population-specific/local parameters in their prediction equations, standardizing creatinine determination or adding other endogenous surrogate markers of GFR, like cystatin C, could demonstrate an improvement of bias inherent in the results of the prediction equations. Precision, however, is still poor. Currently, we have to accept a precision (as defined in the so-called Bland-Altman plot) of +/-20% in adults and +/-30-40% in children. This problem of poor precision/uncertainty is especially bothering in the higher, near normal GFR range. Caution should be exercised when applying prediction equations in individuals in need of an accurate GFR determination. In that case, a real clearance procedure has to be performed. In the long run, the true clearance procedure should be simplified using new exogenous GFR markers and developing new devices, allowing GFR measurements to be performed, for example, transcutaneously. Such a procedure would be more acceptable for both patients and physicians.

• Twenty-four-hour and annual variation in onset of epistaxis in Osler disease.

  Authors: Haneen Sadick, Inigo Fleischer, Ulrich Goessler, Karl Hörmann, Maliha Sadick

  Chronobiology international. 02/2007; 24(2):357-64.

  Osler disease is an autosomal dominant disorder of the fibrovascular tissue characterized by arteriovenous malformations with multi-systemic haemorrhages. Recurrent epistaxis is the predominantOsler disease is an autosomal dominant disorder of the fibrovascular tissue characterized by arteriovenous malformations with multi-systemic haemorrhages. Recurrent epistaxis is the predominant symptom in more than 90% of patients. Recent studies showed circadian and seasonal patterns in the onset of nosebleeds, similar to acute cardiovascular events, such as myocardial infarction and stroke. The aim of this study was to determine whether such patterns would also apply to the onset of epistaxis in patients with Osler disease. In all, 110 patients with Osler disease who were under treatment for recurrent epistaxis at the University Hospital of Mannheim were requested to complete a questionnaire addressing the intensity and frequency of epistaxis according to the classification of Bergler et al., as well as circadian and circannual rhythmicity in the occurrence of epistaxis according to visual analogue scales (VAS). More than half of the patients claimed to experience daily to weekly episodes of recurrent epistaxis. The occurrence of epistaxis showed a biphasic 24 h pattern, with a primary peak in the morning (05:00-8:00 h) and smaller secondary peaks in the evening (17:00-20:00 h and 21:00-00:00 h). No significant seasonal variation was found in the onset of epistaxis. However, a slight tendency, with a peak in winter months, was observed. Similar to other chronobiological studies on nosebleeds, this study showed that the 24 h pattern and seasonal tendency in the onset of epistaxis even applied to patients with Osler disease. Further investigations are necessary to determine the pathological mechanism underlying this phenomenon.

• Multislice CT-angiography in percutaneous postinterventional hematuria and kidney bleeding: Influence of diagnostic outcome on therapeutic patient management. Preliminary results.

  Authors: Maliha Sadick, Boris Röhrl, Peter Schnülle, Christoph Düber, Steffen J Diehl

  Archives of medical research. 02/2007; 38(1):126-32.

  BACKGROUND: The aims of this study were to assess the value of multislice CT-angiography (MS-CT-A) in percutaneous postinterventional kidney bleeding and to determine the influence of diagnosticBACKGROUND: The aims of this study were to assess the value of multislice CT-angiography (MS-CT-A) in percutaneous postinterventional kidney bleeding and to determine the influence of diagnostic outcome on therapeutic patient management. A recommendation for the interdisciplinary patient work-up for the emergency room was offered. METHODS: Between April 2003 and January 2006, 12 patients with hematuria and clinically suspected renal bleeding underwent MS-CT-A for emergency diagnostic assessment. The spectrum of kidney injuries on CT was analyzed according to an organ-scaling scheme. The efficacy of MS-CT-A with regard to confirmation of active arterial bleeding was evaluated as well as the therapeutic consequences for patient management. RESULTS: In seven patients (59%) staged grade V renal injury, active renal arterial bleeding was detected on CT-A. Patients immediately underwent therapeutic angiography with confirmation of arterial bleeding and successful embolization. Four patients (33%) were staged grade I renal injury with subcapsular kidney hematoma but no active hemorrhage. Therefore, these patients were not exposed to further therapeutic intervention. One patient (8%) was diagnosed grade II renal injury with superficial cortical renal parenchyma tear and no active bleeding on CT-A. CONCLUSIONS: MS-CT-A is a valuable, fast and objective emergency tool for assessment of postinterventional renal hemorrhage. Detection of contrast material extravasation to affirm ongoing arterial bleeding and to localize bleeding site at the level of segmental or interlobar renal artery is a predictor for the need for further treatment and justifies therapeutic radiological or surgical management.

• Pharmacological profile and toxicity of fluorescein-labelled sinistrin, a novel marker for GFR measurements.

  Authors: Johannes Pill, Oxana Issaeva, Stefanie Woderer, Maliha Sadick, Bettina Kränzlin, Fritz Fiedler, Hans-Martin Klötzer, Uwe Krämer, Norbert Gretz

  Naunyn-Schmiedeberg's archives of pharmacology. 07/2006; 373(3):204-11.

  There is an evident and growing medical need for an accurate determination of kidney function for a broad spectrum of indications. The glomerular filtration rate (GFR) is the most accepted indicatorThere is an evident and growing medical need for an accurate determination of kidney function for a broad spectrum of indications. The glomerular filtration rate (GFR) is the most accepted indicator of renal function. Due to difficulties in performing the test, GFR is currently determined rarely in clinical practice. A procedure for such GFR determination has to be safe, accurate and easy to handle. By using the new compound fluorescein isothiocyanate-sinistrin (FS) these requirements are met. The pharmacological profile and tolerability of FS, selected from among various newly synthesized, labelled compounds intended for use as GFR markers, was characterized in male Sprague-Dawley rats following i.v. application. Using the newly described fluorometric method, FS can be determined much more easily in serum and urine than with the established enzymatic method. After i.v. dosing, FS concentrations in serum declined rapidly in various experimental groups to a comparable extent (t (1/2), mean+/-SD: 22.4+/-8.3 to 26.2+/-5.4 min). Its increase after unilateral nephrectomy reflects the loss of filtration capacity. Comparable concentration-time curves of FS in serum measured fluorometrically and enzymatically suggest no relevant alteration of pharmacokinetic behaviour by the labelling. This notion is supported by the high urinary excretion rate and absence of biliary excretion. The higher sensitivity of the fluorometric method suggests a dose of FS of 100 mg in humans compared with 5 g of sinistrin or inulin. FS was well tolerated after single and multiple applications. On the basis of these results, the kinetics of FS are comparable with the gold standard inulin or sinistrin, but FS is superior in handling. Providing the data can be transferred from rat to human, determination of GFR using the new method should result in an improvement of acceptance by both physicians and patients.

• Hereditary hemorrhagic telangiectasia: an update on clinical manifestations and diagnostic measures.

  Authors: Haneen Sadick, Maliha Sadick, Karl Götte, Ramin Naim, Frank Riedel, Gregor Bran, Karl Hörmann

  Wiener klinische Wochenschrift. 04/2006; 118(3-4):72-80.

  Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is an autosomal dominant disorder of the fibrovascular tissue. It is characterized by the classic triad ofHereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is an autosomal dominant disorder of the fibrovascular tissue. It is characterized by the classic triad of (muco-)cutaneous telangiectases, arteriovenous malformations with recurrent epistaxis and hemorrhages, and inheritance. A wide variety of clinical manifestations in HHT have been described. In more than 90% of the patients, nosebleeds are the first predominant symptom, therefore ENT physicians often play a key role as far as diagnosis and management of the disease are concerned. In spite of recent diagnostic and therapeutic progress, a cure for this often burdening and handicapping disease is still not available. Apart from affecting the nose, arteriovenous malformations (AVMs) may also affect the skin, lungs, brain, liver and gastrointestinal tract. The two known genes that are implicated in HHT are endoglin (ENG) located on chromosome 9q33-q34 and activin-receptor-like kinase (ALK1) located on chromosome 12q13. Mutations of ENG are observed in HHT type 1 with an incidence up to 40% for pulmonary AVMs, whereas mutations of ALK1 are observed in HHT type 2 with an incidence of only 14% for pulmonary AVMs, which clinically distinguishes these two types of mutation. The emphasis of this paper is mainly on the clinical manifestation, molecular genetics and diagnosis of HHT, taking account of current literature on HHT in order to better understand the complexity of the disease. Recent therapeutic options in the treatment of HHT have been omitted from this paper as they are subject of a following paper. HHT is more common than previously thought and shows a broad range of different clinical organ manifestations that can be sources of substantial morbidity and mortality, making HHT a continuing challenge for many sub-specialties where interdisciplinary diagnostic screening is mandatory in the management of the disease.

• Cross-sectional imaging combined with 3D-MR angiography (3D-MRA): diagnostic tool for preoperative vascular assessment of head and neck tumors.

  Authors: Maliha Sadick, Haneen Sadick, Karl Hörmann, Christoph Düber, Steffen J Diehl

  Onkologie. 11/2005; 28(10):477-81.

  BACKGROUND: Head and neck cancer accounts for 5% of all malignancies worldwide. The presence of lymph node metastases and vascular infiltration influence patient outcome. This prospective studyBACKGROUND: Head and neck cancer accounts for 5% of all malignancies worldwide. The presence of lymph node metastases and vascular infiltration influence patient outcome. This prospective study describes the preoperative morphologic assessment of the vascular status of patients with head and neck tumors by means of high spatial resolution and extended coverage of the arterial and venous system reaching from the supra-aortic region to the skull base. PATIENTS AND METHODS: Cross-sectional imaging combined with contrast-enhanced 3D-maximum intensity projection MR angiography (3D-MRA) was applied using a dedicated head and neck coil with a 4-channel panorama array system interface to assess vascular involvement in patients with suspected head and neck cancer. 32 patients underwent preoperative assessment by magnetic resonance imaging (MRI). The results were then correlated with surgical and histological findings. RESULTS: 3 of the 32 patients (9%) demonstrated involvement of the arterial system. In 2 of these 3 cases, MRA correctly predicted the arterial status, while in 1 case it gave a false negative result. 11 of the 32 patients (34%) presented with involvement of the venous system. 10 cases showed complete concordance between the findings of the MR venography and the intraoperative status, while in 1 case a false negative result was produced. CONCLUSION: In patients with suspected head and neck tumors, 3D-MRA in combination with cross sectional imaging is a valuable diagnostic tool for the detection of vascular involvement.

• Fluorescein-labeled sinistrin as marker of glomerular filtration rate.

  Authors: Johannes Pill, Bettina Kraenzlin, Julia Jander, Tim Sattelkau, Maliha Sadick, Hans-Martin Kloetzer, Carsten Deus, Uwe Kraemer, Norbert Gretz

  European journal of medicinal chemistry. 11/2005; 40(10):1056-61.

  There is an obvious and growing medical need for an accurate and easy to handle determination of glomerular filtration rate (GFR) for a broad spectrum of indications. Newly synthesizedThere is an obvious and growing medical need for an accurate and easy to handle determination of glomerular filtration rate (GFR) for a broad spectrum of indications. Newly synthesized fluorescein-isothiocyanate (FITC)-sinistrin (FS) with various degrees of labeling was selected by its physicochemical properties and good tolerability out of a number of dye-labeled compounds intended for use as GFR markers for characterization of its pharmacological profile. With respect to solubility FS is more convenient in handling compared to FITC-inulin (FI). Up to 100 mg ml(-1) of FS can be dissolved in aqueous solvents at room temperature, whereas FI can only be solubilized after warming up to 55 degrees C. This reveals a considerable advantage of FS over FI in preparation of galenical formulations for intended i.v. application. A fluorometric method was established to determine FS concentration in blood serum with a comparable accuracy to the established enzymatic method for polyfructosanes. Similar concentration time curves in blood serum of FS measured fluorometrically and enzymatically suggest no relevant change of pharmacokinetic behavior by dye labeling. This notion is supported by the rapid renal and missing of biliary excretion. On the basis of these results, FS is superior in handling to the available GFR markers and makes it highly interesting as a novel diagnostic drug.

• Diagnostic evaluation of magnetic resonance imaging with turbo inversion recovery sequence in head and neck tumors.

  Authors: Maliha Sadick, Haneen Sadick, Karl Hörmann, C Düber, Steffen J Diehl

  European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 09/2005; 262(8):634-9.

  The clinical outcome of patients with head and neck cancer depends on many factors such as tumor size, metastatic involvement and angioarchitecture of the tumor. The correct staging of tumorThe clinical outcome of patients with head and neck cancer depends on many factors such as tumor size, metastatic involvement and angioarchitecture of the tumor. The correct staging of tumor extension, presence of cervical lymph node metastases and evaluation of vascular infiltration are essential diagnostic steps before treatment. The aim of this study was to evaluate the accuracy of turbo inversion recovery magnitude (TIRM) magnetic resonance imaging (MRI) in the diagnosis of head and neck tumors with special attention to tumor size and tumor spread according to the current TNM classification. TIRM sequence with short T1 relaxation and long TE (echo time) improves imaging contrast because of the increased T1-weighting and the inherent fat suppression. In a prospective clinical study, 32 patients underwent preoperative MRI. Diagnosis was confirmed histologically in all cases. Scanning was performed on a 1.0-T unit applying TIRM as well as T1- and T2-weighted turbo spin echo (TSE) sequences. In all sequences, tumor size was overestimated due to reactive inflammatory changes surrounding the tumor tissue. The least overestimation was documented on TIRM and post-contrast T1 TSE. The highest values of relative tumor signal intensities were obtained in TIRM (3.5+/-0.9) and T2 TSE (3.5+/-0.8) followed by post-contrast T1 TSE (1.6+/-0.7) and pre-contrast T1 TSE (1.2+/-0.3). Due to the inherent fat suppression, tumor delineation was most obvious in TIRM. In patients with suspected cancer of the head and neck, TIRM should be considered as a standard and a diagnostically relevant sequence in the MRI staging protocol.

• Direct fluorometric analysis of a newly synthesised fluorescein-labelled marker for glomerular filtration rate.

  Authors: Johannes Pill, Hans-Martin Kloetzer, Oxana Issaeva, Bettina Kraenzlin, Carsten Deus, Uwe Kraemer, Maliha Sadick, Fritz Fiedler, Norbert Gretz

  Analytical and bioanalytical chemistry. 06/2005; 382(1):59-64.

  There is an obvious and growing medical need for an accurate determination of kidney function in the diagnosis and management of renal diseases. The glomerular filtration rate (GFR) is the acceptedThere is an obvious and growing medical need for an accurate determination of kidney function in the diagnosis and management of renal diseases. The glomerular filtration rate (GFR) is the accepted gold standard measurement of kidney function. Several approaches to estimate the GFR are available, but most of them are inconvenient and, therefore, of limited acceptance. A new method of quantification with fluorescein-isothiocyanate (FITC) sinistrin (FS), a novel GFR marker, has been evaluated. The method is based on the fluorescence label of FS and can be performed with a standard fluorometer. To control the interference of protein with the fluorescence signal, a calibration function was developed. The accuracy of the fluorometric method established is comparable to the so-called "gold standard" of enzymatic determination of polyfructosan. Moreover, FS is easy to handle and requires low-cost instruments. Our results demonstrate the potential of the direct fluorometric analysis of the new FITC-labelled marker of being a precise, simple, rapid and cost-effective method for diagnosing disturbed kidney function and monitoring its treatment efficacy. The dramatic decrease in analytical effort will result in a significantly higher acceptability of GFR determination.

• Plasma level and tissue expression of angiogenic factors in patients with hereditary hemorrhagic telangiectasia.

  Authors: Haneen Sadick, Ramin Naim, Maliha Sadick, Karl Hörmann, Frank Riedel

  International journal of molecular medicine. 05/2005; 15(4):591-6.

  The value of angiogenic factors interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) was determined in patients with hereditary hemorrhagic telangiectasia (HHT) to evaluate their roleThe value of angiogenic factors interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) was determined in patients with hereditary hemorrhagic telangiectasia (HHT) to evaluate their role in HHT pathogenesis. IL-8 and VEGF were measured in plasma of 41 HHT patients and healthy controls by ELISA technique. In both groups, the IL-8 and VEGF tissue expression in cryostat sections of the nasal mucosa were then compared. VEGF plasma levels were significantly increased in HHT patients compared to healthy controls. In contrast, the IL-8 plasma levels in both groups did not show any significant difference. Compared to healthy controls, HHT tissue samples showed a weak IL-8 staining, whereas the VEGF staining was very strong. The plasma levels of VEGF and IL-8 could not be correlated to the patients' clinicopathological findings. Additionally to the angiogenic pro-inflammatory cytokine IL-8, the angiogenic factor VEGF seems to play a major role in HHT pathogenesis.

• [Is imaging possible for otosclerosis? Characteristics of the disease and a survey of the clinical relevance of imaging]

  Authors: Haneen Sadick, Maliha Sadick, Karl Hörmann

  Wiener medizinische Wochenschrift (1946). 04/2005; 155(5-6):118-23.

  Otosclerosis is a localized progressive disease of bone remodeling within the otic capsule of the human temporal bone. Histomorphologically, active cochlea otosclerosis (otospongiosis) is diagnosedOtosclerosis is a localized progressive disease of bone remodeling within the otic capsule of the human temporal bone. Histomorphologically, active cochlea otosclerosis (otospongiosis) is diagnosed in the presence of foci of demineralization in the otic capsule. The clinical symptoms of otosclerosis are associated with mixed and sensorineural hearing loss. With recent technological advances, diagnostic imaging of the inner ear is becoming more and more important in the evaluation of diseases affecting the cochlea. Studies could demonstrate that otosclerosis has a characteristic appearance on high-resolution computed tomography (HRCT), producing a distinctive pericochlear hypodense double ring. Its appearance on MRI is not as readily appreciated, producing a ring of intermediate signals in the pericochlear and perilabyrinthine regions on T1-weighted images, demonstrating mild to moderate enhancement after gadolinium administration. The ethiology and pathophysiology of otosclerosis are described and a review of the literature is given to illustrate the clinical relevance of imaging in otosclerosis.

• Estriol induced squamous metaplasia on the nasal mucosa in patients with hereditary hemorrhagic telangiectasia.

  Authors: Haneen Sadick, Wolfgang F Bergler, Jasmina Oulmi-Kagermann, Ramin Naim, Maliha Sadick, Karl Hörmann, Frank Riedel

  Archives of medical research. 36(5):468-73.

  BACKGROUND: The aim of this study was to evaluate by light and electron microscopy the effect of topical estriol on the nasal mucosa in patients with hereditary hemorrhagic telangiectasia (HHT).BACKGROUND: The aim of this study was to evaluate by light and electron microscopy the effect of topical estriol on the nasal mucosa in patients with hereditary hemorrhagic telangiectasia (HHT). METHODS: Twelve patients were instructed to apply twice daily 0.1% estriol as a nose ointment over a period of 12 months. Written consent was obtained from each patient, allowing biopsy specimens of the nasal mucosa to be taken prior to and 3, 6 and 12 months after estriol application. RESULTS: Metaplastic change of the nasal mucosa was observed 6 months after topical estriol application. The former ciliated columnar epithelium changed into a keratinizing squamous epithelium. The effect was reversible after discontinuation of estriol application. CONCLUSIONS: For the first time, we could outline the effect of topical estriol on the nasal mucosa. These histomorphological findings, and the fact that estriol is a low-potency metabolite of estradiol, make estriol a valuable agent in the treatment of HHT patients.