The novel gene MIA2 acts as a tumour suppressor in hepatocellular carcinoma.

BACKGROUND: Melanoma inhibitory activity 2 (MIA2) is a novel gene of the MIA gene family. The selective expression of MIA2 in hepatocytes is controlled by hepatocyte nuclear factor (HNF) 1 binding sites in the MIA2 promotor. In contrast, in most hepatocellular carcinomas (HCC) MIA2 expression is down-regulated or lost. AIM: In this study we examined the regulation and functional role of MIA2 in hepatocancerogenesis. METHODS AND RESULTS: In HCC cell lines and tissues HNF-1 expression was lower than in primary human hepatocytes (PHH) and corresponding non-tumorous tissue, respectively, and correlated significantly with the down-regulation of MIA2 expression. Re-expression of HNF-1 in HCC cells reinduced MIA2 in HCC cells to similar levels as found in PHH. Further, MIA2 was re-expressed in HCC cell lines by stable transfection, and the generated cell clones revealed a strongly reduced invasive potential and proliferation rate in vitro. In line with these findings treatment of HCC cells with recombinant MIA2 inhibited proliferation and invasion. In nude mice MIA2 re-expressing HCC cells grew significantly slower and revealed a less invasive growth pattern. Immunohistochemical analysis of a tissue microarray containing HCC and corresponding non-cancerous liver tissue of 85 patients confirmed reduced MIA2 expression in HCC. Furthermore, MIA2 negative HCC tissue showed a significantly higher Ki67 labelling index and loss of MIA2 expression correlated significantly with more advanced tumour stages. CONCLUSION: This study presents MIA2 as an inhibitor of HCC growth and invasion both in vitro and in vivo, and consequently, as a tumour suppressor of HCC. Further, our findings indicate a novel mechanism, how loss of HNF-1 expression in HCC affects tumorigenicity via down-regulation of MIA2.

The value of intraoperative angiography in surgery of intracranial aneurysms: a prospective study in 126 patients.

The value of intraoperative digital subtraction angiography in surgery for intracranial aneurysms, the benefits and cost-effectiveness are a matter of discussion. We prospectively studied 126 patients with 144 aneurysms, most on the anterior intracranial circulation, who underwent clipping and intraoperative angiography. Follow-up was 28.4 +/- 13.1 months. We tried to work out the indications for intraoperative angiography of the anterior circulation and its cost-effectiveness. In 10.3 % of patients (9 % per aneurysm) unexpected findings were shown by intraoperative angiography: inadequately clipped aneurysms in 10 (7.9 %), a completely unclipped aneurysm in one (0.8 %) and occluded major arteries in two (1.6 %). A broad neck was a variable of statistical significance for inadequate clipping or stenosis or occlusion of an adjacent vessel. There was a strong trend for aneurysms more than 15 mm in diameter to be "risky". Their site was not a predictive factor. We believe that intraoperative angiography is indicated in surgery not only on large and giant aneurysms, but also broad-based aneurysms of the anterior cerebral circulation regardless of their size. It is cost-effective compared to postoperative angiography. The rate of stroke in our hands was 0.8%.

Chest ultrasound in diagnosis of pulmonary embolism in comparison to helical CT.

UNLABELLED: To many people die because of undiagnosed pulmonary embolism. Common pulmonary embolism is the most unexpected mortal event in necropsy, antemortem correctly diagnosed in 18-39%. The diagnostic value of chest ultrasound (CUS) has been investigated. METHODS: 117 (68 women, 49 men) patients with clinical suspicion of pulmonary embolism underwent chest sonography and spiral computed tomography (CT). Final diagnosis has been made by CT respective with echo-cardiography, venous duplex sonography and fibrin dimer tests. RESULTS: Finally, 70 patients suffered from pulmonary embolism. The chest sonograms showed averaged 1.5 x 2.8 cm (0.5-8.5) large triangular or rounded hypoechoic lesions, mean 2.6 pro patient, similar in form and size as in CT. Fresh reperfusionable infarcts were homogenous and hypoechoic. Older infarcts were well demarcated, mainly wedge shaped. A hyperechoic reflex in the center corresponds to the bronchiole: a sign of segmental involvement. The sensitivity of chest ultrasound was 94%, the specificity 87%, positive predictive value 92%, negative predictive value 91%, accuracy 91%. Overall 61 patients had PE in CT, in 47 (67%) cases a direct emboli detection was possible. 14 patients had peripheral lung consolidations without detectable emboli, but fibrin-dimer tests were positive in all cases, there was deep vein thrombosis diagnosed and they showed signs of PE in echocardiography. Spiral CT showed a sensitivity of 85%, a specificity and a positive predictive value of 100%, a negative predictive value of 83% and an accuracy of 92%. CONCLUSION: CUS can improve diagnosis of pulmonary embolism. Sonography also reveals small infarcts which remain undetected with other imaging procedure such as helical CT.

[Laser-tyndallometry in eyes with acute retinal necrosis syndrome. Erlanger Laser-tyndallometry study group]. / Laser-Tyndallometrie bei Augen mit akutem retinalen Nekrosesyndrom. Erlanger Arbeitsgruppe "Laser-Tyndallometrie.

PURPOSE: Acute retinal necrosis syndrome (ARN) is a rapidly progressive viral necrotic retinitis. We used noninvasive measurement of aqueous flare to quantify blood-ocular barrier breakdown in eyes with ARN und to follow the inflammatory activity and treatment effects. PATIENTS AND METHODS: We report on seven patients (5 males und 2 females, age: 16 to 57 years) with ARN that were treated in our institution between 1991 to 1996. Aqueous flare was quantified regularly during treatment using the laser flare-cell meter (Kowa, FC-1000) following pupillary dilation. RESULTS: Aqueous flare was highly significantly increased in eyes with ARN (145.5 +/- 139.7, range 30 to 367 photon counts/ms). Contralateral, unaffected eyes showed normal flare values (3.6 +/- 0.8 photon counts/ms, p < 0.0001; normals: 4.1 +/- 1.1 photon counts/ms). Flare values correlated with inflammatory activity before and during antiviral treatment. In two patients with ARN caused by herpes simplex-virus aqueous flare values were extremely increased (367 and 316 photon counts/ms), and retinal necrosis was rapidly progressive despite antiviral therapy. One patient developed early ARN in his contralateral eye with flare values increasing from 3.5 to 22.0 photon counts/ms, which quickly normalized following antiviral treatment. CONCLUSIONS: Measurement with the laser flare-cell meter allows quantification of blood-ocular barrier breakdown in eyes with ARN und may be useful for monitoring inflammatory activity during treatment.

Stromal thermal effects induced by nonmechanical (2.94-mum) erbium:YAG laser corneal trephination.

OBJECTIVE: To determine stromal thermal changes after erbium (Er):YAG laser corneal trephination with the use of 2 open masks. METHODS: Corneal trephination was performed in 89 enucleated pig eyes with an Er:YAG laser (400-microsecond pulse duration), 4 open masks (2 metallic and 2 ceramic) for both donors and recipients, and an automated globe rotation device. Different combinations of laser settings were used: pulse energy, 100, 200, and 400 mJ; repetition rate, 2 and 5 Hz; and spot size, 1.3 and 3.2 mm. Thermal effects in corneal stroma and regularity of the cut edges were quantitatively assessed by light microscopy, transmission and scanning electron microscopy. RESULTS: Best regularity and minimal thermal effects of the cut were observed with the use of ceramic masks at 200 mJ, 2 Hz, and 3.2-mm spot size, with middepth thermal changes of 18 +/- 2 microm. Effects increased with cut depth and were lower in donor corneas and with the use of ceramic masks (P<.001). Regularity of the cut was higher in the donors (P = .05) with lower repetition rates (P<.001). CONCLUSIONS: Even with the "free-running" Er:YAG laser mode, features of the trephination cut resembling those created by the 193-nm excimer laser along metal mask were achieved. Ceramic masks may be more suitable than metal masks. The Er:YAG laser seems to have the potential to be a compact and low-cost alternative in nonmechanical trephination for penetrating keratoplasty. CLINICAL RELEVANCE: Thermal effects after corneal trephination with the free-running Er:YAG laser (2.94 mm) are limited and predictable.

[Tyndallometry and cell count in the anterior chamber in retinal detachment]. / Tyndallometrie und Zellzahlmessung in der Vorderkammer bei Amotio retinae.

BACKGROUND: Aim of this study was the investigation of changes of aqueous flare and cells in eyes with retinal detachment. PATIENTS AND METHODS: We examined 62 eyes of 61 patients with retinal detachment (56 eyes with rhegmatogenous retinal detachment, 6 eyes with traction retinal detachment; 51 eyes without and 11 eyes with clinical signs of proliferative vitreoretinopathy (PVR) stage C) with the laser flare-cell meter (LFCM) and compared the results with clinical findings and with the results of a control group. RESULTS: The flare values as well as the cell count of all eyes with retinal detachment were significantly elevated (p < 0.0001) in comparison to those of the control group. In eyes with PVR a significant elevation of flare values in comparison to eyes without PVR appeared (p = 0.0052). A slight correlation was found between the extension of the detachment and the flare values and the cell count, respectively. In cases with rhegmatogenous retinal detachment a significant elevation of the cell count was found if the largest break was localized in the upper hemisphere (p = 0.03) or if the macula was affected (p = 0.02). In rhegmatogenous retinal detachment, the cell count correlated slightly with the age of the patients (r = 0.3, p = 0.02), and flare values correlated with the height of the detachment (r = 0.28, p = 0.04). CONCLUSIONS: Our results demonstrate a breakdown of the blood-ocular barriers in eyes with retinal detachment and an elevation of corpuscular elements in aqueous as manifestations of pseudouveitis. In eyes with PVR the alteration of blood-ocular barriers seems to be more extensive than in eyes without PVR indicating a possible role of the LFCM for early detection of PVR.

A second independent Tyr168Cys mutation in the tissue inhibitor of metalloproteinases-3 (TIMP3) in Sorsby's fundus dystrophy.

Sorsby's fundus dystrophy (SFD) is a rare autosomal dominant macular disorder with age of onset usually in the fourth decade. It is characterised by loss of central vision owing to subretinal neovascularisation and disciform macular degeneration. In an effort to identify the SFD gene, the disease locus was first mapped to chromosome 22q13-qter by genetic linkage analysis, the same chromosomal region as the gene encoding the tissue inhibitor of metalloproteinases-3 (TIMP3). Subsequently, two separate mutations in TIMP3 were found in affected members of two unrelated SFD pedigrees (Tyr168Cys and Ser181Cys). More recently, two additional SFD related mutations, Ser156Cys and Gly167Cys, have provided further confirmation that heterozygous mutations in TIMP3 are causally responsible for the SFD phenotype. We now report the occurrence of the Tyr168Cys mutation in an SFD patient of Austrian descent and show that this mutation found earlier in an American SFD family arose independently. The new findings add to an emerging pattern of SFD mutations which all seem to affect the C-terminal region of the mature TIMP3 protein. In addition, all known mutations cause a change of an amino acid to a cysteine residue. This suggests a critical role for the additional C-terminal free thiol group in SFD pathogenesis.

MR-myelography: a comparison with conventional myelography.

After creating a MR pulse sequence, called MR-myelography, the purpose of the study was to evaluate the value of this sequence in comparison to conventional myelography. Twenty consecutive patients were examined with conventional and MR-myelography concerning the clinical questions of chronic lumbago, spinal canal stenosis, herniated disc, spondylolisthesis and instability. Six observers assessed both examinations independently for subjective criteria such as pictorial quality, depiction of the dural sac, the nerve roots and their sheaths, artifacts, and the usefulness of single MR-myelography slices. Furthermore the number and extent of stenoses had to be judged as an objective criteria. The employed MR-myelography technique is not able to concur with the quality of conventional myelography. A high-grade stenosis is usually overestimated and low grade stenosis underestimated by MR-myelography. But it is easier to depict further relevant stenoses in a preexisting high grade stenotic spinal canal with MR-myelography. Artifacts of the introduced MR-technique do not disturb pictorial and diagnostic quality very much. In conclusion MR-myelography cannot replace conventional myelography. But together with conventional MR-sequences, MR-myelography can be helpful in the assessment of spinal canal stenosis.

[Ultrasound pathology of the axilla. Part II]. / Sonopathologie der Axilla. II. Teil.

In comparison with other diagnostic modalities axillary sonography undoubtedly is highly valuable examining unclear palpation findings, in the staging of tumours with lymphatic drainage to the axilla and in posttherapeutic screening of cancer patients. Usually pathologic changes of the axilla are due to diseases of the lymph nodes. Infrequently there are soft tissue tumours, inflammations, diffuse changes of the axillary soft tissue, vascular diseases and pathologic findings of the shoulder joint. Provided the most common sonographic features of morphologic changes of the axillary tissues are known, sonography of the axilla is a very important diagnostic tool and is extremely helpful in deciding on further diagnostic and therapeutic procedures. Part I deals with the pathology of the axillary lymph nodes, whereas in part II pathological changes of the other soft tissues are discussed in detail.

[Sonographic pathology of the axilla. Part I]. / Sonopathologie der Axilla. I. Teil.

In comparison with other diagnostic modalities axillary sonography undoubtedly is highly valuable in when examining unclear palpation findings, in the staging of tumours with lymphatic drainage to the axilla and in post-therapeutic screening of cancer patients. Usually pathologic changes of the axilla are due to diseases of the lymph nodes. Infrequently there are soft tissue tumours, inflammations, diffuse changes of the axillary soft tissue, vascular diseases and pathologic findings of the shoulder joint. Provided the most common sonographic features of morphologic changes of the axillary tissues are known, sonography of the axilla is a very important diagnostic tool and is extremely helpful in deciding on further diagnostic and therapeutic procedures. Part I deals with the pathology of the axillary lymph nodes, whereas in part II pathological changes of the other soft tissues are discussed in detail.

[Sonographic anatomy of the axilla]. / Sonoanatomie der Axilla.

The axilla represents a region of special interest for small-part sonography. It is easy to demonstrate musculocutaneous, osseous, neurovascular and lymphatic structures. Especially in the presence of breast malignomas with lymphatic drainage to the axillary region sonography of the axillary lymphatic tracts and nodes is essential. The examination is performed with a linear 7.5 MHz transducer with the patient in supine position and the arm hyperabducted. The transducer is directed in transversal and sagittal planes and along the axillary vessels. It is of importance to know exactly the complex topographic anatomy of the axilla. The very dominant pectoral muscles serve as guiding structures. In their vicinity one can find some important groups of lymph nodes. The last station of axillary lymph nodes is the apical group situated along the axillary neurovascular bundle. With their typical echo, the head of the humerus and the coracoid-process facilitate the orientation. Ultrasound is now generally available and should always be used as a secondary method of examination, it breast malignomas are present or suspected in mammogramms, since it supplies important clinical information.

[Experiences with a new breast localization needle]. / Erfahrungen mit einer neuen Mammalokalisationsnadel.

In view of the increasing number of biopsies of non-palpable lesions of the female breast we found an ideal localisation system in the Hawkins breast localisation needle. Localisation was successful without technical problems in 31 out of 34 patients. The special advantages of the needle are its stability in position and excellent maneuverability due to the construction of the needle. The very simple handling of the needle is an advantage not only for the radiologist but also for the surgeon.

[Hemobilia with spontaneous resolution. Sonographic diagnosis and follow-up]. / Hemobilia con resolución espontánea. Diagnóstico y evolución con ecografía.

We describe a case of hemobilia after liver biopsy, which resolved spontaneously. Clinical, analytical and sonographic monitoring were performed until the patient returned to normal. We highlight the particular characteristics of the onset and evolution in our case, as well as the role played by ultrasonography in diagnosing and monitoring. We conclude by pointing out the increasing frequency of hemobilia as a complication to invasive techniques.