Differential viral kinetics in treated genotype 4 chronic hepatitis C patients according to ethnicity.

Data concerning the efficacy of PEG-IFN alpha 2a plus ribavirin treatment in treatment-naive, genotype 4-infected chronic hepatitis C (CHC) patients from Europe are limited. Hence the aim of this study was to investigate the viral kinetics as well as the sustained virological response (SVR) rates and their predictors, in these patients. One hundred and twenty-three patients were retrospectively analysed. Early (EVR) and late virological response (LVR) was confirmed by undetectable (<50 IU/mL) serum HCV-RNA at week 12 and week 24 of treatment, respectively. SVR was confirmed by undetectable serum HCV-RNA at the end of treatment as well as 6 months later. Overall, 43.5% of patients exhibited SVR, 42.6% were nonresponders and 13.9% were relapsers. EVR was observed in 40.74% and LVR in 59.25% of them. The positive predictive values of EVR and LVR were 72.97% and 86.27% whereas their negative predictive values were 64.29% and 92.85%, respectively. EVR independently predicted SVR in Caucasian patients (P < 0.001) but not in Egyptian patients (P = 0.613), in whom the only independent predictor of SVR was the absence of cirrhosis (P = 0.004). LVR seems to be a better predictor of SVR than EVR in the vast majority of genotype 4-infected CHC patients, irrespective of ethnicity and all the other baseline parameters.

Growth of trigeminal neurites and interactions with corneal cells in embryonic chick organ cultures.

The investigation of interactions between growing neurites and target cells during the development of the sensible corneal innervation is of crucial importance for understanding certain corneal diseases which are related to abnormal patterns of innervation. The purpose of the present work was to establish a culture system of cornea and trigeminal neurons and to examine interactions between these tissues. The responses of neurons derived from explanted embryonic chick trigeminal ganglia to co-explanted slices prepared from embryonic cornea were monitored over several days in culture. The growth of trigeminal fibers, but not of neurites derived from control tissues such as trigeminal mesencephalic nucleus or ciliary ganglion, was preferentially directed towards the co-cultured corneal slices. The ingrowth of trigeminal axons into the cornea was followed by formation of elaborate axonal terminal branches. Individual dissociated trigeminal neurons of pseudo-unipolar or bipolar classes developed their typical morphologies in culture. In co-cultures with corneal slices, they reacted to the corneal co-explant by frequently retracting some branches and forming or elongating other ones, which were predominantly directed towards the target tissue. In addition, the presence of a co-explanted trigeminal ganglion increased the rate of growth in the dissociated trigeminal neurons. The effect was not additive when cornea was present. Antibodies against nerve growth factor (NGF) and the low-affinity p75-NGF receptor (LANGFR) revealed that trigeminal ganglion cells support neuritic growth by secreting NGF, whereas corneal cells secrete additional factor(s) which act via the LANGFR.

Successful management of para-aortic lymphocyst with laparoscopic fenestration.

Para-aortic lymphocyst occasionally follows retroperitoneal para-aortic node dissection for neoplastic diseases. We present a case in which the leakage of chylous fluid and then a para-aortic lymphocyst followed right nephrectomy and para-aortic node dissection for kidney cancer. Our method of treatment utilized conservative management of chylous ascites and laparoscopic internal drainage of the retroperitoneal lymphocyst.

An atypical presentation of upper urothelial tumor.

In some cases of primary transitional cell carcinoma (TCC), there may be some uncertainty in clinical decision making. We present a case in which a pT1-N0 urothelial tumor was found in the renal pelvis after an open nephrectomy for urolithiasis. Because incomplete excision of the ureter can lead to recurrence of the TCC, we deemed it necessary to remove the residual ureter. Therefore, a combined endoscopic-transvescical laparoscopic ureterectomy was performed. The transabdominal approach was chosen for the procedure, because the patient had already undergone open nephrectomy with retroperitoneal access and was thus likely to have adhesions and inflammation in the region. For the endoscopic phase of surgery, a technique of ureteral intussusception was combined with transurethral resection. The choice of the endoscopic transurethral procedure was prompted by the fact that transurethral resection of the ureteral orifice and invagination ureterectomy has already been proposed as the first step of nephroureterectomy. The combined endoscopic laparoscopic procedure was not technically demanding; the ureterectomy took no longer than an open procedure. The surgery was uneventful, and the patient resumed normal activities the day after surgery. The broader issue of whether this technique should be adopted by the urological community at large as a routine practice requires longer follow-up outcome data.

[High field MR imaging: magnetic field interactions of aneurysm clips, coronary artery stents and iliac artery stents with a 3.0 Tesla MR system]. / Hochfeld-Magnetresonanztomographie: Magnetische Anziehungs- und Rotationskräfte auf metallische Implantate bei 3.0 T.

PURPOSE: To evaluate magnetic field interactions of commonly used biomedical implants at 3.0 Tesla. MATERIALS AND METHODS: Fourteen aneurysm clips designed for permanent placement in intracranial aneurysms, 19 coronary artery stents and 20 iliac artery stents were evaluated in an actively shielded compact 3.0 T MR system (Intera, Philips Medical Systems, Best, The Netherlands, length of magnet 1.57 m). The magnetic deflection forces (translational movement) were evaluated as follows: The implants were suspended by a fine string and placed in the magnet bore at the location of the maximum magnetic field gradient. The translational forces F (z) were calculated from the measured angle of deflection from the vertical axis. The magnetic field-induced torque (rotational forces) was evaluated as follows: Each implant was placed in the center of the magnetic bore parallel to the static magnetic field B0 (position 0 degrees ). Any possible displacement of the implant was noted on a millimeter scale and any torque qualitatively evaluated using a 5 point grading scale (0: no torque; + 4: very strong torque). The implant was turned in steps of 45 degrees, and the procedure was repeated to encompass a full 360 degrees rotation. RESULTS: In 52 of the 53 devices tested, the deflection force (deflection angle: range 0-21 degrees, translational force: range 0-3.8 mN) was less than the gravitational force (i.e., the implant's weight). These devices (n = 52/53) did not show any alignment to or rotation in the magnetic field at any of the various 45 degrees -increment positions corresponding to a qualitative torque evaluation of grade 0/4. One device (n = 1/53), an iliac artery stent made of stainless steel (Zenith, Cook, Mönchengladbach, BRD), was found to have deflection forces (deflection angle 88 degrees translational force 299 mN) greatly exceeding the gravitational force as well as a pronounced torque (grade 4/4). CONCLUSION: Out of 53 biomedical implants evaluated for magnetic field interactions at 3.0 T, one iliac artery stent made of stainless steel was found to be potentially unsafe based on ASTM criteria. MR imaging at 3.0 Tesla may be performed safely in patients with any of the other 52 different implants evaluated in this study with respect to magnetic field translational attraction and torque.

[Immunohistologic, ultrastructural and morphometric characterization of organ cultures of the human limbus epithelium]. / Immunhistologische, ultrastrukturelle und morphometrische Charakterisierung von Organkulturen des humanen Limbusepithels.

Transplantations of limbus epithelium play a steadily increasing role in the therapy of chemical burns, recurrent erosions, and impaired differentiation of the limbus epithelium (LE). To assess the vitality of LE under different culture conditions, LE was excised from 30 patients and cultivated in media with serum (F12 + 10% FCS) and without it (S4 and F12). AE5 antigen (64K keratin) was expressed by the LE specimens in these 3 media with an intensity similar to that of uncultivated specimens. All specimens strongly expressed EGF and PDGF-beta receptors under serum-free culture conditions, while serum-containing cultures reduced the expression of these receptors. Among the cells which migrated from the conjunctival preparations into the culture medium, connective tissue cells (anti-vimentin), macrophages (mac 1 and mac 2 antibodies), epithelial cells (AE5 antibody) and cells expressing class II antigen (Tü 39 and Tü 22 antibody) were determined. Only in the S4 medium were neither macrophages nor class II antigen-positive cells found. The epithelial thickness was unchanged before and after incubation with S4 medium. The two other media caused a reduction in thickness of the epithelium. The average size of the epithelial cells increased non-significantly in all cultures. Ultrastructurally, the organ cultures incubated in S4 medium showed practically no degenerative cell changes. On the basis of the criteria used here for quality checks of LE organ cultures, S4 appears to be the medium best suited on the basis of functional (PDGF-beta and EGF receptors) and morphological criteria (keratin expression, epithelial thickness and epithelial cell size).

[Videolaparoscopy and carcinoma of the gallbladder]. / Videolaparoscopia e carcinoma della colecisti.

There have been several reports claiming that there is a risk that laparoscopic cholecystectomy might worsen the prognosis of unexpected gallbladder cancer. The objective of this study was to evaluate which factors influence the prognosis of such cancers. A clinicopathological study was conducted in 25 patients with unexpected gallbladder cancer. The results of 10 patients undergoing laparoscopic cholecystectomy were compared with those of 15 patients undergoing open cholecystectomy. Correlations were evaluated between cumulative survival rates and seven prognostic factors, namely, age, sex, histopathological grade, pathological stage, occurrence of bile spillage, type of cholecystectomy (laparoscopic or open) and additional surgical treatments. Seven patients after laparoscopic cholecystectomy (70%) and 9 patients after open cholecystectomy (64%) had cancer recurrence: the difference was not statistically significant. There was a statistically significant correlation between survival rate and tumour stage (P < 0.01) and occurrence of bile spillage (P < 0.05). There was no difference in survival depending on whether cholecystectomy was carried out using laparoscopic or traditional techniques. Laparoscopic cholecystectomy does not adversely affect the prognosis of unexpected gallbladder cancer. Once the histological findings have been examined, the surgeon will decide whether it is necessary to extend surgery, regardless of whether laparoscopic or open cholecystectomy is carried out.

Long-term therapy with adefovir dipivoxil in hepatitis B e antigen-negative patients developing resistance to lamivudine.

BACKGROUND: The efficacy of long-term adefovir dipivoxil monotherapy or combination of adefovir and lamivudine in hepatitis B e antigen (HBe-Ag)-negative lamivudine-resistant chronic hepatitis B (CHB) patients is still under investigation. AIM: To assess the safety and efficacy of the long-term adefovir treatment alone or in combination with lamivudine in HBe-Ag-negative CHB patients who had developed breakthrough because of lamivudine-resistant mutants. METHODS: Fifty-nine patients received combination therapy, while 23 switched to adefovir alone after a 3-month course of combination therapy. RESULTS: The median follow-up after adefovir's onset was 31 (18-40) months. Baseline characteristics were similar between the two groups. At 12 and 24 months, 69% and 89% of patients receiving combination therapy and 73% and 82% of patients receiving adefovir monotherapy had serum HBV-DNA <10(4) copies/mL (P > 0.5). Normalization of alanine aminotransferase levels occurred in 81% and 79% of patients receiving combination vs. 61% and 53% receiving adefovir monotherapy at 12 and 24 months, respectively (P > 0.50). Virological breakthroughs because of adefovir-resistant mutants occurred in five patients under adefovir monotherapy and in none receiving combination therapy (P = 0.001). No one developed decompensated liver disease or hepatocellular carcinoma during follow-up. Re-introduction of lamivudine in adefovir-resistant patients achieved reduction in HBV-DNA and biochemical remission, but re-emergence of lamivudine mutants was observed in one patient after 7.5 months. CONCLUSION: In HBe-Ag-negative CHB patients with lamivudine resistance, adding adefovir to continuing lamivudine therapy maximizes anti-viral efficacy because of absence of viral resistance.

[Differential therapy of cerebral arteriovenous malformations. An analysis with reference to personal microsurgery experiences]. / Die Differentialtherapie zerebraler arteriovenöser Missbildungen. Eine Analyse unter Berücksichtigung eigener mikrochirurgischer Erfahrungen.

A total of 126 patients (63 female, 63 male) underwent microsurgical removal of their cerebral arteriovenous malformations (AVMs) by the same surgeon. The mean age at surgery was 34.7 (6-72) years. The symptoms were intracerebral hemorrhage (37.3%), seizure disorder (34.9%) or focal neurological deficits and minor symptoms. According to the Spetzler/Martin scale, 20.6% of the AVMs were grade I, 28.6% grade II, 32.5% grade III, 14.3% grade IV and 4% grade V. In all, 78 AVMs (61.9%) were located in functionally important brain regions. The series was split into three different groups: small AVMs under 3 cm in diameter (n = 62/49.2%), medium-sized AVMs (n = 58/46%) and large AVMs (n = 6/4.8%). Seventeen patients had preoperative embolization of their AVM. All patients had postoperative angiographic control and 3- and 6-month follow-up. One patient died (0.8%), and another one (0.8%), in whom the AVM was incompletely resected, suffered a secondary hemorrhage. Seventeen (27.4%) of the patients with small AVMs developed transient neurological worsening post-operatively, which remained permanently significant in 3.2%. The respective numbers for the patients with medium-sized AVMs were 48.3% and 10.3% and for the large AVMs 83.3% and 33.3%. The results of microsurgical removal of cerebral AVMs can still be considered superior to the results of stereotactic radiosurgical treatment available from the literature-even for small AVMs. This is due to immediate exclusion of the AVM under direct local control of the angioarchitecture and thereby a reduced risk of secondary hemorrhaging and a decreasing morbidity rate with increasing time after the operation. Radiosurgical treatment requires a 2-year latency period for obliteration and carries a mortality rate of up to 12.5% and a rate of unexpected side effects of up to 20%. This treatment should be reserved for small, deep, surgically inaccessible AVMs or used as part of a multimodality treatment regimen consisting of partial embolization, partial excision and consecutive radiation of the residual nidus in initially very large AVMs. Embolization therapy-such as radiosurgery-carries a significant risk of morbidity (8%) and a mortality rate of up to 6%. It should only be considered for AVMs that are expected to be fully obliterated afterwards, or for primary inoperable AVMs that are to be changed into operable ones by embolization. Size reduction of otherwise operable AVMs does not justify the additional risk of embolization. Close collaboration of the specialties involved is desirable.

Specific transcellular staining of microglia in the adult rat after traumatic degeneration of carbocyanine-filled retinal ganglion cells.

The present work was undertaken to assess the fate of ganglion cell debris in the axotomized retina of adult rats and employed a new technique to label phagocytosing microglia via the internalized material. In the main experiment, transection axotomy was performed on the intraorbital segment of the optic nerve, and a fast-transported, vital fluorescent styryl dye (4Di-10ASP) was deposited at the ocular stump of the nerve in order to pre-label retrogradely the ganglion cells destined to die because of the axotomy. Optic nerve transection resulted in progressive degradation of ganglion cell axons, perikarya, and dendrites within the retina and in release of fluorescent material, which was then incorporated into cells identified as microglia. No other retinal cells stained, although astrocytes and Müller's cells also responded to neuron degeneration by accumulating glial fibrillary acidic protein. Incorporation of labelled material into microglia topo-chronologically paralleled the ganglion cell degeneration starting within the optic fibre layer (OFL) and proceeding towards the ganglion cell layer (GCL) and the inner plexiform layer (IPL) of the affected retina. Long-term labelling of microglia monitored up to 3 months after optic nerve transection indicated that labelled microglial cells persisted within the retina. Microglia displayed a strong territorial arrangement within the GCL and IPL, and staggered, bilaminated distribution in both layers. These studies directly prove that microglia in the retina can be transcellularly labelled during traumatic degeneration of ganglion cells. The findings suggest that microglial cells play an important role in axotomy-induced wound healing and removal of cell debris.

[Cerebrogenic ECG changes after severe subarachnoid hemorrhage from an internal carotid artery aneurysm--differential diagnosis of acute myocardial infarct]. / Zerebrogene EKG-Veränderungen nach schwerer Subarachnoidalblutung aus einem Arteria-carotis-interna-Aneurysma--Differentialdiagnose des akuten Myokardinfarktes.

ECG-changes simulating acute posterior myocardial infarction were observed in a 62-year-old woman 16 days after acute subarachnoid hemorrhage. An acute myocardial ischemia was excluded by enzyme laboratory tests and by coronary angiography. The transient ECG-changes can be explained by short-term spasms of small distal arterioles in the heart, which were affected by a derangement of autonomic function. The present case demonstrates ECG-changes in a patient with subarachnoid hemorrhage very late after the acute event. Therefore, patients with intracranial hemorrhage should have a prolonged electrocardiographical aftercare. ECG-changes in patients with subarachnoid hemorrhage were discussed as a specific parameter describing the degree of intracranial damage and as a predictive value for a poor outcome. Because of ventricular arrhythmias and the occurrence of sudden cardiac death in patients with subarachnoid hemorrhage critical care monitoring should be performed after detection of new ECG-changes.

The influence of barbiturates on cerebral metabolism in patients with borderline cerebrovascular reserve during intraoperative transient carotid occlusion.

Sixty patients with borderline or frank insufficiency of their cerebrovascular reserve undergoing carotid endarterectomy were given enough short acting barbiturates, during cross clamping of the internal carotid artery, to cause EEG burst suppression. Arterial and venous concentrations of lactate were measured in blood samples taken before, 30 min after occlusion of the artery and 10 min after reperfusion. The amount of lactate produced depended on the length of time of burst suppression; the shorter it lasted, the larger the amount of lactate produced. Only in patients with the shortest burst suppression times did the blood lactate levels rise above normal levels. The lactate levels can be used as indicators of how effective barbiturates are being in preventing ischaemia during the time of carotid artery occlusion.

Modification of glassy carbon surfaces with synthetic laminin-derived peptides for nerve cell attachment and neurite growth.

Interactions between cultured nerve cells and surfaces are of importance for the implantation of biocompatible electrode materials such as glassy carbon (GC). Since implants serve as recording sensors in prosthetic neuroscience, we investigated whether coating electrodes with certain laminin derivatives containing the peptide sequences SIKVAV, CDPGYIGSR, PDSGR, YFQRYLI, and RNIAEIIKDA influences neuronal adhesion and neurite outgrowth in vitro. The coating of GC was performed by electrochemical polymerization and, for comparison, by adsorption or covalent coupling. Electrochemical polymerization is suitable for the coupling of peptides to GC, as shown by amino acid analysis and sequencing. Embryonic chicken retinal ganglion cells and brain cells (days E7 or E17) were used for both attachment and growth studies. Surfaces made by electrochemical polymerization of peptides were more efficient than those made by adsorption or covalent coupling of peptides. Synthetic cyclic peptide derivatives of CDPGYIGSR and 18-mer SIKVAV were found to be more efficient than the linear peptides. Competitive effects that resulted in a decreased cell attachment could be found upon application of soluble peptides. Nevertheless, irrespective of the method of coating, peptides were less efficient compared with the whole laminin molecule, as expected from its multiple adhesion sites. When small GC pins were implanted into the brain of E17 chicken after coating with the 18-mer SIKVAV peptide, nerve cell attachment was observed in vivo. The results suggest that chronically implantable materials may exert a higher neurocompatibility when coated with synthetic peptides.