Further studies on the hepatoprotective effects of Cochlospermum tinctorium rhizomes.

The hepatoprotective activity of the rhisome of Cochlospermum tinctorium was investigated using carbon tetrachloride toxicity on mouse and tert-butyl hydroperoxide in vitro induction of lipid peroxidation and hepatocyte lysis. Aqueous, hydro-ethanolic and ethanolic extracts showed significant dose-dependent hepatoprotective actions. The ethanolic extract showed a hepatoprotective activity at lower doses than silymarin. The ethanolic and hydro-ethanolic extracts exhibited remarkable effects against the induction of lipid peroxidation and hepatocyte lysis; the aqueous extract showed comparatively weaker effects. These differences were related to the chemical composition of the extracts. Among the identified constituents of the drug, phenolic and polyphenolic compounds (gallic and ellagic acids, ellagitannins, flavonoids), carotenoids, triterpenes could be related to the biological activity.     

Human brain atlas: For high-resolution functional and anatomical mapping

We present the new computerized Human Brain Atlas (HBA) for anatomical and functional mapping studies of the human brain. The HBA is based on many high-resolution magnetic resonance images of normal subjects and provides continuous updating of the mean shape and position of anatomical structures of the human brain. The structures are transformable by linear and nonlinear global and local transformations applied anywhere in 3-D pictures to fit the anatomical structures of individual brains, which, by reformatting, are transformed into a high-resolution standard anatomical format. The power of the HBA to reduce anatomical variations was evaluated on a randomized selection of anatomical landmarks in brains of 27 young normal male volunteers who were different from those on whom the standard brain was selected. The HBA, even when based only on standard brain surface and central structures, reduced interindividual anatomical variance to the level of the variance in structure position between the right and left hemisphere in individual brains. © 1994 Wiley-Liss, Inc.     

Dissolution rate improvement of poorly water-soluble drugs obtained by adsorbing solutions of drugs in hydrophilic solvents onto high surface area carriers.

The dissolution rate of the model drugs carbamazepine and nifedipine was improved by adsorbing solutions of the drugs in hydrophilic non-volatile or volatile solvents onto carriers with a large surface area. This was accomplished by dissolving the drug in methanol or the non-toxic hydrophilic liquids PEG 400 or 2-pyrrolidone, and adsorbing these solutions onto the surface of silica (Aerosil) or crosslinked polyvinylpyrrolidone (Kollidon CL-M). The solvent binding capacities decreased in the order of methanol, PEG 400, 2-pyrrolidone for Aerosil 200, 300, 380 and for Kollidon CL-M. Kollidon bound less liquid than Aerosil because of the smaller surface area. Differential scanning calorimetry measurements showed higher interactions between drugs and Kollidon compared to Aerosil, suggesting a low aggregation of precipitated drug particles. The drug release from the adsorbent systems was enhanced when compared to micronized drug and independent of the drug loading in the investigated range. The drugs were also dissolved in various liquid, paste-like or solid solubilisers (polyoxyl-40-hydrogenated castor oil (Cremophor RH 40), macrogol-15-hydroxystearate (Solutol HS), poloxamers (Lutrol F68, Pluronic F87NF and Pluronic L44NF) and adsorbed onto Kollidon. These adsorbent systems also exhibited an increased dissolution rate when compared to pure drug.     

Coronary atherosclerosis of the donor heart--impact on early graft failure.

OBJECTIVE: Due to the shortage of donor hearts, the criteria for organ acceptability have been considerably extended and donor grafts with coronary atherosclerosis are among those offered. This study evaluated whether and to what degree pre-existing coronary atherosclerosis may be acceptable. METHODS: A total of 1253 consecutive HTx recipients were investigated retrospectively for donor-transmitted coronary atherosclerosis (DCAS). Donor-transmitted coronary atherosclerosis was defined as focal atherosclerosis with stenosis of at least 50%. Inclusion criteria were absence of pre-HTx angiogram but performance of angiogram or autopsy within 6 months after heart transplantation. Kaplan-Meier analysis and log-rank test were used. RESULTS: Eighty-five out of 1253 (6.8%) cases were excluded, since coronary evaluation was not performed within 6 months (n=45) or hearts had undergone pre-transplant angiography (n=40). In 1086 patients no donor-transmitted coronary atherosclerosis was found (NDCAS group) and in 82 patients (7%) donor-transmitted coronary atherosclerosis was diagnosed by angiography (n=49) or autopsy (n=33). Single-vessel donor-transmitted coronary atherosclerosis was found in 53/82 patients (DCAS1 group) and double- or triple-vessel donor-transmitted coronary atherosclerosis in 26/82 patients (DCAS2/3 group). Three of the 82 patients with donor-transmitted coronary atherosclerosis were excluded since the autopsy report was unclear regarding degree of atherosclerosis. Early after heart transplantation the 30-day mortality in the NDCAS and DCAS1 groups was 12.2% versus 13.2% whereas in the DCAS2/3 group it was 61.5%. Beyond the first year the annual decrease with and without donor-transmitted coronary atherosclerosis (single-vessel disease) is comparable. CONCLUSIONS: Donor screening without coronary angiogram overlooks significant atherosclerotic lesions in a considerable number of cases (7.0%). Therefore, angiographic donor screening should be performed. Donor grafts with single-vessel coronary atherosclerosis may be accepted as marginal hearts; however, in our opinion, revascularisation (CABG, PTCA) should be considered. Grafts with two- or even three-vessel coronary atherosclerosis seem to have a serious risk for early graft failure. Beyond the first year the outcome of healthy grafts and grafts with donor-transmitted coronary atherosclerosis seems to be comparable.     

Degradable injectable bone cement in maxillofacial surgery: indications and clinical experience in 27 patients.

BACKGROUND: A carbonated apatite cement (NORIAN SRS) was used as a bone mineral substitute for the calvaria or viscerocranium in 27 patients. It has the consistency of a paste and hardens at physiologic pH and body temperature due to dahllite crystallization, which has the stoichiometric formula Ca(8.8)(HPO(4))(0.7)(PO(4))(4.5)(CO(3))(0.7)(OH)(1.3). MATERIAL AND METHODS: The cement was used for posttraumatic bone defects in the orbital, periorbital or malar regions (nine patients), posttraumatic deformities of the frontal bone (six patients), tumour-dependent bony defects of the calvaria (two patients) and posttraumatic or cystic defects of the mandible (five patients). In another five patients, the material was used to augment the atrophic anterior mandible in combination with the insertion of dental implants. Follow-up varied between 6 and 40 months (mean: 29 months). RESULTS: There was no inflammatory reaction surrounding the implanted material. There was no sign of infection in any of the patients and only one case of partial wound dehiscence with superficially exposed material. The defect fillings and augmentations were successful in all patients. None of the 19 dental implants which were inserted in combination with the material showed any sign of infection or loosening. Also, there was no loosening of the implants after loading (mean follow-up: 15 months). From the check-up radiographs, the material could be seen as a dense, radio-opaque structure. There were no material fractures or dislocations. Radiologically, the material seemed to be completely replaced by bony tissue after 30 months. CONCLUSION: Our 5-year clinical experience suggests that the material is a suitable bone mineral substitute for cranio-maxillofacial surgery especially for moderate-sized defects of the calvaria and forehead bone. It has advantages over preformed, solid bone substitute materials, and, due to its initial plasticity and eventual great compressive strength, it can also stabilize dental endosseous implants in the atrophic mandible.     

Detection of disseminated tumor cells in the lymph nodes of colorectal cancer patients using a real-time polymerase chain reaction assay

Introduction Postoperative treatment for colorectal cancer depends on tumor stage as defined by the International Union Against Cancer (UICC). Adjuvant chemotherapy is not recommended in patients without lymph node involvement (UICC stages I and II). As many as 20–30% of these patients, however, will develop recurrence. Aims and objectives We conducted this study to determine the presence of disseminated tumor cells in the lymph nodes by quantitative real-time polymerase chain reaction (QRT-PCR) for cytokeratin 20 (CK20) in an attempt to provide supplementary information compared to histopathological findings. Materials and methods Using a standard QRT-PCR assay, we examined primary tumors and 391 lymph nodes from 31 patients with completely resected colorectal cancer. Results Of the 31 primary tumors, 29 were positive for CK20 by QRT-PCR. Discussion An examination of the lymph nodes from the 29 patients with CK20-positive primary tumors revealed that 35 (92.1% sensitivity) of the 38 histopathologically positive lymph nodes and 54 (16.7%) of the 324 histopathologically negative lymph nodes were positive by molecular analysis. CK20 expression was detected in 10 (100%) of 10 patients with a histopathologically positive lymph node status (pN1). In 9 (47.4%) of 19 patients with negative histopathological results (pN0), we detected a CK20 mRNA signal in at least one lymph node. Whereas eight patients with histopathologically negative lymph nodes could be upstaged on the basis of the molecular findings, no patient would be downstaged. Conclusion Our results suggest that QRT-PCR for CK20 is a useful tool for the quantitative detection of micrometastases in the regional lymph nodes. We introduce a standardized procedure that integrates a molecular diagnostic technique in the clinical staging.     

Parallel imaging reconstruction for arbitrary trajectories using k-space sparse matrices (kSPA).

Although the concept of receiving MR signal using multiple coils simultaneously has been known for over two decades, the technique has only recently become clinically available as a result of the development of several effective parallel imaging reconstruction algorithms. Despite the success of these algorithms, it remains a challenge in many applications to rapidly and reliably reconstruct an image from partially-acquired general non-Cartesian k-space data. Such applications include, for example, three-dimensional (3D) imaging, functional MRI (fMRI), perfusion-weighted imaging, and diffusion tensor imaging (DTI), in which a large number of images have to be reconstructed. In this work, a systematic k-space-based reconstruction algorithm based on k-space sparse matrices (kSPA) is introduced. This algorithm formulates the image reconstruction problem as a system of sparse linear equations in k-space. The inversion of this system of equations is achieved by computing a sparse approximate inverse matrix. The algorithm is demonstrated using both simulated and in vivo data, and the resulting image quality is comparable to that of the iterative sensitivity encoding (SENSE) algorithm. The kSPA algorithm is noniterative and the computed sparse approximate inverse can be applied repetitively to reconstruct all subsequent images. This algorithm, therefore, is particularly suitable for the aforementioned applications.     

Atypical forms of isolated partial atrioventricular septal defect increase the risk of initial valve replacement and reoperation.

OBJECTIVE: We consider the short- and long-term outcomes of the repair of the isolated partial atrioventricular (AV) septal defect to determine the role played by the atypical forms on the initial AV valve replacement and on the risk of reoperation. METHODS: Two hundred and eight patients underwent an operation for this malformation between 1974 and 2001. Clinical and echocardiographic examinations were performed on all patients, the AV valve regurgitation was graded from 1 to 4 and a residual interatrial shunt was sought. Median age at the intervention was 5.8 years (3 months to 67 years). RESULTS: Median follow-up time was 7.5 years (range 0-22.6 years). The cumulative 30-day, 5- and 20-year survival rates were 96.5, 95.4 and 94.6%, respectively. AV valve replacement was associated with a high mortality (P<0.001). A reoperation was performed on 12 patients (5.7%) including six patients within less than a 30-day period, especially to repair residual AV valve regurgitation. We performed four AV valve repairs by annuloplasty and six AV valve replacements. Two patients who had initially undergone an AV valve replacement underwent a reoperation for valve thrombosis. The cumulative 30-day, 5- and 20-year rates of freedom from reoperation were 96.5, 93.6 and 83%, respectively. An atypical form was present in 24 patients (11.5%) and was a risk factor for initial AV valve replacement (P<0.001) and for reoperation (P<0.001). A complete AV block occurred in 13 patients (6.2%), all of them within a 30-day period. The AV valve replacement was a high risk factor for a complete AV block (P<0.001). At the end of our study 180 patients (96%) were in NYHA I and 8 in NYHA II. CONCLUSIONS: The morbi-mortality of the isolated partial AV septal defect is primarily perioperative and is linked with the presence of an atypical form of the lesion. This atypical form was the main reason for reoperation for AV valve regurgitation. The AV valve replacement was associated with a high mortality and with the occurrence of complete AV block. Using a standardized technique, the AV septal defect can be repaired with excellent long-term clinical and echographic results.