Haftung des gerichtlichen Sachverständigen – Widerruf gutachterlicher Behauptungen

Ohne Zusammenfassung     

Quantification of intracranial contribution to rheoencephalography by a numerical model of the head.

OBJECTIVES: Partial contributions of intracranial and extracranial circulation to rheoencephalography (REG) remain uncertain. The main goal of this work is to determine theoretically the capability of REG techniques to reflect intracranial blood flow. METHODS: Head and current injection electrodes were computationally modeled to assess REG sensitivity to brain and scalp conductivity changes. Data obtained were related to tissue perfusions to calculate the partial contribution of cerebral blood perfusion to REG I, REG II and monopolar REG and to assess their amplitudes. RESULTS: When REG I and monopolar REG were used, the theoretical maximum of intracranial contribution was reached with large current injection electrodes, being 8% for REG I and 12% for monopolar REG. However, some specific REG II electrode arrangements showed a nil contribution of the extracranial circulation and a minimum influence of the electrode size. CONCLUSIONS: These results may explain the disagreement on REG origin and suggest a theoretically optimum electrode arrangement.     

The identification of KRAS mutations at codon 12 in plasma DNA is not a prognostic factor in advanced non-small cell lung cancer patients

Background

Qualitative analysis of circulating DNA in the blood is a promising non-invasive diagnostic and prognostic tool. Our aim was to study the association between the presence of KRAS mutations at codon 12 and several clinical variables in advanced non-small cell lung cancer (NSCLC) patients.

Methods

We examined 308 stage IIIB and IV NSCLC patients who were treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the plasma using commercial adsorption columns. The KRAS mutational status was determined by an RT-PCR method that is based on allelic discrimination.

Results

The median age of the patients was 60 years [31-80], 84% were male, 98% had a performance status of 0-1 and 84% of the patients were in stage IV. The histological subtypes were as follows: 30% squamous cell carcinoma (SCC), 51% adenocarcinoma (ADC) and 19% others. Of the 277 response-evaluated patients, 1% achieved a complete response (CR), 26% achieved a partial response (PR), 34% had stable disease (SD) and 39% had progressive disease (PD). Additionally, 27 (8.8%) patients had KRAS mutations; 26 had a KRAS codon 12 TGT mutation, and 1 had a codon 12 GTT mutation. Plasmatic KRAS mutations were found in patients presenting SCC or ADC. Patients with KRAS mutations in plasma DNA had a median progression free survival (PFS) of 5.77 months [3.39-8.14], whereas for patients with wild-type (wt) KRAS, the PFS was 5.43 months [4.65-6.22] (p = 0.277). The median overall survival (OS) in KRAS-mutated patients was 9.07 months [4.43-13.70] vs 10.03 months [8.80-11.26] in wt patients (p = 0.514).

Conclusions

In advanced NSCLC patients, there were no significant differences between patients with or without KRAS mutations in plasma-free DNA with respect to the baseline characteristics, response rates, PFS or OS.     

Incidence and type of complications in non-operated patients at a surgical ward

Background

This study was designed to analyze a group of non-operated patients admitted to our surgical ward for incidence and type of documented complication. We classified and categorised these complications according to the definition of the Association of Surgeons of the Netherlands (ASN). Our main interest was to identify adverse events for non-operated patients that are caused by medical management and thus preventable.

Methods

Complications were prospectively collected in our registry, which is part of an electronic medical patient file, and in retrospective analysed. All non-operated patients admitted to our surgical ward between January 2003 and January 2006 have been analysed for type and incidence of complications.

Results

We recorded 437 complications in 364 (8%) of 4602 non-operated patients and we categorised 196 (45%) of these events in the Hospital - Provider group. In this last category 161 (82%) events were related to medical management and appeared to be preventable. Numerous different types of complications were recorded (n = 69) among the 437 events. Of all the complications, 75 (17%) were found to be a negative effect/failure of therapy.

Conclusion

The incidence of complications in non-operated patients at our surgical ward was 8%, with a great variety in types of events documented. Almost half of all complications (45%) were recorded in the Hospital-Provider category and appeared to be preventable, which needs further investigation.     

p38α limits the contribution of MAP17 to cancer progression in breast tumors

MAP17 is a small, 17-kDa, non-glycosylated membrane protein that is overexpressed in a percentage of carcinomas. In the present work, we have analyzed the role of MAP17 expression during mammary cancer progression. We have found that MAP17 is expressed in 60% human mammary tumors while it is not expressed in normal or benign neoplasias. MAP17 levels increased with breast tumor stage and were strongly correlated with mammary tumoral progression. A significant increase in the levels of reactive oxygen species (ROS) was observed in MAP17-expressing cells, as compared with parental cells. This increase was further paralleled by an increase in the tumorigenic capacity of carcinoma cells but not in immortal non-tumoral breast epithelial cells, which provides a selective advantage once tumorigenesis has begun. Expression of specific MAP17 shRNA in protein-expressing tumor cells reduced their tumorigenic capabilities, which suggests that this effect is dependent upon MAP17 protein expression. Our data show that ROS functions as a second messenger that enhances tumoral properties, which are inhibited in non-tumoral cells. We have found that p38α activation mediates this response. MAP17 triggers a ROS-dependent, senescence-like response that is abolished in the absence of p38a activation. Furthermore, in human breast tumors, MAP17 activation is correlated with a lack of phosphorylation of p38α. Therefore, MAP17 is overexpressed in late-stage breast tumors, in which oncogenic activity relies on p38 insensitivity to induce intracellular ROS.