Estradiol prodrugs (EP) for efficient oral estrogen treatment and abolished effects on estrogen modulated liver functions.

Oral compared to parenteral estrogen administration is characterized by reduced systemic but prominent hepatic estrogenic effects on lipids, hemostatic factors, GH-/IGF I axis, angiotensinogen. In order to avoid such adverse metabolic effects of oral treatment, estradiol (E2) prodrugs (EP) were designed which bypass the liver tissue as inactive molecules. Carbone17-OH sulfonamide [-O2-NH2] substituted esters of E2 (EC508, others) were synthesized and tested for carbonic anhydrase II (CA-II) binding. CA II in erythrocytes is thought to oppose extraction of EP from portal vein blood during liver passage. Ovariectomized (OVX, day minus 14) rats were orally treated once daily from day 1-3. Sacrifice day 4. Uteri were dissected and weighed. Cholesterol fractions and angiotensinogen were determined in plasma. Oral E2 and ethinyl estradiol (EE) generated dose related uterine growth and important hepatic estrogenic effects. EP induced uterine growth at about hundred-fold lower doses. This was possible with almost absent effects on plasma cholesterol or angiotensinogen. Preliminary pharmacokinetic studies with EC508 used intravenous and oral administration in male rats. Resulting blood levels revealed complete oral bioavailability. Further high blood- but low plasma concentrations indicated erythrocyte binding of EC508 in vivo as potential mechanism of low extraction at liver passage. Very high systemic estrogenicity combined with markedly lower or absent adverse hepatic estrogenic effects is evidence for a systemic release of E2 from sulfonamide EP. In conclusion, tested oral EP bypass the liver in erythrocytes furnishing systemic estradiol at hydrolysis. This mechanism avoids the hepatic estrogenic impact of conventional oral estrogen therapy.

[Potential of Information and Communications Technology to Improve Intersectoral Processes of Care: A Case Study of the Specialised Outpatient Palliative Care]. / Potenziale der Informations- und Kommunikationstechnologie zur Optimierung intersektoraler Versorgungsprozesse: Ein Fallbeispiel der spezialisierten ambulanten Palliativversorgung.

OBJECTIVE: The added value of information and communications technologies should be demonstrated precisely in such areas of care in which the importance of intersectoral and interdisciplinary cooperation is particularly high. In the context of the accompanying research of a supply concept for palliative care patients, the potential of a digital documentation process was comparatively analysed with the conventional paper-based workflow. METHODS: Data were collected in the form of a multi-methodological approach and processed for the project in 3 stages: (1) Development and analysis of a palliative care process with the focus on all relevant steps of documentation. (2) Questionnaire design and the comparative mapping of specific process times. (3) Sampling, selection, and analysis of patient records and their derivable insights of process iterations. RESULTS: With the use of ICT, the treatment time per patient is reduced by up to 53% and achieves a reduction in costs and workload by up to 901 min. The result of an up to 213% increase in the number of patient contacts allows a higher continuity of care. Although the 16% increase in documentation loyalty improves the usability of cross-team documented information, it partially extends the workload on the level of individual actors. By using a digital health record around 31% more patients could be treated with the same staffing ratio. CONCLUSIONS: The multi-stage analysis of the palliative care process showed that ICT has a decisive influence on the process dimension of intersectoral cooperation. Due to favourable organisational conditions the pioneering work of palliative care also provides important guidance for a successful use of ICT technologies in the context of innovative forms of care.

[Soft tissue reconstruction in the extremities and the head and neck area using the anterolateral thigh free flap]. / Die freie anterolaterale Oberschenkellappenplastik zur Weichteilrekonstruktion an den Extremitäten und im Kopf-Hals-Bereich.

OBJECTIVE: Stable soft tissue coverage of exposed bone, tendons, or hardware in the extremities or the head and neck area with a microsurgically grafted free flap. INDICATIONS: Soft tissue defects measuring up to 42 × 15 cm in the extremities and the head and neck region. CONTRAINDICATIONS: Previous surgery or trauma in the anterolateral thigh region. Insufficient personnel and/or technical resources. SURGICAL TECHNIQUE: A line is marked from the anterior superior iliac spine to the superolateral patella pole, approaching the intermuscular septum between the rectus femoris and vastus lateralis muscle. The flap is centred on this line and after medial incision the perforators of the descending branch of the lateral circumflex femoral artery are identified and dissected to their origin. Afterwards the lateral incision is carried out and flap dissection is completed. After flap transfer microsurgical anastomoses are performed and the flap is sutured to the recipient region. POSTOPERATIVE MANAGEMENT: Flap monitoring for 1 week. Strict elevation and immobilization after flap transfer to the extremities; bedrest for 1 week. Thrombosis prophylaxis. RESULTS: From 2008-2011, 41 free anterolateral thigh flaps in 5 women and 36 men with an average age of 53 years (38-70 years) were performed for microsurgical soft tissue reconstruction. Total flap loss rate was 2.4 % and reoperation due to complications, e.g., hematoma, problems with microsurgical anastomosis, and partial flap loss was necessary in 13.8 % of patients.

Breast cancer management and outcome according to surgeon's affiliation: a population-based comparison adjusted for patient's selection bias.

BACKGROUND: Studies have reported that breast cancer (BC) units could increase the quality of care but none has evaluated the efficacy of alternative options such as private BC networks, which is our study objective. PATIENTS AND METHODS: We included all 1404 BC patients operated in the public unit or the private network and recorded at the Geneva Cancer Registry between 2000 and 2005. We compared quality indicators of care between the public BC unit and the private BC network by logistic regression and evaluated the effect of surgeon's affiliation on BC-specific mortality by the Cox model adjusting for the propensity score. RESULTS: Both the groups had high care quality scores. For invasive cancer, histological assessment before surgery and axillary lymph node dissection when indicated were less frequent in the public sector (adjusted odds ratio (OR): 0.4, 95% confidence interval (CI) 0.3-0.7, and OR: 0.4, 95% CI 0.2-0.8, respectively), while radiation therapy after breast-conserving surgery was more frequent (OR: 2.5, 95% CI 1.4-4.8). Surgeon affiliation had no substantial effect on BC-specific mortality (adjusted hazard ratio (HR): 0.8, 95% CI 0.5-1.4). CONCLUSIONS: This study suggests that private BC networks could be an alternative to public BC units with both structures presenting high quality indicators of BC care and similar BC-specific mortality.

[Split thickness skin graft for coverage of soft tissue defects]. / Spalthauttransplantation zur weichteildefektdeckung.

OBJECTIVE: Coverage of skin or soft tissue defects of various sizes by transplantation of spit thickness skin grafts. INDICATIONS: Skin or soft tissue defects of any size or location as long as there is a good blood supply to the wound bed. CONTRAINDICATIONS: Wound bed providing poor blood supply (e.g., tendon or bone), vessels or nerve without soft tissue coverage, any kind of implant material which is not covered by vital soft tissue. Relative contraindications include defect position at the flexion side of joints or other mechanically stressed locations (e.g., heel, neck) and local infection. SURGICAL TECHNIQUE: By meticulous debridement of the recipient site and coagulation of venous bleedings, the recipient site is prepared for skin grafting. Thereafter, the split thickness skin graft is harvested and, if necessary, modified by the meshing procedure. Then, the skin graft is placed in the defect and fixated at the wound margins. To promote healing, a special compression dressing is used to cover the split thickness skin graft. In case of uneventful wound healing, this dressing should be left in place for 5 days. POSTOPERATIVE MANAGEMENT: After removal of the compression dressing, daily changes are done using double layers of fatty gauze, alternated with periods without dressing. In the case of uneventful healing, the skin transplant can be covered starting in week 2 with a thin film of cream ointment. RESULTS: Split thickness skin grafting is a routine maneuver in reconstructive surgery and allows predictable, good results. Partial skin graft losses are mostly due to a combination of inadequate debridement and local infection. If the operation in done technically correct, total graft losses are rare.

[Special training therapy to reduce inflammation in Anti-Jo-1 syndrome]. / Spezielle Trainingstherapie zur Reduktion der Inflammation bei Anti-Jo-1-Syndrom.

A 46-year-old patient was frequently seen with a medically treated Anti-Jo-1 syndrome. The patient had already been treated with azathioprine and oral corticosteroids on account of decreasing lung function, dyspnoea, fatigue, and beginning signs of myositis. Although high doses of steroids and azathioprine were administered, the muscleskeletal syndromes increased steadily. The patient used to be an active long-distance runner (20 km), but now was unable to perform that kind of physical exercise. It was decided to start a treatment with the GalileoTM training device for active muscle training of the lower extremities. Before and after three months of training the following assessment was performed: measurement of health-related quality of life (St. Georges respiratory questionnaire, SGRQ), ultrasound measurement of the cross-sectional area of the quadriceps muscle, 6 minute walk test (6 MWT), lung function testing, and assessment of serum markers of inflammation (TNF-alpha, interleukin-8, CRP, CK, myoglobin). After only two months, training with the GalileoTM five times a week has improved the patient's conditions dramatically. The training will be continued.

[The anterolateral thigh flap: its versatility in oncological soft tissue reconstruction of the head and neck region]. / Der anterolaterale Oberschenkellappen : Seine Vielseitigkeit bei der onkologischen Weichteilrekonstruktion im Kopf-Hals-Bereich.

The anterolateral thigh flap (ATL) has become a standard procedure in reconstructive microsurgery. In this study the results with the ALT for reconstruction in the head and neck area after tumor resection in 33 patients were retrospectively analyzed. Patients included 28 men and 5 women aged 47-70 years who suffered from intraoral and extraoral tumors. Satisfactory soft tissue coverage could be achieved in all patients and no flaps were lost. The ALT is a versatile free flap enabling reliable soft tissue reconstruction of complex defects in the head and neck region. Flap dissection and preparation of the recipient area can usually be performed simultaneously. Additional advantages include the long and strong caliber vascular pedicle, the low donor site morbidity and the different possibilities of tissue composition, making the ALT a workhorse flap in modern reconstructive microsurgery.

Retinotomy and silicone oil for detachments complicated by anterior inferior proliferative vitreoretinopathy.

AIM: To describe a subset of patients with recurrent retinal detachments caused by anterior intraretinal and subretinal proliferative vitreoretinopathy (PVR), which required greater than 180 degrees retinotomy and silicone oil tamponade. METHODS: Interventional case series. Forty-one patients underwent >180 degrees retinotomy, anterior retinectomy, removal of subretinal membranes, laser to the retinotomy edge and silicone oil tamponade. Risk factors for detachment, prior surgical history and PVR location were examined. Main outcomes included change in visual acuity, recurrent detachment and postoperative complications. RESULTS: Cataract extraction (49%), high myopia (29%) and lattice degeneration (27%) were preoperative risk factors. The average number of prior procedures for retinal attachment was 2.3 (SD 0.9). The majority of detachments were inferior and related to anterior intraretinal and subretinal PVR. Twenty-four patients (59%) saw 20/200 or better. Eleven patients (27%) had poor vision (<20/400) at the end of follow-up. Thirty-seven retinas (90%) remained attached. Increased rates of postoperative corneal decompensation (p<0.0001) and silicone oil in the anterior chamber (p<0.0001) were statistically significant markers of poor visual outcome. CONCLUSIONS: Patients with complex PVR requiring a large retinotomy often had similar presurgical conditions. A large inferior retinotomy effectively addressed proliferations where they most frequently occur, and silicone oil was beneficial.

Consequences of one-lung flooding: a histological and immunological investigation.

BACKGROUND: Videothoracoscopic lung sonography after partial fluid instillation could be a new method for endoscopic detection of lung lesions. Histopathological consequences of unilateral diagnostic or therapeutic lung flooding under bronchoalveolar lavage has yet to be defined. The aim of the study was to investigate histological and immunohistological alterations induced by one-lung flooding (OLF). METHODS: 13 female pigs were subjected to OLF (15 ml isotonic electrolyte solution per kg for 60 minutes), and lung tissue was collected 30 minutes, 2 hours, 24 hours, 48 hours, 6 days, 8 days, and 10 weeks after flooding. Histological examinations and immunohistochemical labeling for surfactant protein A (SP-A) were performed. Cellular proliferation was measured by Ki67 immunohistochemical labeling. Apoptosis was detected through enzymatic in-situ labeling of apoptosis-induced DNA strand breaks by means of the TUNEL (TdT-mediated dUTP nick end labeling) method. RESULTS: Histological analyses revealed the presence of inflammatory cell infiltrates in the interstitium at 24 hours after OLF. However, no destruction of the alveolar wall and no pulmonary oedema were observed. In addition, OLF was not associated with any decrease in surfactant protein A immunoreactivity. Two hours after OLF, the number of apoptotic cells was increased (OLF: 7% vs. CONTROL: 0.6%, p < 0.05), but cellular proliferation was unchanged. Conversely, at 48 h after OLF, the number of apoptotic cells had returned to control levels, but cellular proliferation had increased (OLF: 5% vs. CONTROL: 1.1%, p < 0.05). Cellular proliferation returned to baseline levels eight days after OLF. CONCLUSIONS: These data demonstrate that OLF is not associated with destruction of the alveolar texture, atelectasis-provoking surfactant loss, or any irreversible damage to the pulmonary parenchyma. Lung flooding for the purpose of videothoracoscopic lung sonography is safe and justifiable. But repeated lung flooding under bronchoalveolar lavage involving the same lung area within 1 week is not to be recommended.

[Preparation for clinical introduction of advanced laparoscopic procedures: laparoscopic renal autotransplantation]. / Vorbereitung zur klinischen Etablierung fortgeschrittener urologischer Operationstechniken: Laparoskopische Autotransplantation am Tiermodell.

BACKGROUND: After long term clinical training at teaching hospitals, individuals or complete teams have reported on the establishment of laparoscopic nephrectomy and prostatectomy. This, however, is difficult to realize at many clinics due to the current staffing situation. In the following an alternative approach will be presented. METHODS: After 50 hours of practice on a pelvic trainer during which the laparoscopic handling and especially various suturing techniques were learnt (A) a total of 15 pigs (approx. 40 kg, in general aesthesia, right sided positioned, with 7 ports) have been operated from February to August 2006: 1. laparoscopic nephrectomy, 2. laparoscopic in-situ cold perfusion, 3. laparoscopic renal autotransplantation (B). Directly after this a two month clinical training at a recognized laparoscopic center took place (C). RESULTS: After completion of phase A, an extended experimental operation phase B followed, marked by complications such as: bleeding (n=5), skin emphysemas (n=3), technical failures (n=2), non-optimal placement of ports (n=6), problems with placement the cold perfusion catheters (n=7), and unsuitable surgical instruments (n=2). Eleven laparoscopic nephrectomies were successful; only during the last three operations a sufficient end-to side anastomosis has been achieved (anastomosis time range 80110 min of which was 50% in cold ischemia). During the external clinical training (C) (through 2. and 1. assistance) five endoscopic extraperitoneal prostatectomies (surgery time range 145-235 min) and two radical nephrectomies have been independently carried out (180-230 min). CONCLUSIONS: Using the pig model laparoscopic renal autotransplantation ideally combines ablative and reconstructive operation techniques. For this reason it is especially suitable for young urologists learning to perform nephrectomies and prostatectomies. For beginners in laparoscopy this entails long but mentor independent learning phases A, B thereby shortening the subsequent clinical training at the teaching hospital (C).

[Surgical outcome in pertrochanteric femur fracture: the impact of osteoporosis. Comparison between DHS and percutaneous compression plate]. / Operationsergebnisse nach pertrochantärer Femurfraktur: Welchen Einfluss hat die Osteoporose? Vergleich zwischen DHS und perkutaner Kompressionsplatte.

AIM: The dynamic hip screw (DHS) often shows an impared outcome and a high incidence of therapeutic failure in patients with osteoporotic pertrochanteric femur fractures. This is caused predominantly by a fracture collapse and appears often in unstable fractures (31A2, 31A3). In a prospectively documented clinical study, we examined whether or not the percutaneous compression plate (PCCP, Gotfried) offers advantages following osteoporotic fractures. METHOD: From August 2003 to December 2005, 103 patients underwent internal fixation with the DHS (n = 40, age 76.1, ASA 2.9) or with the PCCP (n = 63, age 76.9, ASA 2.8). Proximal femurs were classified with the Singh grading system, which uses six grades of trabecular patterns to describe the degree of osteoporosis. Reexamination of the patients (27 DHS, 43 PCCP) was performed on average 18 months later. RESULTS: The PCCP was implanted into very osteoporotic femurs (Singh 2) in less time than the DHS (47 vs. 79 min). These patients treated with PCCP showed no difference in blood loss, but tended to have better outcomes (Merle d'Aubigné, Harris hip score) than those treated with DHS. Life quality, subjectively measured with the visual analogue score, was significantly better in the PCCP group with high-grade osteoporosis (Singh 2). The outcome after implantation of the PCCP was not correlated to the Singh index in stable or in unstable fractures. Mechanical complications occurred especially in unstable fractures (re-operation rate: DHS 4/18 [22 %], PCCP 3/29 [10 %], p = 0.266), without correlation to the Singh index. Excluding the avoidable complication of loosening of the screw-barrel portion, the re-operation rate for the PCCP was 3 % (cut-out: 1/29, p = 0.042) in unstable fractures. CONCLUSION: Use of the minimally invasive PCCP technique in osteoporotic pertrochanteric femur fractures provides an alternative to the dynamic hip screw, especially with regard to surgical time and outcome. Advantages occurred also in the re-operation rate following fracture fixation complications. The cut-out rate was significantly lower than in the DHS group in unstable fractures.

[CT-guided interventions in children]. / Computertomografisch gesteuerte Interventionen bei Kindern.

In pediatric CT-guided interventions specific features have to be taken into account. Due to a lack of cooperation or limited ability to cooperate, procedures are often performed using analgosedation or general anesthesia. To provide radiation protection, justified indication for CT-guided intervention is necessary and sonography and MRI are to be preferred whenever possible. CT examinations also need to be dose-adapted with sequential scanning and a tube voltage and tube current reduction compared to pediatric diagnostic CT studies must be ensured. Gonad shields are recommended for male patients. Biopsy device selection depends on the assumed tumor entity since histology and also immunohistochemical, molecular pathological and cytogenetical analysis are necessary to differentiate pediatric tumors (small, round, blue cell tumors). In addition to diagnostic procedures, therapeutic interventions (drainage, injection therapies, neurolysis, and radiofrequency ablation) can also be used in children and can provide an alternative to surgery in selected cases. With justified indications and precise performance, CT-guided interventions can be successful in pediatric patients with limited risks.

Impact of familial risk factors on management and survival of early-onset breast cancer: a population-based study.

This population-based study evaluates the impact of a strong family history of breast cancer on management and survival of women with early-onset disease. We identified all breast cancer patients

Short-term human chondrocyte culturing on oriented collagen coated gelatine scaffolds for cartilage replacement.

The biological, biochemical, mechanical, and structural properties of artificial scaffolds for tissue engineering are known to be of great importance. Therefore, in this study a hydrogel derived scaffold with biomechanical and structural properties similar to native articular cartilage was synthesized. The gelatine-based hydrogel was processed by freeze-structuring, structuring by electrochemical water-decomposition, freeze-drying and chemical fixation resulting in a defined scaffold-structure. By electron microscopy a perpendicular pore-channel structure was verified with channel diameters between 30 microm and 70 microm. Mechanical testing showed mechanical properties similar to native cartilage. Human chondrocytes from biopsy samples were cultivated on these hydrogel scaffolds for three days. Two different cell densities (1.2 x 10(6) cells/cm3 and 12.0 x 10(6) cells/cm3) were used for cultivation. Histology of the cell seeded artificial scaffolds demonstrated vital cells that are widely distributed within the scaffold and mimic a columnar arrangement.

Culture of haematopoietic cells in a 3-D bioreactor made of Al2O3 or apatite foam.

Foams of Al2O3 and apatite ceramics with interconnecting pores were produced using a new technique. The surfaces of the ceramics served as substrates for the culture of human peripheral and bone marrow derived stem cells. Up to 27 days the cells were kept in culture where they proliferated and developed into different morphologies consistent with bone marrow cell lines.

Development of a model food for microwave processing and the prediction of its physical properties.

Although microwave processes in the food industry such as microwave pasteurisation or microwave drying are already in use, most of their optimisation is still based on trial-and-error. To model these processes, knowledge of different physical properties of the food material is indispensable. In order to guarantee constant product properties a model food was developed imitating real food properties and showing physical and microbial stability over several months. In this manuscript the prediction of these physical properties and the comparison of the model food with a real food will be shown.

Purification and partial characterization of the major allergen, Cav p 1, from guinea pig Cavia porcellus.

BACKGROUND: Allergic reaction to guinea pig has been recognized as a problem in domestic settings and work environments for many years. Until recently, limited information was available on the properties of guinea pig allergen(s). In this study the major allergen Cav p 1 was characterized and the N-terminal amino-acid sequence was determined. METHODS AND RESULTS: Sera from 40 patients with IgE-mediated allergy to guinea pigs were investigated by means of immunoblotting using extracts prepared from guinea pig hair and urine. Three major allergens were identified within both sources with molecular weights (MW) of 8 kDa, 17 kDa and 20 kDa, respectively. From aqueous hair extracts the 20 kDa allergen (Cav p 1) was purified to homogeneity by anion exchange chromatography and reverse-phase HPLC and the N-terminal amino-acid sequence was determined. On the basis of the 15 residues, 57% identity was obtained from computer search with a sub-sequence of MUP (major urinary protein), a member of the lipocalin superfamily. Allergenic relationships among guinea pig allergens derived from various sources (hair and urine) or different animal species (mouse, rat, cat) were studied by ELISA inhibition assays. Neither urine of mouse, rat and cat, nor hair extracts of rat and cat produced appreciable inhibitions in guinea pig ELISA. CONCLUSION: Although the physicochemical characteristics of isolated Cav p 1 are very similar to those for other rodent allergens and furthermore partial sequence identity with Mus m 1 was found, it is clearly shown here to be an immunologically independent major allergen.

The effects of increasing concentrations of isoflurane and desflurane on pulmonary perfusion and systemic oxygenation during one-lung ventilation in pigs.

UNLABELLED: During one-lung ventilation (OLV), hypoxic pulmonary vasoconstriction (HPV) reduces venous admixture and attenuates the decrease in arterial oxygen tension by diverting blood from the nonventilated lung to the ventilated lung. In vitro, desflurane and isoflurane depress HPV in a dose-dependent manner. Accordingly, we studied the effects of increasing concentrations of desflurane and isoflurane on pulmonary perfusion, shunt fraction, and PaO(2) during OLV in vivo. Fourteen pigs (30-42 kg) were anesthetized, tracheally intubated, and mechanically ventilated. After placement of femoral arterial and thermodilution pulmonary artery catheters, a left-sided double-lumen tube (DLT) was placed via tracheotomy. After DLT placement, FIO(2) was adjusted at 0.8 and anesthesia was continued in random order with 3 concentrations (0.5, 1.0, and 1.5 minimal alveolar concentrations) of either desflurane or isoflurane. Differential lung perfusion was measured with colored microspheres. All measurements were made after stabilization at each concentration. Whereas mixed venous PO(2), mean arterial pressure, cardiac output, nonventilated lung perfusion, and shunt fraction decreased in a dose-dependent manner, PaO(2) remained unchanged with increasing concentrations of desflurane and isoflurane during OLV. In conclusion, increasing concentration of desflurane and isoflurane did not impair oxygenation during OLV in pigs. IMPLICATIONS: In an animal model of one-lung ventilation, increasing concentrations of desflurane and isoflurane dose-dependently decreased shunt fraction and perfusion of the nonventilated lung and did not impair oxygenation. The decreases in shunt fraction are likely the result of anesthetic-induced marked decreases in cardiac output and mixed venous saturation.