[Unilateral spinal anesthesia : Literature review and recommendations]. / Einseitige Spinalanästhesie : Literaturübersicht und Handlungsempfehlung.

Unilateral spinal anesthesia is a cost-effective and rapidly performed anesthetic technique. An exclusively unilateral block only affects the sensory, motor and sympathetic functions on one side of the body and offers the advantages of a spinal block without the typical adverse side effects seen with a bilateral block. The lack of hypotension, in particular, makes unilateral spinal anesthesia suitable for patients with cardiovascular risk factors e. g. aortic valve stenosis or coronary artery disease. Increasing numbers of surgical procedures are now being performed on an outpatient basis. Until now, spinal anesthesia has been considered unsuitable for this, not only because of the high incidence of intraoperative hypotension and postoperative urinary retention but also because of the prolonged postoperative stay before home discharge. This is not the case with unilateral spinal anesthesia: motor function returns rapidly, the incidence of urinary retention is extremely low, and patients are usually eligible for home discharge sooner than after bilateral spinal anesthesia or general anesthesia. The success of the technique depends on a number of factors. In addition to the local anesthetic, its concentration and dose, and the baricity of the injected solution, the shape of the spinal needle, the injection speed, the patient's position during injection, and the time the patient remains in this position after injection are equally important parameters. A number of intrathecally applied adjuvant drugs are used to give a more intense and/or longer-lasting block. For this review, we collated the published data on unilateral spinal anesthesia from journals with an impact factor greater than 1.0 and defined an optimized method for performing the technique. In order to achieve an exclusively unilateral block one should use 0.5 % hyperbaric bupivacaine injected at a rate of 0.33 ml/min or slower. During the injection and the following 20 min the patient should lie in the lateral decubitus position on the side intended for surgery with knees drawn to the chest. An injection of 5 mg (1 ml) hyperbaric bupivacaine 0.5 % provides an hour-long block to T 12, and a dose of 7.5 to 10 mg (1.5-2.0 ml) extends the block to T 6. Adding clonidine (0.5 to 1.0 µg/kg BW) to the injection prolongs the duration of the block to approximately two to three hours. During the 20-minute fixation period, the cephalad spread of the block can be influenced to a certain extent by raising or lowering the head of the table.

Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial.

In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), long-term disease control can only be achieved by allogeneic hematopoietic stem cell transplantation (HSCT). We studied the safety and efficacy of clofarabine-based salvage therapy. The study was designed as phase II, multicenter, intent-to-transplant (ITT) study. A total of 84 patients with r/r AML were enrolled. All patients received at least one cycle of CLARA (clofarabine 30 mg/m(2) and cytarabine 1 g/m(2), days 1-5). Chemo-responsive patients with a donor received HSCT in aplasia after first CLARA. Generally, HSCT was performed as soon as possible. The conditioning regimen consisted of clofarabine (4 × 30 mg/m(2)) and melphalan (140 mg/m(2)). The median patient age was 61 years (range 40-75). On day 15 after start of CLARA, 26% of patients were in a morphologically leukemia-free state and 79% exposed a reduction in bone marrow blasts. Overall, 67% of the patients received HSCT within the trial. The primary end point, defined as complete remission after HSCT, was achieved by 60% of the patients. According to the ITT, overall survival at 2 years was 43% (95% confidence interval (CI), 32-54%). The 2-year disease-free survival for transplanted patients was 52% (95% CI, 40-69%). Clofarabine-based salvage therapy combined with allogeneic HSCT in aplasia shows promising results in patients with r/r AML.

Discovery of τ Neutrino Appearance in the CNGS Neutrino Beam with the OPERA Experiment.

The OPERA experiment was designed to search for ν_{µ}→ν_{τ} oscillations in appearance mode, i.e., by detecting the τ leptons produced in charged current ν_{τ} interactions. The experiment took data from 2008 to 2012 in the CERN Neutrinos to Gran Sasso beam. The observation of the ν_{µ}→ν_{τ} appearance, achieved with four candidate events in a subsample of the data, was previously reported. In this Letter, a fifth ν_{τ} candidate event, found in an enlarged data sample, is described. Together with a further reduction of the expected background, the candidate events detected so far allow us to assess the discovery of ν_{µ}→ν_{τ} oscillations in appearance mode with a significance larger than 5σ.

Selective unilateral spinal anaesthesia for outpatient knee arthroscopy using real-time monitoring of lower limb sympathetic tone.

Selective unilateral spinal anaesthesia is a useful approach for ambulatory lower limb surgery because it allows more rapid home discharge compared to bilateral block. Infrequent use is due to the fact that obtaining selective unilateral block can be difficult, requiring attention to technique. We present a method with a high success rate that uses real-time monitoring of the sympathetic activity of the legs. In this prospective study, 56 patients scheduled for ambulatory knee arthroscopy had spinal anaesthesia in the lateral recumbent position, with hyperbaric bupivacaine 0.5% injected at 0.33 ml/min up to a maximum dose of 5 mg. Sympathetic tone of the legs was monitored by plantar electrical dermal resistance. The clinical effect was assessed by loss of sensation and muscle strength. The haemodynamic course and adverse events were monitored. The motor block was strictly unilateral in 55 patients (98%) and the sensory block was strictly unilateral in 53 patients (94%). The median decrease in systolic blood pressure was 6 mmHg. The time from subarachnoid puncture to arrival in the recovery room was 73±23 minutes; the duration of stay in the recovery room was 70±30 minutes. Three patients with a well-established block of adequate extent required conversion to general anaesthesia because of tourniquet pain. Urinary retention only occurred in the sole patient with bilateral block. This method of performing selective unilateral spinal anaesthesia using real-time monitoring of sympathetic tone of the legs has a high success rate and is associated with rapid eligibility for home discharge.

One-dimensional weak antilocalization due to the berry phase in HgTe wires.

We study the weak antilocalization (WAL) effect in the magnetoresistance of narrow HgTe wires fabricated in quantum wells with normal and inverted band ordering. Measurements at different gate voltages indicate that the WAL is only weakly affected by Rashba spin-orbit splitting and persists when the Rashba splitting is about zero. The WAL amplitude in wires with normal band ordering is an order of magnitude smaller than for wires with an inverted band structure. These observations are attributed to the Dirac-like dispersion of the energy bands in HgTe quantum wells. From the magnetic-field and temperature dependencies we extract the dephasing lengths and band Berry phases. The weaker WAL for samples with a normal band structure can be explained by a nonuniversal Berry phase which always exceeds π, the characteristic value for gapless Dirac fermions.

Backscattering of Dirac fermions in HgTe quantum wells with a finite gap.

The density-dependent mobility of n-type HgTe quantum wells with inverted band ordering has been studied both experimentally and theoretically. While semiconductor heterostructures with a parabolic dispersion exhibit an increase in mobility with carrier density, high-quality HgTe quantum wells exhibit a distinct mobility maximum. We show that this mobility anomaly is due to backscattering of Dirac fermions from random fluctuations of the band gap (Dirac mass). Our findings open new avenues for the study of Dirac fermion transport with finite and random mass, which so far has been hard to access.

Continuous biogas production from fodder beet silage as sole substrate.

Since April 2000 a two-step anaerobic plant with two subsequent 500 m3 reactors has been producing biogas from fodder beet silage (pH 3.4-4.1) as the sole substrate. The plant is located at Kirchlengern near Bielefeld, Germany. Initially the reactors were inoculated with swine manure at 37 degrees C. After a start-up phase the process was sustained at pH 7.5-8.0 by feeding the silage as sole substrate with an HRT of about 55 d twice a day. Parallel to the biogas plant at Kirchlengern four one-step laboratory reactors were continuously driven at temperatures of 37 degrees C, 45 degrees C, 60 degrees C and 65 degrees C. They were fed with the same silage, but only once per day (one impulse). The organic loading rate (OLR) was adjusted to 3.9 g volatile solids (VS)/(l*d) with a concomitant hydraulic retention time (HRT) of 27 d. There was no problem with starting the reactors, but after 86 days the volumetric gas production of the 65 degrees C reactor ceased and a high amount of approximately 65 mM propionate could be determined. By decreasing the temperature down to 60 degrees C a stable reactor performance was recovered for a period of at least 600 further days. Interestingly microscopic analyses revealed that the morphology of methanogenic bacteria in the 60 degrees C was quite different from the 37 and 45 degrees C reactor exhibiting only rodlike methanogens whereas at 37 degrees C coccoid morphotypes besides rodlike methanogens were dominant. In a 55 degrees C reactor (separate experiment) a mixture of coccoid and rodlike methanogens established. During impulse feeding with 3.9 g (VS)/(l*d) it was observed that the quickest recovery of gas production, the pH, CH4 and CO2 content as well as the redox value could be observed at 37 degrees C or at 45 degrees C. Recovery of 75% gas volume (related to the value before or after impulse feeding) was obtained after 5.5 and 7.5 h of feeding time point whereas the 60 degrees C reactor needed 16 h. Slight significant differences were seen in the spectrum of volatile fatty acids (VFA) reaching at 37 degrees or 45 degrees C its maximum with 10-30 mM total VFA at 2-3 h after feeding. After this the VFA level declined to nearly zero (except for the 60 degrees C reactor). Therefore the 37 degrees C reactor was favoured. A double experiment with a second 37 degrees C reactor was started by a somewhat different inoculation procedure from the remaining 3 reactors, but revealed similar results. An impulse feeding experiment with a very high OLR of 16.5 g (VS)/(l*d) lasting 1 week offered a stable reactor performance with a peak GPR of up to 24 l/(l reactor *d) and an HRT of 5.45d. Therefore a long term operation with an HRT of only 7.5 days and an OLR of 12 g (VS)/(l*d) should be possible. By increasing the temperature no significantly different specific gas production rates and methane yields could be observed, e.g. it gave 600-7001 biogas from 1 kg VS. The corresponding methane content ranged between 62-64%. With a methane content of 63 +/- 1% a yield of 40.1 +/- 2 m3 methane/ton fresh fodder beet silage was obtained.

Development and characterization of a tamoxifen-resistant breast carcinoma xenograft.

A human tamoxifen-resistant mammary carcinoma, MaCa 3366/TAM, originating from a sensitive parental xenograft 3366 was successfully established by treatment of tumour-bearing nude mice with 1-50 mg kg(-1) tamoxifen for 3 years during routine passaging. Both tumours did not differ significantly in OR- and PR-positivity, however, when compared with the sensitive tumour line, the mean OR content of the TAM-resistant subline is slightly lower. An OR-upregulation following withdrawal of oestradiol treatment was observed in the parental tumours but not in the resistant xenografts. Following long-term treatment with tamoxifen, the histological pattern of the breast carcinoma changed. The more differentiated structures being apparent after treatment with 17beta-oestradiol in the original 3366 tumour were not induced in the resistant line. Tamoxifen failed to induce a tumour growth inhibition in comparison to the tamoxifen-sensitive line. The pure anti-oestrogen, ICI 182 780, revealed cross-resistance. Sequence analysis of the hormone-binding domain of the OR of both lines showed no differences, suggesting that either mutations in other regions of the OR are involved in the TAM-resistance phenotype or that mechanisms outside of this protein induced this phenotype. Oestrogen and anti-oestrogen regulate pS2 and cathepsin D expression in 3366 tumours as in the human breast cancer cell line MCF-7. The resistant 3366/TAM tumours have lost this regulation. The established breast cancer xenografts 3366 and 3366/TAM offer the possibility of investigating mechanisms of anti-oestrogen resistance in an in vivo situation. They can be used to test novel approaches to prevent, or to overcome, this resistance in a clinically related manner.

Relation of oestradiol-mediated growth stimulation with the expression of c-erbB-2 protein in xenotransplanted oestradiol-receptor-positive and -negative breast carcinomas.

Attempts were made to correlate growth effects induced by oestradiol and tamoxifen with the hormonal regulation of c-erbB-2 protein in experiments in vivo. We report here the responsiveness of four xenotransplanted oestrogen-receptor(ER)-positive and four ER-negative human mammary carcinomas to oestradiol and tamoxifen. Oestradiol in a dose of 0.5 mg/kg significantly increased the growth of the ER-positive mammary carcinomas 3366, MCF-7, 4134 and 4049, but not the ER-negative tumours 4000, 4296 and MT-3. However, within the group of the ER-negative breast carcinomas the tumour 4151 ES deviates from this growth behaviour, as we could prove an estrogen induced growth. The stimulation of tumour growth by oestradiol was always accompanied by a down-regulation of c-erbB-2 protein both in the ER-positive mammary carcinomas and in the ER-negative mammary carcinoma 4151 ES. Tamoxifen significantly inhibited the growth of the ER/PR-positive mammary carcinomas 3366 and MCF-7 but not the ER-positive/PR-negative mammary carcinomas 4049 and 4134. In the group of ER-negative mammary carcinomas only the growth of the oestrogen-responsive tumour 4151 ES was significantly inhibited by tamoxifen. The inhibition of tumour growth by tamoxifen was correlated with a reversion of the oestradiol-induced down-regulation of c-erbB-2, also in the ER-negative/oestradiol-responsive mammary carcinoma 4151 ES. From our results we hypothesize that the oestrogen-dependent growth of ER-negative breast carcinoma 4151 ES could also be correlated with the oestradiol-regulated expression of c-erbB-2 protein.

Establishment and characteristics of two new human mammary carcinoma lines serially transplantable in nude mice.

Two human mammary carcinomas of postmenopausal women were successfully transplanted into nude mice. Both tumours were classified as epidermal-growth-factor-, oestradiol- and progesterone-receptor-negative and c-erbB2-protein-positive. Histological studies of the primary tumours (4000 and 4151) revealed ductal invasive mammary carcinomas. In the first passages the precondition for the growth of breast carcinoma 4000 were pretreatments of the nude mice with oestradiol and peanut oil before transplantation. The mammary carcinomas 4000 and 4151 described here are suitable for in vivo testing of antineoplastic substances and for biological studies.

Establishment and characterization of a new human oestradiol- and progesterone-receptor-positive mammary carcinoma serially transplantable in nude mice.

A human mammary carcinoma originating from a postmenopausal patient was successfully transplanted into nude mice. According to the adopted criteria the tumour proved to be oestradiol- and progesterone-receptor-positive. Histological studies of the patient tumour revealed a ductal invasive mammary carcinoma with 80% tubular growth pattern. Following transplantation the adenoid structures decreased to 30%; the mitosis rate and grade of malignancy increased. Treatment of the nude mice with 20 micrograms oestradiol benzoate/mouse caused a loss of the oestradiol receptor of the mammary carcinoma. The mammary carcinoma 3366 can be used for testing of antineoplastic substances, antihormones and for studies in regard to down-regulation or blocking of hormone receptors and possible consequences for therapies.

Characterization of two human mammary carcinomas, MT-1 and MT-3, suitable for in vivo testing of ether lipids and their derivatives.

The human mammary carcinomas MT-1 and MT-3 originate from surgical material and were transplanted in nude mice. Both tumors have been classified as estradiol- and progesterone receptor-negative. Therapeutic doses of hormones and anti-hormones remained without growth inhibitory effect. MT-1 and MT-3 proved to be sensitive to conventional cytostatic drugs used for treatment of mammary carcinomas; striking is their sensitivity to ether lipids. Therefore, they are considered suitable tumor models for this class of substances.

Chromate effects on red cells membranes.

The modification of human erythrocyte membrane proteins by chromate previously had been investigated by kinetic (4) and electrophoretic techniques (5). In the Coulter Counter we now observed that chromate (10 mM) caused an increase in the intracellular resistivity but also an augmentation of the critical voltage where the membrane resistance breaks down owing to electroporation. Furthermore, a slight chromate-induced augmentation of echinocyte shape was observed. Also, chromate causes the intracellular pH to shift to higher values.

Chromate effects on human erythrocytes--investigations on sulphydryl groups, cross-linking of membrane proteins and electromechanical properties in the coulter-counter.

The carcinogen chromate inactivates its own carrier in the human erythrocyte membrane. This effect is paralleled by the inhibition of chromate uptake by the sulphydryl reagents N-ethylmaleimide and iodoacetate. However, no decrease in the sulphydryl content of erythrocyte membranes treated with up to 100 mM chromate was detected. By SDS gel electrophoresis, a limited cross-linking of red cell membrane proteins was found at 100 mM chromate, but not at cytotoxic concentrations up to 10 mM chromate. Erythrocytes treated with up to 100 mM chromate exhibited no change in the "dielectric breakdown", i.e. the sharp decrease of the apparent cellular volume at a critical detector current.

Modification of the erythrocyte anion carrier by chromate.

It was confirmed that chromate is taken up by human erythrocytes via the general anion carrier. The chromate flux is unidirectional and chromium is accumulated within red cells presumably due to intracellular reduction of Cr(VI) to Cr(III). The analysis of the initial rates of uptake of chromate revealed two distinct uptake mechanisms at low (0.001-0.01 mM) and at high (0.05-1.0 mM) chromate concentrations. After prolonged incubation with 1 mM chromate, the subsequent rate of uptake of chromate was decreased. It is suggested that the decreased uptake is due to a modification of the anion-transport protein by chromate.

[Appendicitis and pregnancy]. / Appendizitis und Schwangerschaft.

In the years of 1981 to 1983 15 pregnant patients had to be operated on because of suspected appendicitis. In 10 patients acute symptoms of inflammation of the appendix could be proved histologically. Morbidity rate was 2.1 per thousand related to a over-all of 4766 births in the 3 years.