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Modular Cloning (MoClo) is based on libraries of standardized genetic parts that can be directionally assembled via Golden Gate cloning in one-pot reactions into transcription units and multigene constructs. Here, a team of bachelor students established a MoClo toolkit for the protist Leishmania tarentolae in the frame of the international Genetically Engineered Machine (iGEM) competition. Our modular toolkit is based on a domesticated version of a commercial LEXSY expression vector and comprises 34 genetic parts encoding various affinity tags, targeting signals as well as fluorescent and luminescent proteins. We demonstrated the utility of our kit by the successful production of 16 different tagged versions of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein in L. tarentolae liquid cultures. While highest yields of secreted recombinant RBD were obtained for GST-tagged fusion proteins 48 h post induction, C-terminal peptide tags were often degraded and resulted in lower yields of secreted RBD. Fusing secreted RBD to a synthetic O -glycosylation SP20 module resulted in an apparent molecular mass shift around 10 kDa. No disadvantage regarding the production of RBD was detected when the three antibiotics of the LEXSY system were omitted during the 48-h induction phase. Furthermore, the successful purification of secreted RBD from the supernatant of L. tarentolae liquid cultures was demonstrated in pilot experiments. In summary, we established a MoClo toolkit and exemplified its application for the production of recombinant proteins in L. tarentolae ., Competing Interests: Conflict of Interest: The authors declare that there are no conflicts of interest., (Copyright: © 2024 Hieronimus et al.)

Glutaredoxins catalyze the reduction of disulfides and are key players in redox metabolism and regulation. While important insights were gained regarding the reduction of glutathione disulfide substrates, the mechanism of non-glutathione disulfide reduction remains highly debated. Here we determined the rate constants for the individual redox reactions between PfGrx, a model glutaredoxin from Plasmodium falciparum, and redox-sensitive green fluorescent protein 2 (roGFP2), a model substrate and versatile tool for intracellular redox measurements. We show that the PfGrx-catalyzed oxidation of roGFP2 occurs via a monothiol mechanism and is up to three orders of magnitude faster when roGFP2 and PfGrx are fused. The oxidation kinetics of roGFP2-PfGrx fusion constructs reflect at physiological GSSG concentrations the glutathionylation kinetics of the glutaredoxin moiety, thus allowing intracellular structure-function analysis. Reduction of the roGFP2 disulfide occurs via a monothiol mechanism and involves a ternary complex with GSH and PfGrx. Our study provides the mechanistic basis for understanding roGFP2 redox sensing and challenges previous mechanisms for protein disulfide reduction., (© 2024. The Author(s).)

Supernova remnants are among the most spectacular examples of astrophysical pistons in our cosmic neighborhood. The gas expelled by the supernova explosion is launched with velocities ~1000 kilometers per second into the ambient, tenuous interstellar medium, producing shocks that excite hydrogen lines. We have used an optical integral-field spectrograph to obtain high-resolution spatial-spectral maps that allow us to study in detail the shocks in the northwestern rim of supernova 1006. The two-component Hα line is detected at 133 sky locations. Variations in the broad line widths and the broad-to-narrow line intensity ratios across tens of atomic mean free paths suggest the presence of suprathermal protons, the potential seed particles for generating high-energy cosmic rays.

Due to accident severity and the extent of claim payments commuting accidents are a significant expense factor in the German industry. Therefore the aim of the present study was the identification of risk factors for commuting accidents in a German chemical company. A retrospective analysis of commuting accidents recorded between 1990 and 2003 was conducted in a major chemical company in Germany. A logistic regression-model was calculated in order to determine factors influencing the duration of work inability as a result of commuting accidents. The analysed data included 5,484 employees with commuting accidents. Cars (33.1%) and bicycles (30.5%) were the most common types of vehicles used by commuters who had an accident. The highest number of commuting accidents was observed in the age group under 26 yr. Accidents on the route from the work site to the worker's residence were less frequently observed, but they caused longer periods of work inability than accidents on the way to the work site. The longest periods of work inability were found in the groups of motorcyclists and older employees. The present study identifies specific groups at risk for commuting accidents. The data of the present investigation also underline the need for developing group specific prevention strategies.

Background: Seated working positions are often regarded as a cause for discomfort in the musculoskeletal system. Performing work in different working positions--that is, alternating between sitting and standing (sit-stand workstation paradigm)--could help reduce physical complaints., Objective: The questions were whether performing office work partly in a standing position leads to reduced complaints and whether standing would change the efficiency of data entry office work., Method: We investigated the effect of a sit-stand workstation paradigmd during experimental data entry office work on physical and psychological complaints and data entry efficiency by conducting a randomized controlled trial with 60 male participants ages 18 to 35 years., Results: In this experiment, musculoskeletal complaints were reduced by a sit-stand workstation paradigm. A trend could be identified indicating a small but nonsignificant loss of efficiency in data entry while standing., Conclusion: A sit-stand workstation paradigm reduces musculoskeletal complaints without considerably affecting data entry efficiency under the presented study conditions (young male participants, short duration, fixed and controlled sit-stand workstation paradigm, simulated experimental working condition)., Application: According to the present data, implementing a sit-stand workstation paradigm can be an effective workplace health intervention to reduce musculoskeletal complaints. This experiment encourages further studies on the effectiveness of a sit-stand workstation paradigm. Experimental research and field studies that prove the reduction of complaints when introducing a sit-stand workstation paradigm in the workplace could be the basis for evidence-based recommendations regarding such interventions.

Background: Currents of injury (COI) have been associated with improved lead performance during perioperative measurements in pacemaker and ICD implants. Their relevance on long term lead stability remains unclear., Methods: Unipolar signals were recorded immediately after active fixation ICD lead positioning, blinded to the implanting surgeon. Signals were assigned to prespecified COI types by two independent investigators. Sensing, pacing as well as changes requiring surgical intervention were prospectively investigated for 3 months., Results: 105 consecutive ICD lead implants were studied. All could be assigned to a particular COI with 48 type 1, 43 type 2 and 14 type 3 signals. Pacing impedance at implant was 703.8+/-151.6 Ohm with a significant COI independent drop within the first week. Sensing was 10.6mV+/- 3.7mV and pacing threshold at implant was 0.8+/-0.3mV at 0.5ms at implant. There was no significant difference between COI groups at implant and during a 3 months follow up regarding sensing, pacing nor surgical revisions., Conclusions: Three distinct patterns of unipolar endocardial potentials were observed in active fixation ICD lead implant, but COI morphology did not predict lead performance after 3 months.

This study demonstrates the applicability of pressurized stirred tank bioreactors for oxygen transfer enhancement in aerobic cultivation processes. The specific power input and the reactor pressure was employed as process variable. As model organism Escherichia coli, Arxula adeninivorans, Saccharomyces cerevisiae and Corynebacterium glutamicum were cultivated to high cell densities. By applying specific power inputs of approx. 48kWm(-3) the oxygen transfer rate of a E. coli culture in the non-pressurized stirred tank bioreactor was lifted up to values of 0.51moll(-1)h(-1). When a reactor pressure up to 10bar was applied, the oxygen transfer rate of a pressurized stirred tank bioreactor was lifted up to values of 0.89moll(-1)h(-1). The non-pressurized stirred tank bioreactor was able to support non-oxygen limited growth of cell densities of more than 40gl(-1) cell dry weight (CDW) of E. coli, whereas the pressurized stirred tank bioreactor was able to support non-oxygen limited growth of cell densities up to 225gl(-1) CDW of A. adeninivorans, 89gl(-1) CDW of S. cerevisiae, 226gl(-1) CDW of C. glutamicum and 110gl(-1) CDW of E. coli. Compared to literature data, some of these cell densities are the highest values ever achieved in high cell density cultivation of microorganisms in stirred tank bioreactors. By comparing the specific power inputs as well as the k(L)a values of both systems, it is demonstrated that only the pressure is a scaleable tool for oxygen transfer enhancement in industrial stirred tank bioreactors. Furthermore, it was shown that increased carbon dioxide partial pressures did not remarkably inhibit the growth of the investigated model organisms.

To determine the strenuousness and efficacy of therapy, the energy expenditure of 10 healthy and 10 hemiparetic subjects were measured while they walked on a treadmill that was combined with a robot-driven gait orthosis, the Lokomat, which physiologically exercises the legs of a patient on a moving treadmill. Subjects performed different Lokomat conditions after measurement of the baseline, i.e., standing in the Lokomat with 30% body weight support (BWS). Robotic strategies with a position control scheme used fixed gait patterns to produce the following conditions: walking with 100% BWS at a speed of 1 km/h versus 2 km/h and walking with 30% BWS at a speed of 1 km/h versus 2 km/h. Another robotic control option with a force control scheme allowed the force to be reduced on only one leg of the orthosis. In this option a reduction to 60% and to 0% assistance was tested. Oxygen consumption and heart rate were measured by a breath-by-breath respiratory gas analyzing system using standard open circuit methodology. The results for O(2) rate [ml/kg/min] indicate that: (1) walking in the Lokomat is not passive; (2) oxygen uptake is significantly increased due to an effect of loading during active stance phase; (3) speed is not a factor leading to increased oxygen consumption; (4) patients do not significantly increase their oxygen uptake due to the advanced force control scheme.

The effect of increased dissolved carbon dioxide concentrations on growth of Corynebacterium glutamicum was studied with continuous turbidostatic cultures. The carbon sources were either l-lactate or d-glucose. To increase the dissolved carbon dioxide concentration the carbon dioxide partial pressure of the inlet gas stream pCO2,IN was increased stepwise from 0.0003 bar (air) up to 0.79 bar, while the oxygen partial pressure of the inlet gas stream was kept constant at 0.21 bar. For each resulting carbon dioxide partial pressure pCO2 the maximum specific growth rate mu(max) was determined from the feed rate resulting from the turbidostatic control. On d-glucose and pCO2 up to 0.26 bar, mu(max) was mostly constant around 0.58 h(-1). Higher pCO2 led to a slight decrease of mu(max). On l-lactate mu(max) increased gradually with increasing carbon dioxide partial pressures from 0.37 h(-1) under aeration with air to a maximum value of 0.47 h(-1) at a pCO2 of 0.26 bar. At very high pCO2 (0.81 bar) mu(max) decreased down to 0.35 h(-1) independent of the carbon source.

Background and Purpose: The success of gait rehabilitation after stroke depends on active walking exercises. However, the disabling after-effects of stroke often make such exercises impossible at the onset of therapy. To facilitate treadmill training of paraparetic patients, a robot-driven gait orthosis (Lokomat) was developed. We investigated the effects of the Lokomat when used with hemiparetic patients., Methods: The authors conducted a randomized, controlled pilot study of 30 acute stroke survivors. The treatment group received 30 minutes of robotic training daily and the control group 30 minutes of conventional physiotherapy daily in addition to 30 minutes of conventional physiotherapy for each group. Outcome measures were independence of gait, gait speed, gait parameters, and body tissue composition., Results: After 4 weeks of therapy, the walking ability of the Lokomat group and the control group expressed as the functional ambulation classification was significantly improved. The functional ambulation category (median+/- interquartile range) was at baseline 0+/-0 in control and 0+/-1 in the therapy group and increased after therapy to 1+/-3 in both groups significantly (P=0.01). There was no significant difference in gain of these parameters between the groups. The Lokomat group had a significantly longer single stance phase (sec; mean+/-SEM) on the paretic leg when walking on the floor. At baseline, it was 0.19+/-0.17 and after therapy 0.49+/-0.07 (P=0.014). The control group had increased their body weight approximately 1.33+/-1.40 kg (mean+/-SEM; P=0.046), mostly as fat mass, whereas the Lokomat group had lost fat mass approximately -2.9+/-1.0 kg (mean+/-SEM; P=0.016) and increased their muscle mass approximately 3.36+/-1.4 kg (mean+/- SEM; P=0.031)., Conclusions: This pilot study indicates that Lokomat therapy is a promising intervention for gait rehabilitation. Although there was no difference between groups in gain of functional scores, the Lokomat group showed an advantage of robotic training over conventional physiotherapy in improvement of gait abnormality and body tissue composition.

Surgical treatment of extreme obesity can reliably achieve a significant weight loss. With interdisciplinary management, long-term therapeutic success is possible. Of particular importance, however, is the comprehensive education of the patient prior to surgery, and postoperative long-term care provided by the patient's own doctor.

Background: While numerous promising short-term results of open gastric bypass for morbid obesity were published, the long-term outcome of earlier versions was somewhat disappointing. Thus, it was not until 1993 that this procedure was reintroduced with current modifications and now performed laparoscopically. Published long-term results of gastric bypass are still lacking., Methods: Out of an original population of 195 patients, we retrospectively analyzed the outcome of 98 patients (82 women, 16 men, mean age 32 years [range 17-54], mean weight 132 kg [range 65-200], mean BMI 46.6 kg/m2) operated on in Erlangen with mean follow-up 22.9 years (range 16.5-25.4). 3 different bariatric operations were performed: horizontal gastroplasty (HGP, n=18), stapled Roux-en-Y gastric bypass (S-RYGBP, n=14) and transected Roux-en-Y gastric bypass (T-RYGBP, n=66). BMI and percentage of excess weight loss (%EWL) were calculated at time 0, and after 1, 2, 3, 10, 15, 20 and 25 years., Results: Statistically significant weight loss was found for the whole patient population at every postoperative time-point compared to preoperative values. Maximal weight loss was achieved mainly during the first 3 years. However, initial and long-term outcome after HGP was significantly worse than after S-RYGBP or T-RYGBP. Gender did not significantly influence the results., Conclusion: Traditional open gastric bypass resulted in acceptable and safe long-term weight reduction. It may be assumed that laparoscopic gastric bypass with modern tiny pouch volumes based on the lesser curvature achieves even better and life-long weight reduction.

Objective: Cross-sectional studies report a high prevalence of hypopituitarism after traumatic brain injury (TBI); however, no longitudinal studies on time of manifestation and reversibility exist. This study was conducted to assess hypopituitarism 3 and 12 months after TBI., Design: This was a prospective, longitudinal, diagnostic study., Methods: Seventy-eight patients (52 men, 26 women, mean age 36.0 years) with TBI grades I-III and 38 healthy subjects (25 men, 13 women, mean age 36.4 years) as a control group for the GHRH + arginine test were studied. The prevalence of hypopituitarism was assessed 3 and 12 months after TBI by GHRH + arginine test, short adrenocorticotropic hormone (ACTH) test, and basal hormone measurements in patients., Results: After 3 months, 56% of all patients had impairments of at least one pituitary axis with axes being affected as follows: gonadotropic 32%, corticotropic 19%, somatotropic 9% and thyrotropic 8%. After 12 months, fewer patients were affected, but in some cases new impairments occurred; 36% still had impairments. The axes were affected as follows after 12 months: gonadotropic 21%, somatotropic 10%, corticotropic 9% and thyrotropic 3%., Conclusions: Hypopituitarism occurs often in the post-acute phase after TBI and may normalize later, but may also develop after the post-acute phase of TBI.

Background: Eating behavior before surgery is considered to have great predictive value for the course of weight after surgery. The present study investigates the predictive value of three dimensions of eating behavior and disturbed eating on weight loss after gastric restriction surgery., Methods: 149 patients consisting of 47 males (32%), 102 females (68%), with mean age 38.8+10.3 years, were investigated by means of a structured interview and the Three Factor Eating Questionnaire (TFEQ) before (T1) and at least 12 months after (T2) (14.0+1.5 months) gastric restriction surgery., Results: Mean BMI before surgery was 50.9+/-8.1 kg/m2; postoperatively, the BMI decreased on average by 12.8 kg/m2 to 38.6+/-6.8 kg/m2 (t=22.7, P=0.000) at T2. Point-prevalence of Binge Eating Disorder (BED) according to DSM-IV was 2.0%, and lifetime-prevalence 7.4%, respectively. Of our sample, 20.1% reported current binge episodes without fulfilling all criteria for BED. An eating pathology consisting of continual eating ("grazing") was reported in 19.5% of the patients. At T2, patients with a weight loss of at least 25% of their pre-surgery weight indicated significantly less hunger and disinhibition compared with patients with less weight loss. Patients with a distinct craving for sweets after surgery lost significantly less weight. Patients with binge episodes or "grazing" before surgery did not differ in average weight loss from patients without binge episodes or "grazing"., Conclusion: Postoperative but not preoperative eating behavior is of predictive value for the extent of weight loss after gastric restriction surgery.

Bariatric surgery is well established to treat morbidly obese patients (BMI >40 kg/m(2)) with various techniques. Gastric-restriction procedures [adjustable gastric band, vertical banded gastroplasty (VBG)] reduce caloric intake and are well accepted (weight loss up to BMI 28-33 kg/m(2) after 5 years), but they are less effective in super-obese patients and in sweet-eaters. For that group combined techniques, such as duodenal switch, gastric bypass or bilio-pancreatic diversion, could produce a better weight loss (between 60 and 160 kg or BMI of 25-30 kg/m(2)) with acceptable long-term side effect; however, due to malabsorption, a lack of minerals and vitamins, even protein, could occur and have dangerous side effects. Both basic techniques have their place in the treatment of morbid obesity. The surgical approach-open or mini-invasive-is only of minor importance. Technical complications should be avoided, especially band dislocation (2-12%) or suture leak. Long-term follow-up is very important because obesity is a chronic disease with a high risk of recurrence, even after bariatric surgery.

The jejunoileostomy was a frequently used surgical procedure to treat morbid obese patients (obesity grade III) from 1970 to 1980. The observed weight loss was very good, 50-60 kg during the first 18 months after operation (n = 288). Even obesity-induced side effects were improved significantly. However, negative consequences and complications were seen all too often: chronic loss of electrolytes, protein and vitamins and diarrhea with perianal skin problems. Reoperations were often necessary due to renal stone formation, cholecystolithiasis or blind loop syndrome. Therefore this procedure was abandoned in favor of operations such as vertical banded gastroplasty or the adjustable gastric band. However, in special cases similar operations may be helpful if gastric restriction has failed.

To investigate long-term effects of hypoxia on a cellular level, di- and mesencephalic cell cultures were exposed to hypoxia on in vitro day 2 (incubation in culture medium, pO2 = 10-20 mmHg, 24 h) and on in vitro day 13 (incubation in an electrolyte solution, pO2 = 10-20 mmHg, 8 h). The numbers of neuron-specific enolase immuno-reactive (NSE-IR) and tyrosine hydroxylase immuno-reactive (TH-IR) neurons and the levels of dopamine, its main metabolites and the spontaneous and potassium-stimulated DA release were determined on DIV 15. Hypoxia on DIV 2 did not affect the numbers of NSE-IR and TH-IR neurons, but increased the dopamine content and dopamine release by about 100% in both di-and mesencephalic cultures. In addition, this hypoxia increased the vulnerability of non-TH-IR neurons to the second hypoxic episode applied during more advanced stages of the culture development on DIV 13. On the contrary, hypoxia exposure did not affect the vulnerability of TH-IR cells.

Background: Staple-line disruption is a common complication after vertical banded gastroplasty (VBG)., Methods: Of 655 patients who underwent VBG, a hole across the partition developed in 46 (7.02%)., Results: The original excellent weight loss from a BMI of 49.2 +/- 6.9 kg/m2 to 31.9 +/- 6.1 kg/m2 stopped with staple-line dehiscence, and all 46 patients regained weight, even to their original weight. After operative revision by restapling (n = 24/46) or implantation of an adjustable band (n = 10/46), patients reduced their body weight once more (to BMI 31.2 +/- 5.9 or 33.8 +/- 5.8)., Conclusion: Obese patients need the food-intake reducing operations maintained lifelong; the real cause of obesity is not curable until now, and only the main symptom, "overweight," can be improved by therapy.

Perinatal hypoxia is known as a high risk factor for the development of long-lasting abnormalities in dopaminergic system. The early developmental alterations of dopamine (DA) metabolism induced by hypoxia could contribute to these abnormalities. To understand the hypoxia-induced changes of intra- and extracellular dopamine levels and its main metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in immature dopaminergic neurons, we compared these changes in rat mesencephalic and diencephalic cell cultures on day in vitro (DIV) 2 (immature cells), DIV 8 and DIV 13 (mature cells). Cell cultures were exposed to an oxygen-free gas mixture in a Billups chamber for 2-4 hours. Mature cell cultures responded to hypoxia with an increase of DA levels in the cells and in the medium during the first 45 min (by an average of 57 and 114% respectively). Thereafter, DA levels decreased, and returned to the baseline within the next 30 min. The cellular DA levels continued to decrease up to 15% of the baseline during 255 min hypoxia whereas the extracellular DA content stabilized at the prehypoxic levels. Immature cell cultures (DIV 2) in contrast to mature ones, were unable to maintain normal extracellular DA levels during hypoxia and showed a decrease of the cellular and extracellular levels to 50% of the prehypoxic levels. DOPAC and HVA changes mimick, however, at a lower level, the pattern of DA changes during the exposure to hypoxia. In principle, in the diencephalic cell culture similar effects of hypoxia exposure on the investigated parameters were found (studied during 0-120 min). The present study demonstrates that mature and immature dopaminergic cells differ in the regulation of the extra- and intracellular DA levels during hypoxia. In immature cells the low synthetic capacity of tyrosine hydroxylase and the deficient capacities of the transport and storage processes result in decreased extracellular DA levels. This could be an important factor for the long-term modulation of the expression of tyrosine hydroxylase and subsequent long-term behavioral and/or neurological abnormalities induced by perinatal hypoxia.

The present study was conducted to elucidate the long-term effects of exposure to hypoxia of dopaminergic neurons during the early developmental period. Primary mesencephalic cell cultures prepared from fetal rats and containing 0.5-2% of dopaminergic neurons were exposed to hypoxia between in vitro days 1 and 6, the putative critical developmental period. Changes in the content, release and uptake of dopamine were found to depend on the degree of hypoxia and on the duration of exposure. Following moderate hypoxia (7 h, 5% O2) on two consecutive days between in vitro days 1 and 3, the cultures showed a small increase in the dopamine levels, by 16%. After severe hypoxia (0% O2/95% N2 for 24 h), during the same time window, the cellular dopamine content was elevated by 100%. Moreover, severe hypoxia produced long-lasting modulations of the dopaminergic system. On in vitro day 14, cells exhibited increased levels of 3,4-dihydroxyphenylacetic acid and homovanillic acid (by 34% and 55%, respectively), and elevations of both the spontaneous and potassium-stimulated dopamine release by 70%. The dopamine transport and metabolism of cells exposed to hypoxia between in vitro days 4 and 6 remained unchanged with regard to long-term effects. The present study provides strong evidence for the induction of long-term changes in dopaminergic cells due to hypoxia during the critical developmental period in mesencephalic culture. The developmental period capable of inducing long-lasting changes in dopamine metabolism is restricted to in vitro days 1-3.

The surgical treatment of morbid obesity by VBG or adjustable gastric banding techniques is very effective as 633 own patients demonstrate clearly. A significant weight reduction is possible in 75 to 80% of all operated patients. The BMI can be reduced from an original value of 49 kg/m2 to 33 kg/m2. An absolute necessity is a lifelong medical care of the patients, because long term complications may occur. The surgical treatment is believed to be an important help for the obese patients but not an easy solution of every problem of the obese.

The VBG enables a significant weight loss from an initial weight of 138.9 kg (mean value, n = 387) to 87.3 kg after 36 months. BMI is reduced from 48.9 to 30.8 kg/m2. Even the pathological metabolic disorders are improved like the rate of metabolic syndrome (8.4% to 2.2%). The postoperative complication rate is low with a letality of 0.26% or a thrombosis rate of 1,03%. The relative high rate of patients with ineffective weight loss (30-40%) should not lead to the consequence to stop the procedure, but to improve the pre-operative screening.

Objective: To evaluate the long term value of gastric bypass and horizontal gastroplasty for the treatment of morbid obesity., Design: Retrospective study., Setting: University hospital., Subjects: 119 patients of 195 who were operated on between 1976 and 1986., Interventions: Horizontal gastroplasty (n = 15), transected gastric bypass (n = 83), or stapled gastric bypass (n = 21)., Main Outcome Measures: Weight loss, reduction in body mass index, and morbidity., Results: Mean (SD) body weight (kg) after gastroplasty decreased from 139 (20) to 112 (14) at one year, but had increased to 130 (22) at 10 years. The corresponding figures for transected gastric bypass were 134 (24), 95 (20), and 103 (22); and for stapled gastric bypass 137 (27), 100 (24), and 112 (23). The figures for body mass index showed a similar pattern. Three quarters of the patients developed physical or psychological complications after the operation that were related to either the obesity or the operation, or both., Conclusions: None of the three operations provided adequate or prolonged control of morbid obesity, and the morbidity was high. Too large a proximal pouch, or disruption of the line of staples, may have been responsible.

In an experiment with Wistar rats the question of whether oral vitamin C application has a protective effect in liver carcinogenesis caused by N-nitrosodiethylamine in drinking water (n = 104) was studied. When comparing four groups (without carcinogen, with carcinogen and carcinogen plus vitamin C alternately and concomitantly) significant statistical differences in the linear regression were noted. Ninety per cent of the rats developed hepatocellular carcinomas when only carcinogen was administered whereas the rate with additional administration of vitamin C alternately and concomitantly was 68% and 55%, respectively. Without carcinogen no tumour developed. The results suggest that vitamin C may delay the development of liver cancer upon oral administration of N-nitrosodiethylamine. The explanation for this fact is still hypothetical.

In animal experiments with Wistar rats we attempted to determine if oral application of Vitamin C inhibits or delays carcinogenesis due to oral administered N-Nitrosopiperidine (NTP). One group of animals received NTP only, two other groups NTP and Vitamin C either alternating or simultaneously. A fourth group receiving only Vitamin C served as control. Carcinomas of the esophagus, stomach and liver developed in response to NTP application. The additional administration of Vitamin C neither inhibited nor delayed the development of carcinomas.

Inadvertent perforation or incision into rectal carcinoma during surgery may lead to massive dissemination of tumor cells in the operative area. It was observed in 8.7 percent of 1360 radical resections for cure. In time, the incidence could be reduced from 11.0 to 5.2 percent. Intraoperative spillage of tumor cells influences the incidence of local recurrence. In the last period (1982 to 1985) in cases of spillage of tumor cells, local recurrence was seen in 39 percent as opposed to 12.9 percent in perforation or incision of the tumor. Intraoperative tumor-cell spillage has a negative effect on survival rates, reducing the relative five-year survival rate after resection for cure from 70 to 44 percent. It should be recorded in the surgical and pathologic reports and considered in the analysis of treatment results and in selection of patients for adjuvant radiotherapy.

Thirty-two patients with segmental liver resection were fed 3 different parenteral infusion programs postoperatively. These differed in carbohydrate and lipid content, with the latter representing up to 40% of the total caloric content. Laboratory parameters, including nitrogen balance, acute phase proteins and liver function tests, were found to have a postoperative course similar to that seen following other major abdominal procedures. A transient rise of bilirubin observed may be related to the temporary decrease in the excretory function of the liver. The rise in acute phase proteins, beginning a few days postoperatively, was attributed to the ability of the remaining liver parenchyma to synthesize protein. There was no significant difference observed between the 3 parenteral solutions. Finally, we conclude that in the early postoperative period lipid solutions can be used as an important source of energy.

The Erlangen magnetic ring for colostomy closure was used in 240 patients. Forty-five rings were explanted because of infection, pressure necrosis, parastomal hernia, invagination, prolapse and stenosis. Although continence was obtained in 68% of patients, only 43% of surviving patients are still using the system. Reasons given for not using the cap were pain and weight. Increased use of deep anterior resections and the introduction of irrigation and improved stoma bags have limited the indications for the use of the magnetic ring.

In regard to other intestinal malignomas colon cancer shows the chance of a long survival time. In cases of stage Dukes A and B the patient has a 5 year survival time of 100 to 82% depending on his age. In carcinoma of the rectum preoperative biopsy is necessary. In cases with grade III we prefer the exstirpation. The Erlangen magnetic closure of the colostomy gives continence in 70%.

154 patients out of 317, who had undergone the Converse type of otoplasty in the ENT Department at Göttingen University, were assessed. Both subjective results and objective findings showed a successful operative outcome. Retractions of the concha were seldom seen and revision surgery was only necessary in 2 patients.

Incidence and distribution of lymph node metastases were examined in 100 gastrectomy specimens with 104 primary gastric carcinomas. Special emphasis was placed on the correlation with the location of the tumor and its size as well as the depth of infiltration and the tumor histology. Sixty-one percent of carcinomas with a diameter of up to 6 cm had lymph node metastases while this was the case in 83% of larger tumors. Infiltration of the muscularis propria only was associated with a 23% incidence of lymphogeneous metastases. This figure rose to 75% if the tumor reached the subserosa. Carcinomas of the diffuse (Lauren) or infiltrating (Ming) type show metastases more frequently (83% and 81% respectively) than those of the intestinal or expansive type (58%). In addition, several regions of lymphatic drainage are more frequently involved with the diffuse type. In only 2 patients (2% of all patients or 3% of the patients with lymphogeneous metastases) skipping of lymph nodes could be observed. In all other patients distant lymph nodes showed metastases only if the perigastric nodes next to the tumor were involved also. These findings support a differentiated, stage- and histology-dependent surgery.

The prognosis of gastric carcinoma is particularly unfavorable. 58% of 966 patients could be resected at the time of diagnosis, only 25% radically. The absolute 5-year survival rate is 18%, the 10-year survival rate 12%. After a curative resection 43% survive 5 years and 28%, 10 years. "A priori" gastrectomy showed no advantage in our patients. Therefore we prefer resection adapted to stage and grade for gastric cancer.

At the Surgical Clinic of the University Erlanten-Nürnber 61 per cent of the carcinoma of the oesophagus, 57 per cent of malignant tumors of the stomach and 28 per cent of all tumors of the large bowel and the rectum could not be operated radically. If there are no metastases in other organs or a wide-spread peritoneal dissemination a palliative procedure is advisable. Resection of the tumor itself has been the most effectful prodedure in cases of palliative treatment. Gastrostomies, bypass-anastomoses and protheses have been comparatively less successful. Radiation is indicated only in cases of squamoun cell-carcinoma of the oesophagus. In cases of the carcinoma of the rectum located in the middle and lower part causing a severe stenosis coagulation is an effective treatment.

The experimental series by dogs and pigs show no specific absorption place in the small intestine--except the high selective absorption of vitamin B12 in the last ileum loop. Potassium absorption is better in the upper jejunum. For all other substances the conditions for absorption are the same in the jejunum as in the ileum. Calcium, carotin and cholesterol need a sufficiently extensive surface and show therefore a direct relation to the length of the small intestine. For the treatment of the extreme obesity we perform the jejunoileostomy with different lengths of jejunum and ileum. The hypercholesterinaemia type II can be treated by a partial ileum bypass. By the diminished absorption of the bile salts a sufficient decrease of the cholesterol level is possible, which amounts to about half the earlier value. The jejunoileostomy reduces not only overweight, but also improves the carbohydrate metabolism and lowers the increased fat levels.

Squamous epithelium carcinoma of the esophagus occurs seldom in the Federal Republic of Germany and is not usually discovered until it is in an advanced stage. Surgical therapy is full of complications due to the high rate of accompanying illnesses. In the last few years the results could be considerably improved by the use of the stomach as a substitute organ. In spite of this, the five-year survival rate of 5-12% is extremely unfavourable.

From 1977 to 1984 esophageal resection and reconstruction by stomach due to squamous cell cancer of the esophagus was carried out by an abdomino-thoracic approach in 53 (A) and through a left-transthoracic approach in 57 (B) patients. Localisation and safety margins were practically identical: median orally A = 24, B = 29 mm, aborally A = 71, B = 49 mm. The overall lethality is significantly different: A = 41.5%, B = 22.8%. Without preoperative radiation or chemotherapy the mortality reaches in group A 39.5% and B 19.0%. Leakage rate in both groups is still high (A = 20.8%, B = 8.8%). However, the lethal respiratory insufficiency rate dropped from 15% (A) to 5% (B).

The special problems involving the histopathology of verrucous carcinoma of the esophagus are presented on the basis of two patients with this tumor seen at our department. The discussion centers on the question whether a verrucous carcinoma of the esophagus can infiltrate the basal membrane and give rise to metastases.

In 27 dogs esophagogastric anastomoses were performed in a single-layered end-on, a three-layered end-on and a double-layered inverting technique. The anastomoses were reinvestigated on the 2., 4., 7., 15. and 30. postoperative day. Suture line leakages were not observed. The inverted suture resulted in considerable anastomotic stenosis, ulceration of the mucosa, disordered and initially incomplete revascularisation, and widespread granulomatous inflammatory reaction. In contrast, the end-on technique led to almost no stenosis, ordered revascularisation, and narrow and delicate scar tissue formation while maintaining a normally layered structure. The single-layered methode was superior to the three-layered one. The best results were obtained by the extramucous technique.

Gastric bypass is an effective surgical procedure in the treatment of extreme obesity. A small gastric reservoir and a narrow anastomosis are combined to limit food intake. In patients with a mean weight of 94% above the Broca value, the normal weight is reached within 18 months after the operation. Failure to lose weight can be caused by technical errors during operation or by a continuous food intake after operation. Surgical complications are rare. The operative mortality is less than 1% and anastomotic ulcers occur in only 2% of cases. Unlike jejunoileal bypass, it causes no metabolic dysfunction.

In animal experiments (20 mongrel dogs) malabsorption was induced by resection of 100 cm ileum. Subsequently the influence of the ileocoecal valve (Valvula Bauhini) in absorption was studied. In one group of animals intestinal continuity was reestablished by ileoileostomy, in a second by ileocolostomy. The results of the absorption studies were compared with a healthy control group. After ileoileostomy animals do not lose weight, serum cholesterol and protein remain normal. Oral tolerance tests with Triolein-iodine-131 and Cyanocobalamine show results identical with those of the control group. After ileocolostomy all these parameters are lowered--partially to a pathological level. It is concluded that in all operations in the area of the terminal ileum and colon the Valvula Bauhini should be retained if possible.