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Gli3 is a key regulator of development, controlling multiple patterning steps. Here we report the generation of a scFv antibody specific to the repressor domain of human Gli3. We show that this scFv retains the binding capacity of its parent anti-Gli3 monoclonal antibody derived from hybridoma clone 5E1. When expressed in mammalian cells, the anti-Gli3 scFv co-localizes with intracellular Gli3. Immunocytochemical staining of the intrabody in Gli3-positive TM4 cells shows a distinct perinuclear cytoplasmic localization. Such a scFv constitutes a useful tool for studying transcriptional regulation of the hedgehog pathway in mammals and offers a starting point for developing novel Gli-related therapeutic intrabodies.

Losses of biodiversity and ecosystem functioning due to rainforest destruction and agricultural intensification are prime concerns for science and society alike. Potentially, ecosystems show nonlinear responses to land-use intensification that would open management options with limited ecological losses but satisfying economic gains. However, multidisciplinary studies to quantify ecological losses and socioeconomic tradeoffs under different management options are rare. Here, we evaluate opposing land use strategies in cacao agroforestry in Sulawesi, Indonesia, by using data on species richness of nine plant and animal taxa, six related ecosystem functions, and on socioeconomic drivers of agroforestry expansion. Expansion of cacao cultivation by 230% in the last two decades was triggered not only by economic market mechanisms, but also by rarely considered cultural factors. Transformation from near-primary forest to agroforestry had little effect on overall species richness, but reduced plant biomass and carbon storage by approximately 75% and species richness of forest-using species by approximately 60%. In contrast, increased land use intensity in cacao agroforestry, coupled with a reduction in shade tree cover from 80% to 40%, caused only minor quantitative changes in biodiversity and maintained high levels of ecosystem functioning while doubling farmers' net income. However, unshaded systems further increased income by approximately 40%, implying that current economic incentives and cultural preferences for new intensification practices put shaded systems at risk. We conclude that low-shade agroforestry provides the best available compromise between economic forces and ecological needs. Certification schemes for shade-grown crops may provide a market-based mechanism to slow down current intensification trends.

Stress-induced elevation of glucocorticoids is accompanied by structural changes and neuronal damage in certain brain areas. This includes reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus which can be prevented by chronic electroconvulsive seizures and antidepressant drug treatment. In the last years we have bred two strains of rats, one which reacts with congenital helplessness to stress (cLH), and one which congenitally does not acquire helplessness when stressed (cNLH). After being selectively bred for more than 40 generations these strains have lost their behavioural plasticity including their sensitivity to antidepressant treatment. We show here that in cLH rats, acute immobilization stress does not induce a reduction of BDNF expression in the hippocampus which is observed in Sprague--Dawley and cNLH rats. All animals tested exhibited elevated corticosterone levels when stressed, an indication, that in cLH rats regulation of BDNF expression in the hippocampal formation is uncoupled from corticosterone increase induced through stress. This may explain the lack of adaptive responses in this strain.

Autoantibodies to CRP were reported previously in patients suffering from toxic oil syndrome. This syndrome resembles autoimmune diseases such as systemic lupus erythematosus (SLE) or systemic scleroderma. We therefore examined the prevalence of antibodies to CRP and other acute-phase proteins in autoimmune diseases, including SLE, subacute cutaneous lupus erythematosus (SCLE), systemic scleroderma (SSc), and primary biliary cirrhosis (PBC), as well as in bone marrow transplantation-induced chronic graft-versus-host disease and eosinophilia-myalgia syndrome. IgG antibodies to CRP were found in 78% of SLE and in 30% of SCLE patients, while 16% of patients with PBC were positive. In up to 45% of patients with SSc predominantly IgG antibodies to ceruloplasmin were detectable. Lack of systemic involvement as in discoid lupus erythematosus and localized scleroderma (morphea) correlated with low or absent antibody formation. However, no correlation was found between anti-acute-phase protein antibodies with liver disease or other organ involvement. Adsorption studies revealed that non-native epitopes on the CRP molecule, termed modified CRP, are the main target of antibodies. Chronic inflammatory tissue injury in systemic autoimmune disease might increase the presentation of cryptic epitopes of CRP to the threshold required for T cell activation.

Background: Current therapies for recalcitrant psoriasis focus on immunoregulation and targeting of activated T-lymphocytes rather than keratinocytes. Previous studies with low doses of the lymphocyte-selective fusion protein DAB389IL-2 have shown benefit to patients with psoriasis., Objective: We examined the safety and efficacy of DAB389IL-2 in 41 volunteers receiving more frequent and higher doses than in a previous trial., Methods: Patients were randomized to receive either placebo or 5, 10, or 15 microg/kg daily of DAB389IL-2 intravenously for 3 consecutive days each week for 4 consecutive weeks with a subsequent 4-week observation period., Results: Of the placebo group, 17% (2 of 12) exhibited at least 50% improvement from baseline Psoriasis Area and Severity Index scores at the end of the study, whereas 24% of all treated patients (7 of 29) showed the same improvement. Overall, 3 of 12 (25%) patients given placebo as opposed to 12 of 29 (41%) patients treated with DAB389IL-2 improved to this same extent at some point during the study. The rate of improvement for treated patients was significantly greater than for placebo patients (p = 0.04; repeated measures ANOVA). Among treated patients, decreases in Psoriasis Area and Severity Index scores were paralleled by changes in the Physician's Global Assessment and the Dermatology Life Quality Index. Treatment in ten patients was discontinued because of adverse events. Flu-like symptoms were the most common with severity increasing at the two higher doses. Only one serious adverse event was reported. This occurred in a patient receiving 5 microg/kg daily who experienced vasospasm and a coagulopathy resulting in arterial thrombosis., Conclusion: Our findings are consistent with the potential antipsoriatic activity of DAB389IL-2 demonstrated in an earlier study. However, DAB389IL-2 was less well tolerated at this dosing regimen, particularly at the highest dose, and it was too toxic at these doses and schedules to be considered in the routine treatment of psoriasis.

In patients with insulin-dependent diabetes mellitus (IDDM) angiotensin-converting enzyme inhibitors (ACEI) have been demonstrated to have beneficial effects in the secondary prevention of microvascular complications. There are only few data available regarding the effect of ACEI on microcirculation in patients with IDDM without any microvascular complications. In addition, there is little knowledge about ACEI action during acute hyperglycemia. In a pilot study nine patients with IDDM without any clinical signs of diabetic complications (5 females, 4 males, aged 33.3 +/- 1.0 years, duration of diabetes 11.4 +/- 3.0 years, HbA1 7.2 +/- 0.2% [normal range 4.8-7.4%], BMI 21.4 +/- 0.5 [kg/m2]) received 1.25 mg of the ACEI ramipril (Delix, Hoechst Marion Roussel, Frankfurt) over 4 weeks. Nine healthy volunteers (4 females, 5 males, age 27.4 +/- 1.1 years, HbA1 5.9 +/- 0.2% (p < 0.01 vs patients), BMI 22.2 +/- 0.9 [kg/m2]) served as controls. Using nailfold capillaroscopy we determined capillary blood cell velocity (CapiFlow, Lawrenz Electronics, Sulzbach, Germany) before and during post-occlusive hyperemia (200 mmHg for 3 minutes) as a provocative test. Before and after treatment patients were studied during hyperglycemia (blood glucose 250-350 mg/dl). Treatment with low-dose ramipril resulted in a significant decrease in the time to peak capillary blood cell velocity during post-occlusive hyperemia (17.8 +/- 7.7 vs 57.4 +/- 12.8 s, p < 0.01) in hyperglycemic patients. This effect was absent in healthy volunteers. Hemodynamic and metabolic parameters remained unchanged throughout the study in both groups. These data demonstrate that low-dose therapy with the ACEI ramipril is able to improve microcirculation in hyperglycemic patients with type 1 diabetes mellitus also before microvascular complications are evident. Prospective studies are necessary to evaluate whether this effect might be clinically relevant in the primary prevention of diabetic microangiopathy.

Background/methods: The two envelope proteins of hepatitis C virus, E1 and E2, were expressed in E. coli and, as secretory proteins, in Sf9 insect cells using recombinant baculoviruses. Co-infection of insect cells with E1 and E2-recombinant baculoviruses was performed, which has been shown to result in formation of E1-E2 dimers. All envelope proteins were purified by Ni2+-NTA chromatography and used for screening of serum samples in a HCV EIA assay. Serum samples of normal blood donors, chronically HCV-infected patients, a mixed titer panel and several seroconversion panels were screened and compared to test results with Cobas Core Anti-HCV EIA., Results: Screening of the sera of chronically HCV-infected patients (100% positive in Cobas Core Anti-HCV EIA) revealed 10-40% anti-E1 positive sera using different Sf9-expressed, glycosylated proteins and 93% using E. coli-expressed, non-glycosylated E1 protein. When the same sera were tested with different E2 proteins expressed in Sf9 cells and in E. coli, about 70-73% showed anti-E2 reactivity. When the proteins from Sf9 cells co-infected with E1- and E2-recombinant baculoviruses were tested, 70-80% of the same sera showed anti-envelope reactivity., Conclusions: Testing of these patient antisera, and those from the well-characterized mixed titer panel BBI-PHV203, showed that recombinant E1 expressed in E. coli and co-expressed E1 and E2 proteins from Sf9 cells could be used as additional tools for anti-HCV antibody screening.

Molluscum contagiosum virus (MCV) is a common pathogen causing a troublesome skin condition in many immunocompetent individuals and a widespread, disfiguring affliction in many patients with AIDS. We have successfully infected human foreskin fragments with a patient-derived isolate of MCV. This was demonstrated by exposing the foreskin pieces to a patient lesion extract and implanting the tissue under the renal capsule of athymic mice. Light and electron microscopic examination of infected implants showed the presence of cytoplasmic inclusions containing typical poxvirus particles within 2-3 weeks of implantation. Replication of MCV was established by demonstrating that viable virus was required to produce the cytopathologic effects, and viral DNA replication was demonstrated by incorporation of bromodeoxyuridine into cytoplasmic inclusions. Four additional patient extracts (representing both described MCV types) were also used to successfully infect foreskin implants. A limited number of attempts to pass virus from one infected implant to another were not successful. This system is the most rapid and reproducible for growing MCV that has been reported to date.

Considerable interest has been recently generated concerning the use of natural compounds, anti-oxidants in particular, in photoprotection. Two of the best known anti-oxidants are vitamins C and E, both of which have been shown to be somewhat effective in different models of photodamage. Very little has been reported, however, on the effectiveness of a combination of the two (known to be biologically the more relevant situation); nor have there been detailed studies on the ability of these antioxidants to augment commercial sunscreen protection against UV damage. We report that (in swine skin) vitamin C is capable of additive protection against acute UVB damage (sunburn cell formation) when combined with a UVB sunscreen. A combination of both vitamins E and C provided very good protection from a UVB insult, the bulk of the protection attributable to vitamin E. However, vitamin C is significantly better than vitamin E at protecting against a UVA-mediated phototoxic insult in this animal model, while the combination is only slightly more effective than vitamin C alone. When vitamin C or a combination of vitamin C and E is formulated with a commercial UVA sunscreen (oxybenzone), an apparently greater than additive protection is noted against the phototoxic damage. These results confirm the utility of anti-oxidants as photoprotectants but suggest the importance of combining the compounds with known sunscreens to maximize photoprotection.

Chronic graft-versus-host disease after bone marrow transplantation presents, in a few cases, as mild to severe scleroderma-like changes. Patients with chronic graft-versus-host disease with and without sclerodermatous skin changes were analysed for antinuclear autoantibodies (ANA) and antinucleolar autoantibodies (ANoA) and the results correlated with disease symptoms and histocompatibility locus antigen (HLA) pattern. Nineteen patients with chronic graft-versus-host disease and scleroderma-like skin changes, 18 with chronic graft-versus-host disease without scleroderma, and 17 controls on immunosuppressive treatment were screened for ANA and ANoA using enzyme-linked immunosorbent assay, immunodiffusion and immunoblot techniques. Four patients with severe scleroderma had antibodies to topoisomerase I, two had antibodies against PM-Scl, both characteristic serological findings in idiopathic systemic scleroderma. One patient had La/SSB antibodies and, in three cases, antibodies to the nucleolar antigen C23 (nucleolin) could be identified. A possible correlation between antinucleolin antibodies and disease activity was observed. HLA-A1, -B1, and -B2 were found significantly more often in patients with scleroderma-like symptoms in comparison to patients without scleroderma-like symptoms. Chronic graft-versus-host disease with scleroderma-like manifestations can be associated with the occurrence of ANA specific for idiopathic scleroderma. The development of scleroderma after bone marrow transplantation might have a HLA-linked genetic background.

The operative technique of endoscopic extraperitoneal inguinal and femoral hernia repair without fixation of the polypropylene patch is presented. The results of 725 inguinal and femoral hernia repairs are demonstrated and discussed.

The technique of laparoscopic sigma-/rectum-resection and the technique of the laparoscopic abdominoperineal excision of the rectum are discussed under oncological aspects. The results of 24 laparoscopic resections of sigma and rectum and of 15 laparoscopic abdominoperineal excisions of the rectum are demonstrated.

Sympathetic skin response (SSR) was investigated in 60 normal subjects (mean age 37.7 +/- 15.9) and 30 patients (mean age 47.2 +/- 12.0) referred from the department of urology for further electrophysiological evaluation of erectile dysfunction (ED). SSR was present in all normal subjects. Mean latency in the lower extremities was 2.16 +/- 0.20 sec. The coefficient of variance for repeated measurements in individual subjects was 10%. The latencies correlated slightly positively with the height of the subjects (r = 0.271, p < 0.05), but not with age. SSR in patients was compared to the bulbocavernosus reflex (BCR) and somatosensory evoked potentials (SSEP) of the pudendal nerve. All patients had a complete urological work-up with evaluation of hormonal function, pharmacotesting and Dopplersonography, as well as pharmacocavernosography and measurement of nocturnal penile tumescence if indicated. Six patients were diagnosed to have functional impotence, 4 dysfunctions were probably of vascular origin, 5 were neurogenic and 15 of the mixed type of vascular and neurogenic origin. Diabetes mellitus was the underlying disease in 14. In the two groups with neurogenic involvement (5 neurogen, 15 mixed) 14 of 20 patients had a pathological BCR, 12 had pathological SSEP and 9 had an absent SSR. Of these 9 patients two showed normal BCR and SSEP. Sensitivity for neurogenic dysfunction was 70% for the BCR, 60% for the BCR and SSEP, but that it detects some patients with erectile dysfunction, in whom other parameters are not pathological.(ABSTRACT TRUNCATED AT 250 WORDS)

As a result of 1277 laparoscopic cholecystectomies, which were performed as a standard procedure in uncomplicated and complicated symptomatic cholecystolithiasis, the complication-rates of conventional cholecystectomy and laparoscopic cholecystectomy are compared. It can be demonstrated, that the adoption of the principles of conventional cholecystectomy into laparoscopic technique and a careful preparation can reach the same high level of safety as the so called "gold-standard".

Sympathetic skin reflex (SSR) was evaluated in the lower extremities of 60 normal volunteers aged 17 to 72 (mean age 38 +/- 16 years, 28 females, 32 males). SSR was obtainable in all volunteers and most often consisted of a biphasic wave with initial negative deflection. Mean latency was 2.16 +/- 0.20 s. Mean variation in a second repetitive measurement was 0.21 +/- 0.14 s. The SSR was not age- or sex dependent. There was a weak positive correlation of the SSR with the height of the volunteers (r = 0.271; p = 0.037). SSR was investigated in 39 patients with polyneuropathy (age 59 +/- 18). SSR was pathological in 51% on one or both legs. There was no correlation of the SSR to the aetiology nor to the type of lesion (axonal versus demyelinating polyneuropathy) nor to clinical symptoms. The applicability of the SSR is reviewed from the literature regarding polyneuropathy, erectile dysfunction, central degenerative diseases, multiple sclerosis, sympathetic reflex dystrophies, spinal and peripheral nerve lesions. SSR is briefly compared to alternative methods. SSR appears to be a reasonable method to describe a small section of the autonomic nervous system (sympathetic sudomotor function) and to calculate group differences. There appears to be no close correlation to any of the autonomic disturbances in individual patients.

The sympathetic skin response (SSR) was evaluated in 25 patients with amyotrophic lateral sclerosis (ALS) to assess for involvement of the autonomic nervous system. Twenty-two age-matched normals and 6 patients with muscular dystrophy served as controls. The SSR was intact in all normal volunteers and all patients with muscular dystrophy. The mean SSR latency in the ALS patients was prolonged compared to that of normals (2.29 +/- 0.28 versus 2.13 +/- 0.16 s, P < 0.05). The SSR was absent in one or both legs of 10 ALS patients (40%). Absence or abnormal latency of SSR in patients with ALS without clinical findings of autonomic failure suggests involvement of the autonomic nervous system in addition to the motor system.

This report describes a black woman with a history of cutaneous Mycobacterium kansasii responsive to antituberculous drugs. A culture several years later of cutaneous lesions was also positive for Histoplasma capsulatum. Both cutaneous diseases are rare and most often occur in immunocompromised hosts. There is no known association between these two diseases. This patient may have an as-yet unidentified immunodeficiency that predisposes her to these rare infections. Her case emphasizes the importance of repeat biopsy for atypical skin lesions.

In 7 convalescent patients we studied utilisation of a single dose of 15N-labelled glycine. In intervals we estimated total-N, urea-N, NH3-N and their 15N-abundances (urine). The following results were obtained. The peak of ammonium-15N appeared 25 minutes earlier than the peak of urea-15 N. The cumulative elimination of total-15N amounted to 25% of uptake after 24 hours and to 34.4% after 6 days. 12 hours after application 53% of the total amount, excreted within 6 days, were already eliminated. 24 hours after administration 80% of total-15N was urea-15N and 2.8% NH3-15N. Further we found correlations between N-balance (N-application minus excretion) and elimination of 15N-urea: If N-balance got more negative, the amount of cumulative elimination, the portion of urea-15N to total-15N and the percentage of elimination after 12 hours related to 6 days were elevated. That means that in stress condition utilisation of glycine to urea is higher and accelerated. The model seems acceptable, to get information concerning metabolic situation in a simple way.

Indication and significance of roentgenological procedures referring to esophageal and gastric motility are discussed with special reference to a number of functional disorders. Cinematography and tape-recording are necessary for fast peristaltic motion as in vascular, neurological and myogenic diseases of the upper esophageal sphincter. Pharmacological response may for instance help to differentiate functional from morphological disorders or postoperative complains. Combinations of roentgenological and radioisotopical studies or manometry may be usefull for special diagnostic problems.

Chloromethyl phthalimide, oxymethyl phthalimide, and phthalimide are absorbed by the albino rat at a comparatively high rate. Only phthalimide, the metabolic product, will be recordable from fetuses, following oral administration of chloromethyl phthalimide and oxymethyl phthalimide topregnant rats. Those findings, in conjunction with metabolic studies applied to fetuses isolated by caesarian section, appear to suggest the occurrence of an intensive metabolism in fetal tissue. Certain differences established between results of thin-layer chromatography, on the one hand, and 15N studies, on the other, are likely to support the assumption that phthalimide is further metabolised by splitting the imide ring yielding phthalamic acid.

Thirteen patients with metastatic squamous cell cancer of the lung were treated, in a nonrandomized study, with an oral high-dose methotrexate and citrovorum factor rescue regimen. There was some response and/or stabilization of disease for at least three months in six (46%) of 13 cases. The median survival time of the study group was double (365 vs. 180 days) that of a retrospectively matched control group. This suggests a possible therapeutic effect of this treatment program in metastatic squamous cell cancer of the lung.

A simple, noninvasive test is proposed to measure the activity of the hepatocellular monooxygenase system in vivo. Elimination rates of the stable isotope 15N are measured in urine after an oral dose of the 15N-labeled phenacetin homologue [15N]methacetin. Different forms of obtaining and expressing results are investigated in order to determine optimum methodology and differentiation for clinical application in pediatrics. The best discriminating power and reliability of results are seen with the measurement of 15N elimination half-life. For follow-up, a more easily measured parameter--eliminated dose over 9 h--is sufficient. In the latter case, only total nitrogen and 15N contents of a collective urine sample are measured.

The quality of esophageal voice and speech after laryngectomy depends on several factors. Negative influences are produced by irradiation, resection of the hyoid bone and radical neck dissection. The factors important in esophageal speech were analyzed, with consideration given to the functional morphology of the pseudoglottis and the reconstructed hypopharynx. Phoniatric, laryngologic and radiologic aspects are considered.

A standardized 15N tracer method is described for the assessment of the nitrogen and protein metabolism in healthy and pathological changed organism. The method represents an isotope technical procedure for the application in the clinical research and practice. The single parts of this routine method are: --the clinical preparation of the patient/proband by means of a standardized nutritional regime, --the tracer administration (single dose) and the sampling (urine, blood), --the 15N-tracer technique (sample chemistry, emissions-spectrometric isotope analysis), --the mathematical evaluation of 15N tracer data.

A simple, non-invasive, non-radioactive liver-function test is proposed. After an oral dose of 3 mg 15N-methacetin per kilogram body mass, the kinetics of 15N excretion via urine were characterized by the quotient of the amounts of 15N excreted in two successive urine samples (Q value). The stable nitrogen isotope 15N was found to be an excellent and easily detectable indicator of the sum of all methacetin metabolites present in urine. Alterations in the nature or ratio of methacetin metabolites due to liver diseases could not be found. From the investigation of 11 men, 3 pregnant women and 15 children, a clear difference was observed in Q values of healthy persons and patients suffering from liver-cell-activity diseases. The discriminating power of our new liver-function test is shown to be equivalent to that of the 14CO2 breath test.

The 'sump syndrome' is a rare, late complication of choledochoenterostomies. We observed 13 patients with this syndrome. The clinical features included recurrent cholangitis, liver abscesses, and recurrent pancreatitis. Five patients were treated by surgery, eight patients endoscopically. Reviewing an average follow up period of 22 months (range 6-60) after therapeutic endoscopy and 57 months (range 1-126) after different surgical procedures, we conclude that endoscopic sphincterotomy with removal of the debris is as efficient a therapy of the 'sump syndrome' as surgical sphincteroplasty and entails a smaller risk for the patient. We therefore advocate that endoscopic papillotomy should first be tried in all cases of 'sump syndrome' in the absence of suprapapillary stricture of the bile ducts.

The importance of 15N as tracer in medical research is increasing. Since 1965 many results were obtained in cooperation of surgeons (Surgical clinic of Karl-Marx-University; Bezirkskrankenhaus St. Georg, Leipzig) and coworkers of Central Institute of Isotope and Radiation research. Using 3 test models (15N-labelled amino acid solution, permanent infused; 15N-labelled glycine, given as one single dose; 15N-labelled casein, oral given) healthy persons, patients in stress condition and after gastric operations and rats after performing several types of gastric operations were studied. Possibilities of calculations with mathematical models are shown.

The case of a 30-year-old woman with intra- and extrahepatic biliary dilatations (Caroli's disease) is reported. The features of the disease and its differential diagnosis are discussed. Special reference is given to the diagnostic approach by endoscopic retrograde cholangiography and to treatment with Chenodeoxy-cholicacid.

Stable isotopes, such as 13C, should be substituted for the long-lived radionuclide 14C in the 14C breath test when doing liver function tests in children and pregnant women. For comparison 13C, 15N-methacetin and 14C-methacetin were synthesized as suitable diagnostic agents. Methods are described for the measurement of 14C and 13C in the breath. After oral administration of labelled methacetin to healthy subjects and patients with liver diseases a good correspondence between 13C- and 14C-measurements in the same subject on the one hand, and a good discrimination between controls and patients on the other hand were shown. Findings with regard to 14C measurements in urine are discussed supporting the supposed advantage of 13C-methacetin over 14C-methacetin application.

A new isotope method for the determination of the residual volume of the lungs by means of stable, non-radioactive nitrogen isotope 15N is described. Normal air is breathed in a closed system. One part of the air nitrogen is replaced by 15N labelled molecular nitrogen. 15N2 physiologically acts like normal nitrogen so that the so-called secondary effects by using He or H2 are eliminated. By combination of a spirograph and an emission spectrometric 15N analyser the residual volume can be determined and mixing curves can be obtained. The determination of the residual volume in 10 healthy persons gives a range of normal values from 19 to 31% of the total capacity. In three persons with emphysema values from 45 to 50% of the total capacity are found. The analysis of mixing curves leads to additional informations concerning the intrapulmonary gas mixing conditions in the lungs. The relative error of the residual volume determination is about 8%.

The results of endoscopic retrograde cholangio-pancreatography were evaluated in a prospective study of 126 patients in respect of diagnostic accuracy, as compared with surgery and clinical follow-up. The diagnosis was incorrect in 11 patients; in seven it failed to differentiate between acute and chronic pancreatitis. The discrepancies in the other four patients are described in detail, particularly with reference to prepapillary filling defects. The indications, advantages and limitations of ERCP are discussed.

Cannulation of the papilla has been successful in 144 out of 197 ERCPs. The rate of success increases with the experience of the endoscopist. The intended filling of the pancreatic duct was successful in 87%, of the bile ducts in 64% and of both duct systems in 28%. The correct diagnosis was made in 77% of pancreatic affections, 71% of biliary diseases and in 43% when both duct systems had to be evaluated. 10 ERCP findings disagreed with the final diagnosis, mainly because the distinction between acute and chronic pancreatitis was not correct. The differentiation of chronic pancreatitis from pancreatic carcinoma is not easy and the evaluation of processes localized to the papilla may be difficult. Complications occurred in 6.6%. It is concluded that the ERCP should be limited to regional hospital centers and should be performed only in cases with well defined indications.

This study compares the effect of two amino acid solutions on protein metabolism after injury by measuring nitrogen balance, 15N-elimination, total body protein synthesis and utilisation of administered nitrogen in an experimental study using pigs. Protein synthesis and nitrogen utilisation were determined using a 15N-tracer technique with recourse to mathematical model concepts. The non-surgical control animals had a lower urinary nitrogen excretion, a more favourable nitrogen balance, a higher 15N-retention, greater total body protein synthesis and utilisation of the infused amino acids during infusion of an amino acid solution with a standard amino acid pattern (A) than the operated animals (solution B). Comparison of the post-operative data shows that if solution A is compared with solution B whose amino acid content takes account of changes in plasma amino acid metabolism following trauma, solution B yields the better results in respect of 15N-retention as well as total body protein synthesis and nitrogen utilisation.

The 9th observation of esophageal intramural diverticulosis is reported. The findings are compared with those of former publications. Clinically dysphagia is a leading symptom. Suction biopsy proved diverticulosis being the correct interpretation for radiological findings. The etiology is discussed. The change between symptom-free intervals with diverticulosis only and episods of dysphagia by secondary inflammation (reflux esophagitis, moniliasis, stenosis) stresses the importance of such secondary complications. These inflammations can hide the real diagnosis for a long time. The radiological findings are the key for diagnosis, however, they can be very small for years. During this period a diagnosis can only be achieved by knowledge of the disease and the skilful search for early symptoms.

Malfunction of the liver involves disturbances of urea synthesis and ammonia detoxification. These phenomena became apparent, especially during ammonia loading of patients. The functional state of the liver can be assessed by oral administration of 15NH4Cl and subsequent analysis of 15N-urea and 15N-ammonia in urine by emission spectrometry. Clinical tests based on the ratio of the excess abundances of 15N-ammonia to 15N-urea excreted in urine 3 h after oral administration gave values for patients with liver disease which differed significantly from those for healthy subjects. Absorption disturbances, which often accompany liver diseases, do not influence the effectiveness of the method.

The functional state of the liver can be assessed by oral administration of 15N labelled ammonium chloride (tracer) and subsequent isotope analysis of [15N]urea and [15N]ammonia in urine. Clinical tests based on the ratio of the excess abundances of [15N]ammonia to [15N]urea excreted in urine 3 hours after oral administration of the tracer gave values for patients with liver diseases which differed significantly from these of healthy subjects.

1. Under stress an increased amount of labelled amino acids is incorporated. 2. Under the conditions of stress amino acids too participate in the process of synthesis. 15N-glycine was used as tracer in a quantity of 0.64 g of amino acid and 24 kcal per kg per day, that is at a 0.027 g per kcal. hour infusion rate, so that the infused 15N corresponded to 75% of the total residual nitrogen in healthy subjects and 57% in operated patients. 3. Sixteen percent of the infused 15N is secreted with the urine of healthy subjects as urine nitrogen, and 57% as urine nitrogen and 4--5% as ammonia nitrogen with the urine of the operated cases. 4. In contrast to normal conditions, under stress a higher percentage of the infused amino acids participates in energy production. 5. Stress enhances uropoiesis as in regards both quantity and speed. 6. No difference in acid-base balance was found in the case of postoperative infusion; urinary and plasma concentrations remained within normal limits.