TRANSFAC: transcriptional regulation, from patterns to profiles.

The TRANSFAC database on eukaryotic transcriptional regulation, comprising data on transcription factors, their target genes and regulatory binding sites, has been extended and further developed, both in number of entries and in the scope and structure of the collected data. Structured fields for expression patterns have been introduced for transcription factors from human and mouse, using the CYTOMER database on anatomical structures and developmental stages. The functionality of Match, a tool for matrix-based search of transcription factor binding sites, has been enhanced. For instance, the program now comes along with a number of tissue-(or state-)specific profiles and new profiles can be created and modified with Match Profiler. The GENE table was extended and gained in importance, containing amongst others links to LocusLink, RefSeq and OMIM now. Further, (direct) links between factor and target gene on one hand and between gene and encoded factor on the other hand were introduced. The TRANSFAC public release is available at http://www.gene-regulation.com. For yeast an additional release including the latest data was made available separately as TRANSFAC Saccharomyces Module (TSM) at http://transfac.gbf.de. For CYTOMER free download versions are available at http://www.biobase.de:8080/index.html.

[Diagnosis and therapy of anorectal diseases (excluding constipation and venereal diseases)]. / Diagnostik und Therapie anorektaler Erkrankungen (exklusive Obstipation und venerische Erkrankungen).

In the last couple of years, the anorectum has been of great interest to gastroenterologists. With new diagnostic tools and a refinement of technique, together with new therapeutic modalities, interesting research results have been obtained. These results may be beneficial to patients therapy. The patients history, inspection and palpation of the anorectum remain the basic, essential features of diagnosis. Based on the symptoms and possible differential diagnosis, further investigation is necessary: Anorectal physiology and anal endosonography are also regarded as essential investigative techniques in a colorectal laboratory. Great progress has been made in the medical treatment in proctology in two areas: Biofeedback techniques and botulinum toxin injection. In the following article, definitions, symptoms, diagnosis and therapeutic modalities of common anorectal disorders are described.

DIZE (dexamethasone, idarubicin, and continuous infusion of ifosfamide and etoposide): an effective and well-tolerated new regimen for patients with relapsed lymphoma.

We performed a phase II study of dexamethasone, ifosfamide, idarubicin and etoposide (DIZE) in patients with relapsed or refractory Hodgkin's (HL) and non-Hodgkin's lymphoma (NHL). The regimen consisted of dexamethasone (20 mg i.v. days 1-4), idarubicin (8 mg/m2 i.v. days 1+2), continuous infusion (c.i.) of ifosfamide (1,000 mg/m2 days 1-4), and c.i. etoposide (60 mg/m2 days 1-4). G-CSF (5 microg/kg) was used to support neutrophil recovery from day 5. In older patients (> 60 years) the dosage of idarubicin and ifosfamide was reduced to 75% in the initial cycle. Fourty six patients (pts) were treated with a total of 131 cycles. Sixteen pts were primary resistant and 30 were relapsed. Median age was 54.3 years (range 22-75). The median number of different prior chemotherapies was 1.7 (range 1 to 5). 31/46 (67.4%) pts had advanced disease (stage III or IV); 19/46 had B symptoms. Of 43 evaluable pts the response rate was 58.1% including 11 complete remissions (CR) and 14 partial remissions (PR). Mean duration of response was 8 months (1-30+). DIZE was more effective in relapsed than in refractory high-grade NHL (74 % vs 16.6%; p < 0.001). Of four heavily pretreated pts with HL, one obtained CR and two PR (response rate 75%). Myelosuppression was generally moderate with a mean duration of leukocytopenia < 1,000/microl of 2.5 days (range 0-18) and of thrombocytopenia < 25,000/microl 1.5 days (range 0-17). One patient died of uncontrollable infection in treatment related neutropenia. No other serious toxicities apart from alopecia were observed. We conclude that DIZE is safe and effective in heavily pretreated pts with relapsed lymphoma. The continuous infusion of cytostatic drugs such as that used in the new DIZE protocol might reduce hematotoxicity.

[Expedition, experiment and expertise reflected in Robert Koch's assets]. / Expedition, Experiment und Expertise im Spiegel des Nachlasses von Robert Koch.

Basic techniques in bacteriology provided the foundation for the success of experimental medicine. The combination of laboratory experiments and field studies consolidated bacteriology as a paradigm for the development of preventive strategies. Robert Koch's (1843-1910) contribution to this development is crucial in that he integrated the technical facilities of his era into microbiological research. The present study introduces various sources of Koch's assets which, in addition to manuscripts and letters, include also bacteriological slides and photographs. These relicts allow to reconstruct an example of the scientific process as a whole, to investigate his style and purpose as a scientist, and to follow Koch's strategy of visualisation with contemporary technical equipment. The example chosen is Koch's last expedition when the German government sent him to investigate the spreading of sleeping-sickness in Eastern Africa and to test "Atoxyl" as a specific remedy. Most case-studies and laboratory-research took place on the Sese-Islands in Lake Victoria and illustrate the extreme conditions in tropical Africa. The experiments searching for the etiological agent of sleeping-sickness--a typical disease only for central Africa--involved bacteriological slides which were to be the basis for further experimental results and the expertise expected of him.

Faecal immunoreactive lipase: a simple diagnostic test for cystic fibrosis.

UNLABELLED: The study evaluates faecal immunoreactive lipase (IRL) measurement in spot stool samples as an index of exocrine pancreatic function in patients with cystic fibrosis (CF). Stool samples (211) from 183 healthy volunteers (age range: 2 days-14.2 years) showed a normal log distribution of IRL values with a median concentration of 71.4 micrograms/g (range: 0.53-4160 micrograms/g). In 156 stool samples from 58 patients with proven CF, the median IRL concentration of 0.4 microgram/g (range: 0.003-107 micrograms/g) was significantly lower (P < 0.001) than that of normal controls. In healthy controls, IRL levels were age related with significantly higher levels (P < 0.001) shortly after birth compared to older children. Stimulation of the exocrine pancreas by oral milk feeding resulted in a significant (P < 0.001) increase in a faecal IRL concentration. Faecal IRL concentrations in meconium were very low and of the same magnitude as in patients with CF. CONCLUSION: Faecal IRL determination had a high diagnostic sensitivity (87%) and excellent diagnostic specificity (97%) in patients with CF. A negative test result (PVneg. 99%) virtually excluded CF under screening conditions.

[Experiences with a computer-assisted concept for patient education in gastroenterologic endoscopy]. / Erfahrungen mit einem computergestützten Konzept zur Patienteninformation in der gastroenterologischen Endoskopie.

The purpose of this study was the assessment of the effect of audio-visual information, based on computer technology, on the reduction of anxiety in patients referred for gastrointestinal endoscopies. 72 of 100 consecutive patients (38 females, 34 males; median age 49 years [13-80 years]) were willing to study the available computer program for pre-diagnostic information. They were questioned regarding their anxiety about the forthcoming examination, and the acceptance and handling of the computer system. Anxiety levels were measured by a Visual Analogue Scale directly before endoscopy and after the examination. Nearly two thirds of the patients (60%) stated, that their anxiety level was reduced by watching the computer program. 96% of the patients felt comfortable with this type of information. Thus, the pre-procedure information demonstrated by the computer (backgrounds, instruments and procedural technics) relieves in a surprisingly large percentage of patients fears and worries about endoscopic procedures.

[Intestinal diseases in HIV infection]. / Darmerkrankungen bei HIV-Infektion.

The gastrointestinal tract is very frequently affected by the manifestations of the acquired immunodeficiency syndrome (AIDS). A variety of opportunistic viral, fungal, bacterial, protozoal and helmintic infections and different unusual malignancies such as Kaposi's sarcoma, non-Hodgkin's lymphoma and papilloma-virus associated anal cancer are responsible for much of the morbidity and mortality in AIDS. Because specific therapy is not always available, in particular diagnosis of potentially infections should be attempted.

Long-term follow-up after treatment of common bile duct stones by extracorporeal shock-wave lithotripsy.

BACKGROUND AND STUDY AIMS: The efficacy of extracorporeal shock-wave lithotripsy (ESWL) of difficult bile duct stones that were not amenable to routine endoscopic extraction was assessed, with evaluation of the long-term follow-up after successful treatment. PATIENTS AND METHODS: Fifty-four patients (mean age 74 years, range 33-92) were treated with ESWL for difficult bile duct stones. Treatment was performed either with the Dornier HM3 kidney lithotriptor (49 patients) or with the MPL 9000 lithotriptor (five patients). RESULTS: Stone disintegration was achieved in 50 patients (93%), with complete stone clearance in 45 patients (83%) (mean 1.2 session). Patients with successful stone removal after one session had significantly smaller stones than patients with treatment failure (20 +/- 9 versus 27 +/- 8 mm; p < 0.05). An intrahepatic location of stones was significantly associated with treatment failure (p < 0.005). Serve complications occurred in 7% (procedure-related 5%), with a 30-day mortality rate of 0% (in-hospital mortality rate of 2%). Minor side effects such as fever, petechiae, and mild arrhythmias were frequent (37%), and microhematuria (95%) occurred in nearly all of the patients. Symptomatic recurrent bile duct stones were observed in two patients (5%) after three and four years, respectively (mean follow-up 5.3 years). CONCLUSION: Extracorporeal shock wave lithotripsy represents a safe and effective treatment modality for difficult bile duct stones, with a low rate of symptomatic recurrences.

Indirect parameters of pancreatic function in cystic fibrosis (CF) during a controlled double-blind trial of pancreatic supplementation.

During two treatment periods (4 weeks each), serum immunoreactive trypsin (IRT), immunoreactive human lipase in stool (IRL), and chymotrypsin (CT) activity in stool were determined in 16 cystic fibrosis patients and compared with fecal fat excretion (72-h sampling). Fecal fat estimation revealed mild to severe steatorrhea in all 16 patients (X = 13.7 +/- 9.0 g/24 h) in at least one study period. Stool fat excretion was highest in underweight adolescents and adults. Comparison of IRT and IRL with stool fat values showed no significant statistical correlation. IRT values revealed an inverse exponential correlation with age, with a steep decline at the age of 5 years. CT levels were very high in 14 of our 16 patients during supplementation therapy, whereas 2 patients showed subnormal CT values. We conclude that since indirect parameters of pancreatic function do not correlate with stool fat excretion, stool fat remains the best indirect parameter for the assessment of pancreatic insufficiency in cystic fibrosis. Leaving pancreatic enzyme supplementation in cystic fibrosis patients on the basis of normal serum trypsin or fecal lipase values does not appear to be adequate.

[Results and risks of needle papillotomy]. / Ergebnisse und Risiken der Nadel-Papillotomie.

Needle knife papillotomy is an effective endoscopic procedure by which endoscopic sphincterotomy can be performed when conventional techniques have failed. We performed 35 (25%) pre-cut papillotomies, out of 142 therapeutic sphincterotomies, to enhance the cannulation of the bile duct in order to complete endoscopic sphincterotomy using standard techniques. In 30/35 patients pre-cut alone was sufficient to cannulate the duct, while in 4 of the remaining 5 patients a further ERCP after 2-8 days after the initial pre-cut was necessary to complete sphincterotomy. Only 4 episodes of bleeding were observed. One patient required transfusion of two units of blood. In our opinion needle knife papillotomy is a safe procedure for increasing the cannulation rate of the bile duct, and thus allow endoscopic sphincterotomy to be performed when conventional technique fails.

[A trial of modified triple therapy for the eradication of H. pylori in recurrent duodenal ulcer]. / Versuch einer modifizierten Tripeltherapie zur H.-pylori-Eradikation bei rezidivierendem Ulcus duodeni.

In a prospective trial we examined the efficacy and acceptability of a modified triple therapy in H. pylori (HP)-positive patients with recurrent duodenal ulcer disease. Oral administration of amoxicillin for two weeks was substituted for one single injection of intramuscular depot penicillin (benzathine penicillin G). Additionally, patients were given ornidazole 500 mg tid for 14 days and 120 mg colloidal bismuth sub-citrate qid for 28 days. The patients were investigated for H. pylori colonization using a rapid urease test (CLO), histology (H&E-, Giemsa stain), culture (including determination of the minimal inhibitory concentrations for metronidazole, penicillin G and amoxicillin) and H. pylori serology (Cobas Core Anti-H. pylori EIA, F. Hoffmann-La Roche). Control endoscopies using the same methods were performed 1 and 6 months after eradication therapy. The eradication rate was 50% and the ulcer healing rate 90% 1 month after therapy. Ulcers recurred in 2/3 of patients with persistent infection vs 0/5 of HP-eradicated patients after 6 months. Both successfully HP-eradicated patients and patients with treatment failure exhibited comparable decreases in mean serum IgG anti-HP concentration within 2 months. Discrimination between the two groups and hence identification of the eradication success by serology was not possible within a time period of 2 months. After 6 months, serum IgG anti-HP concentrations in non-HP-eradicated patients returned to pre-therapy values, in HP-eradicated patients the concentrations further decreased. The above-described modified triple therapy against HP cannot be recommended as a standard therapy, mainly because of the insufficient eradication effect.(ABSTRACT TRUNCATED AT 250 WORDS)

[Alpha-interferon therapy in Crohn's disease: initial clinical results]. / Alpha-Interferon-Therapie bei M. Crohn: erste klinische Erfahrungen.

4 therapies in 3 patients (1 female, 2 male) suffering from steroid dependent Crohn's disease are described. Interferon alpha-2b was administered for 24 weeks (3 million I.U. per day for 4 weeks, and 3 x 3 million U.I. per week for 20 weeks). Prednisolone dosage at start of therapy depended on initial inflammatory activity (CDAI). The daily dose was reduced stepwise and omitted after 12 weeks. In two courses patients did not respond and therapy had to be halted after 12 and 14 weeks' duration because of increasing disease activity. During the other two treatments a decrease in disease activity of 118 and 70 CDAI units (in both cases after 8 weeks) could be achieved. In particular, the course in one patient with abundant intestinal and extraintestinal inflammatory activity was quite impressive: extraintestinal activity disappeared completely within 10 days, CDAI ameliorated substantially for 30 weeks and the patient could be treated without steroids for a total period of 18 weeks. As a preliminary conclusion from the cases described up to now, it can be speculated that females probably respond more favorably to a combined therapy with interferon alpha and corticosteroids. Moreover, we suggest that the potential of interferon in Crohn's disease might be to overcome a steroid refractory disease state rather than to allow omission of steroid medication which could not be further reduced without exacerbation. Clearly, present experience of interferon therapy in Crohn's disease is still too scarce and more work needs to be done to define the role of interferon in IBD.

[Spontaneous rupture of the left hepatic duct]. / Spontane Ruptur des Ductus hepaticus sinister.

A previously well 24-year-old man complained of persistent epigastric pain after a session of intensive muscle building exercise especially of the abdominal muscles. The abdomen was diffusely tender without guarding. There was an increased concentration of bilirubin (64.7 mumol/l), GOT (117 U/l), GPT (529 U/l) and alkaline phosphatase (150 U/l). Ultrasound examination showed a widening of the choledochal duct to 11 mm without signs of gallstones. Endoscopic retrograde cholangiography additionally revealed contrast-medium extravasation from the left hepatic duct. Computed tomography, performed immediately afterwards, confirmed the extravasation, while liver and pancreas were unremarkable. Laparoscopy revealed a 5 mm tear in the left hepatic duct, close to the hepatic duct bifurcation with bile effusion into the peritoneal cavity. The latter was rinsed endoscopically with Ringer's solution and drains were placed in the omental bursa and subhepatically in the region of the bile leak. To relax the sphincter Oddi glycerol trinitrate was administered postoperatively, for the first five days 72 mg/24 h intravenously, then for nine days twice daily 20 mg by month. No more bile drained as early as the second postoperative day and the patient was free of symptoms 2 weeks later.

Pancreatic and hepatic abscesses: a late complication in 10 patients with chronic pancreatitis.

In this prospective long-term study of chronic pancreatitis (n = 336) over the last 3 decades, 10 patients with advanced calcific pancreatitis developed a sepsis associated with intra-abdominal abscesses (6 pancreatic, 4 hepatic). None of the known precipitating factors were present (e.g., no pancreatic necrosis or recent surgical/endoscopic interventions, no evidence of cholangitis). Nine of 10 patients had alcoholic chronic pancreatitis. Interestingly a pancreatojejunostomy in 9 of 10 patients had been performed up to 12 years previously. Cultures from abscess aspirates and/or blood were polymicrobial, mainly a mixed enteric flora in 8 patients. All patients recovered after an appropriate antibiotic therapy with or without drainage procedures. The pathogenesis of "spontaneous" abscess formation in advanced chronic pancreatitis and its relationship to pancreatojejunostomy remain to be established.

[Colonoscopic endosonography in the diagnosis and follow-up care of colorectal tumors]. / Koloskopische Endosonographie in der Diagnostik und Nachsorge kolorektaler Tumoren.

We studied the usefulness and accuracy of a flexible endoscopic ultrasound system (EUS) in preoperative staging of tumor invasion and involvement of lymph nodes of rectal tumors. Comparison of preoperative EUS findings with histopathologic TNM classification (UICC 1987) was possible in 12 patients. The depth of tumor invasion was correctly staged in 9/12 patients (75%), and lymph node staging was correctly predicted in 9/12 patients (75%). Our results indicate that flexible coloscopic ultrasonography is as accurate as rigid systems for staging of colorectal cancer. It will become a sensitive method for early diagnosis of local recurrence. The flexible endoscopes are well tolerated by patients and more proximal lesions which cannot be reached with the rigid instruments can also be examined.

[Endosonography: progress in the diagnosis of endocrine pancreatic tumors]. / Endosonographie: ein Fortschritt in der Diagnostik endokriner Pankreastumoren.

Diagnostic procedures for secreting endocrine pancreatic tumors comprise biochemical tests, CT scans, conventional abdominal sonography, angiography and occasionally MR imaging and isotope scans. Due to their small size, insulinomas and gastrinomas, the most common of these tumors, elude these diagnostic procedures. Preoperative sonography and CT scans were negative in over 60%, angiograms in 35% of the patients. The example of a patient with insulinoma demonstrates that in the future endosonography will offer itself as an accurate method with little risk.