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Eighty-two patients with Hodgkin's disease (H.D.) and 40 patients with Multiple Myeloma (M.M.) were HL-A typed. The results were compared with those of 255 healthy individuals of the same geographical area. In both diseases W18 (4cr) - belonging to the 4c-complex - was significantly increased.

The sensitivity and specificity of ultrasound-directed fine-needle biopsy in the differentiation of malignancy or otherwise of structures in the abdomen or retroperitoneal space which look suspicious on ultrasound was evaluated from results in 558 patients (306 men, 252 women). Data from two different centres were used to characterize further the influence of different techniques of puncture, cytopathologists and groups of patients on the validity of the examination. Sensitivity (in the two centres) was 88 and 80%, respectively, specificity 100 and 99%. The validity of the examination was the same at both centres. In both centres the sensitivity was worst for pancreatic tissue, at only 72 and 61% respectively, compared with other organs (e.g. liver, lymph nodes, kidney) (P less than 0.05). Fine-needle biopsy of abdominal and retroperitoneal organs will thus be subject to a not insignificant number of false-negative results of cytological examination.

Bei drei Patienten (einem 40jahrigen und einem 31jahrigen Mann sowie einer 30jahrigen Frau) trat im Rahmen eines Colitis-ulcerosa-Schubes ein Protein-C-Mangel auf: Die Serum-Protein-C-Aktivitat lag zwischen 32 und 48 %. Wahrend der Protein-C-Mangel bei den beiden Mannern erst nach Auftreten schwerer thromboembolischer Komplikationen (Sinus-cavernosus-Thrombose, Lungenembolien) unter Heparintherapie festgestellt wurde, wurde die Protein-C-Aktivitat bei der Frau in Kenntnis der beiden ersten Falle unmittelbar nach der Klinikaufnahme bestimmt, noch vor einer Heparintherapie. In allen Fallen erfolgten eine Colitis-ulcerosa-Therapie mit Sulfasalazin (3 g/d) und Fluocortolon (60 mg/d) sowie eine Vollheparinisierung (22 500-36 000 I.E./d). Mit der Remission der Colitis ulcerosa (in einem Fall erst nach subtotaler Kolektomie) normalisierte sich die Protein-C-Aktivitat wieder. Diese Beobachtungen weisen auf einen erworbenen Protein-C-Mangel hin, der durch konsequente Therapie der Grundkrankheit zu beseitigen ist. Three patients with an a acute exacerbation of ulcerative colitis (a 40-year-old and a 31-year-old man and a 30-year-old woman) developed a protein C deficiency (serum protein C activity between 32 and 48 %). In the two men the protein C deficiency was diagnosed only after the onset of severe thromboembolic complications (cavernous sinus thrombosis; pulmonary embolism) during heparin treatment. But in the woman protein C activity was measured immediately after hospital admission (in the knowledge of the first two cases) even before heparin administration was started. All three patients received treatment with sulphasalazine (3 g daily) and fluocortolone (60 mg daily), as well as full heparinization (22,500-36,000 IU daily). Protein C activity returned to normal on remission of the ulcerative colitis (in one case only after subtotal colectomy). - These case reports show that acquired protein C deficiency can be reversed by rigorous treatment of the underlying disease.

Intensive induction therapy in acute myeloid leukemia (AML) as in some other systemic malignancies is a strategy fundamentally different from post-remission strategies. Approaches such as consolidation treatment, prolonged maintenance, and autologous or allogeneic transplantation in first remission are directed against the minimal residual disease in which a malignant cell population has survived induction treatment and shows resistance due to special genetic or kinetic features. In contrast, induction therapy deals with naive tumor cells possibly different from their counterparts in remission in terms of their kinetic status and sensitivity. Therefore, in AML the introduction of intensification strategies into the induction phase of treatment has been suggested as a new step in addition to intensification in the postremission phase. As expected from the dose effects observed in post-remission treatment with high-dose cytarabine (AraC) or longer treatment, similar dose effects have been found in induction treatment both from the incorporation of high-dose AraC and from the double-induction strategy used in patients up to 60 years of age. As a particular effect, patients with poor-risk AML according to an unfavorable karyotype, high LDH in serum, or a delayed response show longer survival following double induction containing high-dose AraC as compared to standard-dose AraC. A corresponding dose effect in the induction treatment of patients aged 60 years and older has been found with daunorubicin 60 vs 30 mg/m2 as part of the thioguanine/ AraC/daunorubicin (TAD) regimen with the higher dosage significantly increasing the response rate and survival in these older patients who represent a poor-risk group as a whole. Thus we have been able to demonstrate both in younger and older patients that a poor prognosis can be improved by a more intensive induction therapy. High-dose AraC in induction, however, exhibits cumulative toxicity in that repeated courses containing high-dose AraC in the post-remission period lead to long-lasting aplasias of about 6 weeks. Thus after intensive induction treatment, high-dose chemotherapy in remission may be practicable using stem-cell rescue and may contribute to a further improvement in the outcome in poor-risk as well as average-risk patients with AML. These approaches are currently under investigation by the German AML Cooperative Group (AMLCG). "The more intensive the better" is certainly not the way to go in the management of AML and other systemic malignancies but some increase in intensity may be possible and better.

In a prospective randomized multicentre trial 139 patients with metastatic colorectal carcinoma (70 men, 69 women; age 35-81 years) were given palliative treatment with fluorouracil (400 mg/m2 daily for 5 days) alone or combined with folic acid (100 mg/m2 before each dose of fluorouracil). Both groups were comparable in respect of age, sex, Karnofsky index and number of localisations of metastases. The criterion for starting the treatment was progression of the malignancy or clinical symptoms caused by the tumour. Resulting remission rates (fluorouracil monotherapy vs combination with folic acid) were: complete or partial remission, 9 vs 16%; arrest of tumour growth, 20 vs 60%; progression 71 vs 24%. Peripheral side effects, such as stomatitis and diarrhoea, were similarly frequent with the two treatment regimens and reasonably tolerable. Median survival time for the fluorouracil monotherapy was 7.24 months from onset of treatment, and 9.1 months from the time that any metastases were diagnosed. The combination treatment with folic acid achieved a significantly longer median survival time (P less than 0.0001), 14.98 months from treatment onset and 16.3 months from metastasis diagnosis. The higher rate of response and the significantly prolonged survival time signify an improvement of the therapeutic profile of fluorouracil by addition of folic acid in the palliative therapy of colorectal carcinomas.

We report here on a 44-year-old previously healthy patient with a two-year history of intermittent upper abdominal pain. In the outpatient gastroduodenoscopy and X- ray examinations of the small intestine an intraluminal duodenal diverticulum was suspected. Clinical examination and laboratory tests did not show any abnormal findings. In order to exclude other causes for the patient's complaints coloscopy, ERP and MRCP were performed. The latter was done because the bile duct could not be intubated in the ERCP due to the altered anatomy. By use of endoscopic ultrasound a mucosal duplication was demonstrated and thus the diagnosis confirmed. Subsequently, the diverticulum sac was sliced by argon plasma coagulation. The postinterventional course was without complications and the patient was without symptoms afterwards. The intraluminal duodenal diverticulum is a rare differential diagnosis of pain in the upper abdomen. The diverticulum should be endoscopically removed if other causes for abdominal pain have been ruled out and possibly associated malformations have been excluded.

We report a case of a 26-year-old female patient who was referred to our hospital with a painless jaundice. By means of an ERCP we found a nearly complete occlusion of the common bile duct caused by a tumor. After stenting and normalization of the cholestasis parameters, additional investigations such as endosonography, cholangioscopy and MR angiography no longer showed any manifestation of the tumor. The histological and cytological specimens did not confirm a malignant process. As there was apparently only a solitary tumor a resection according to Whipple was performed. The histological examination showed a granular cell tumor. This case report demonstrates that a posthepatic icterus may rarely be caused by a granular cell tumor. Furthermore, it clearly shows the difficulty to correctly diagnose a tumor in the extrahepatic common bile duct as one may often have to rely solely on imaging procedures.

The outcome in patients with AML appears influenced by some therapeutic variables such as different intensity chemotherapy, growth factor priming, autologous or allogeneic transplantation. Even more than by treatment variables the outcome is determined by genetic and functional features related to the individual disease biology. Open questions are how far these prognostic factors apply to the different treatment options and whether the prognosis in specific subgroups can be improved by specific treatment. We here present a new study strategy using upfront randomization for major treatment alternatives, stratified for de novo versus secondary AML versus MDS, and for their biologic subgroups thus allowing unbiased analyses of subgroup-specific effects by specific treatments.

Maintenance treatment for patients with acute myeloid leukemia (AML) in remission has recently been controversially discussed and even abandoned by several groups. An analysis of 14 recently published multicenter trials, however, revealed the highest probabilities of relapse-free survival (RFS), in the range of 35% to 42% at 4 to 5 years, only in patients assigned to maintenance treatment as far as adult age and intent-to-treat conditions were considered. After having demonstrated a superior RFS rate from 3 years of maintenance after standard-dose consolidation compared with that from consolidation alone (P = .00004), the German AMLCG requestioned the effect of maintenance randomly compared with sequential high-dose cytosine arabinoside (Ara-C) and mitoxantrone in patients who received intensified induction treatment. The results show an advantage for maintenance treatment (RFS rate of 32%) versus the sequential Ara-C and mitoxantrone treatment (RFS rate of 25%) (P = .021). We conclude that maintenance treatment continues to substantially contribute to the management of adult patients with AML, even as part of recent strategies using intensified induction treatment, and thus appears necessary in these settings.

We report on 4 patients who were referred to the clinic with suspected acute hepatitis and to investigate high transaminase values. After exclusion of specific hepatitis, unspecific virus hepatitis, autoimmune hepatitis, a metabolic disorder damaging the liver and extrahepatic cholestasis, a toxic liver damage remained as the probable cause and was histologically verified. Since other drugs and alcoholics could be eliminated as possible causes of the damage, the toxicity had to be attributed to statin ingestion.After discontinuation of the medication with continuation of all other therapeutic agents of the general practitioners, the transaminase values normalized within a few weeks. Renewed administration of statin was not prescribed for ethical reasons.Therefore, when prescribing a HMG-CoA-reductase inhibitor, the possibility of liver damage should be mentioned and regular checks of the transaminase values should be performed.

Endoscope-guided fine-needle biopsy of mediastinal space-occupying lesions is a recently introduced method of low invasiveness. This is a report of the authors' experience.Between Nov. 1996 and April 1999 endoscope-guided mediastinal biopsies (Pentax FG 32 UA) were performed in 31 patients (eight women, 23 men; aged 27-80 years). The space-occupying lesion had to be less than 1 cm from the oesophagus and not more easily approachable in other ways.The method was successful in 23 of the 31 patients (74%). In ten of the 31 patients (32%) a malignant lesion was histologically proven. In six patients (19%) sarcoidosis was revealed. Of the eight patients with inadequate biopsy material a malignancy was ultimately diagnosed in three, sarcoidosis in one (in three by mediastinoscopy, in one by laparoscopy). Thus the sensitivity of diagnosing a malignancy was 77%, with a specificity of 100%. Follow-up examinations in the remaining four patients excluded a malignancy.Endoscope-guided fine-needle biopsy of mediastinal space-occupying lesions is a technically simple method causing little stress to the patient that can frequently elucidate the lesion's benignity or malignancy. Invasive procedures, such as mediastinoscopy, may thus be avoided in some patients.

Sarcoidosis is a chronic multisystem disorder of unknown cause characterized by the presence of noncaseating epitheloid granulomas and derangement of the normal skin architecture. Though an array of organs may be affected by the disease the most common site of affection is the lung. An extrathoratic manifestation is rare. We describe a 66-year-old patient who was admitted to our hospital because of weight loss and hepatomegaly. A thorough examination revealed the diagnosis of a granulomatous hepatitis characterized by a markedly elevated alkaline phosphatase concentration of 1,490 U/I. A drug-induced hepatitis could be excluded and no evidence was found for the existence of a bacterial or viral infection or an autoimmune disorder. An ERCP revealed a normal common bile duct and normally branching small intrahepatic ducts. The patient was discharged with the diagnosis of a biliary cirrhosis. Half a year later the patient was readmitted to the hospital because of severe intestinal bleeding due to pancytopenia. A bone marrow biopsy showed infiltration of the marrow by granulomas. A histiocytosis X could be ruled out. The diagnosis of an extrathoracic sarcoidosis was assumed and a therapy with prednisone was started. Within six weeks the blood count normalized. After 18 months the serum alkaline phospatase concentration also normalized and no granulomas were found in the bone marrow. The case demonstrates that pancytopenia in sarcoidosis is not due to bone marrow failure.

We evaluated the clonal relationship between a case of nodular sclerosis Hodgkin's disease (NSHD) and a small noncleaved cell (SNC) lymphoma that subsequently developed. Single Hodgkin and Reed-Sternberg (H-RS) cells were isolated from immunostained sections of the NSHD by micromanipulation, and the immunoglobulin heavy chain gene (IgH) complementarity determining region (CDR) III of the cells was amplified by the polymerase chain reaction (PCR). A clonal population of H-RS cells was found in the NSHD tumor. The nucleotide sequence of the clonal H-RS cells was compared with the clonal IgH CDRIII sequence from the SNC lymphoma. The two sequences were found to be unrelated. In addition, clone-specific primers and probes were designed from the two clonal IgH CDRIII sequences and used to investigate the presence of the respective clonal population in the NSHD tumor. The latter studies confirmed the presence of a major clonal H-RS cell population, as detected by the single cell assay, but cells corresponding to the SNC clone were not demonstrable by this highly sensitive technique. These findings suggest that the SNC arising in this case represents the development of the second neoplasm clonally unrelated to the preceding NSHD. They also support the recent findings that the H-RS cells in classical HD consist of a clonal population of B cells.

DNA ploidy and cell cycle phases were evaluated by flow cytometry in colonic biopsy specimens from 107 patients with ulcerative colitis in order to analyse the prevalence of DNA aneuploidy as an indicator of numerical chromosomal aberrations and the cell proliferation in all forms of ulcerative colitis. Whereas G2/M-phase fractions in ulcerative colitis and in controls were comparable (2.7 +/- 1.1% vs. 2.8 +/- 1.1%), S-phase fractions in ulcerative colitis exceeded those of controls (7.5 +/- 3.2% vs. 6.5 +/- 2.3%; p0.01). In 28 control patients, only diploid DNA histograms existed. Single or multiple aneuploid stem lines were detected in 10 patients with ulcerative colitis (9.3%). Aneuploidy was nearly exclusively associated with pancolitis. Dysplasia was present in 13 patients (indefinite: 8; low-grade: 5), of whom 5 patients also showed DNA aneuploidy. 5 patients with non-dysplastic mucosa exhibited DNA aneuploidy. Because dysplasia and DNA aneuploidy can be discordant and might therefore identify different subgroups at risk, flow cytometry might play a role as a valuable complement to histological examination in surveillance programs of ulcerative colitis.

In a prospective randomized multicentre trial 139 patients with metastatic colorectal carcinoma (70 men, 69 women; age 35-81 years) were given palliative treatment with fluorouracil (400 mg/m2 daily for 5 days) alone or combined with folic acid (100 mg/m2 before each dose of fluorouracil). Both groups were comparable in respect of age, sex, Karnofsky index and number of localisations of metastases. The criterion for starting the treatment was progression of the malignancy or clinical symptoms caused by the tumour. Resulting remission rates (fluorouracil monotherapy vs combination with folic acid) were: complete or partial remission, 9 vs 16%; arrest of tumour growth, 20 vs 60%; progression 71 vs 24%. Peripheral side effects, such as stomatitis and diarrhoea, were similarly frequent with the two treatment regimens and reasonably tolerable. Median survival time for the fluorouracil monotherapy was 7.24 months from onset of treatment, and 9.1 months from the time that any metastases were diagnosed. The combination treatment with folic acid achieved a significantly longer median survival time (P less than 0.0001), 14.98 months from treatment onset and 16.3 months from metastasis diagnosis. The higher rate of response and the significantly prolonged survival time signify an improvement of the therapeutic profile of fluorouracil by addition of folic acid in the palliative therapy of colorectal carcinomas.

Three patients with an acute exacerbation of ulcerative colitis (a 40-year-old and a 31-year-old man and a 30-year-old woman) developed a protein C deficiency (serum protein C activity between 32 and 48%). In the two men the protein C deficiency was diagnosed only after the onset of severe thromboembolic complications (cavernous sinus thrombosis; pulmonary embolism) during heparin treatment. But in the woman protein C activity was measured immediately after hospital admission (in the knowledge of the first two cases) even before heparin administration was started. All three patients received treatment with sulphasalazine (3 g daily) and fluocortolone (60 mg daily), as well as full heparinization (22,500-36,000 IU daily). Protein C activity returned to normal on remission of the ulcerative colitis (in one case only after subtotal colectomy). These case reports show that acquired protein C deficiency can be reversed by rigorous treatment of the underlying disease.

Infection is a major cause of morbidity and mortality in patients undergoing hemodialysis for end stage renal disease. Low plasma zinc levels have been associated with immunodepression in these patients. In a randomized, placebo controlled double-blind cross over study, plasma zinc levels, delayed hypersensivity to 7 Antigens (Merieux-Multitest), absolute lymphocyte counts, T- and B-lymphocytes, suppressor-T and helper T-cells and natural killer cells were studied in 25 hemodialysis patients before, during and after intravenous zinc supplementation for 8 weeks. The hemodialysis patients had significantly lower predialysis plasma zinc concentrations compared to 76 healthy controls (74 +/- 12 vs. 126 +/- 28 mcg/dl, p less than 0.001). The plasma zinc concentrations increased to the normal range during the treatment period. Lymphocyte subtype analysis showed a significant decrease of suppressor-T cells and an increase of the helper-T/suppressor-T ratio (2.09 +/- 0.26 vs. 3.18 +/- 0.48, p less than 0.05) after zinc supplementation. Delayed hypersensivity to intradermal antigens increased significantly only after zinc treatment (2.0 +/- 0.7 vs. 5.8 +/- 1.7, p less than 0.05), not after placebo. The changes were reversible after finishing the zinc treatment. It is concluded, that plasma zinc levels are reduced in hemodialysis patients and that the substitution of zinc restores some of the depressed immune functions in these patients.

Zinc is an essential component of many metalloenzymes for DNA and proteinsynthesis including RNA and DNA polymerases. It has been shown by several investigators that zinc is accumulated in breast cancer tissues. To investigate a possible relation between plasma zinc levels and tumor load, plasma zinc levels were evaluated in 76 patients with non metastatic breast cancer (no evidence for disease after mastectomy) and in 66 patients with metastatic breast cancer. Zinc concentrations were measured in plasma using an atomic absorption spectrophotometer (normal range 80-150 mcg/dl). In patients with metastatic disease plasma zinc concentrations were in the lower region of the normal range or depressed (arithmetic mean: 84.9 SD 21.6 mcg/dl), whereas patients with non metastatic breast cancer had normal zinc levels (arithmetic mean: 126.0 SD 27.7 mcg/dl). The difference between the two groups was highly significant (p = 0.001, t = -9.742, 140 degrees of freedom). It is concluded, that plasma zinc in breast cancer patients is depressed according to the stage of the disease. Based on experimental data a substitution of zinc cannot be recommended.

The sensitivity and specificity of ultrasound-directed fine-needle biopsy in the differentiation of malignancy or otherwise of structures in the abdomen or retroperitoneal space which look suspicious on ultrasound was evaluated from results in 558 patients (306 men, 252 women). Data from two different centres were used to characterize further the influence of different techniques of puncture, cytopathologists and groups of patients on the validity of the examination. Sensitivity (in the two centres) was 88 and 80%, respectively, specificity 100 and 99%. The validity of the examination was the same at both centres. In both centres the sensitivity was worst for pancreatic tissue, at only 72 and 61% respectively, compared with other organs (e.g. liver, lymph nodes, kidney) (P less than 0.05). Fine-needle biopsy of abdominal and retroperitoneal organs will thus be subject to a not insignificant number of false-negative results of cytological examination.

The incidence of hypoglycemia was determined in 138 type-2 diabetics treated with insulin (40%) or sulfonylureas (60%). Within one year, ten patients (7%) experienced one severe hypoglycemic episode characterized by a loss of consciousness and the necessity of parenteral glucose administration. Insulin treatment and advanced age increased the risk of hypoglycemia. The knowledge about hypoglycemia was poor. Only 45% of the patients could give a correct definition, 18% knew more than two symptoms, and 15% knew at least one cause of hypoglycemia. 66% would treat hypoglycemia with oral carbohydrates. The risk of hypoglycemia should be considered in the planning of adopted teaching and treatment programs for patients with type-2 diabetes.

Durch die sonographisch geleitete Punktionszytologie (FNP) wird die zytologische Untersuchung abdominell und retroperitoneal gelegener Strukturen ermoglicht. In der vorliegenden Studie wurde untersucht, welche Validitat diese Methode hinsichtlich der Differenzierung zwischen mahgner und benigner Lasion aufweist. Insbesondere sollte geklart werden, ob bei den verschiedenen Abdominalorganen Unterschiede in der Treffsicherheit bestehen und ob die Treffsicherheit zwischen verschiedenen Zentren varuert. Hier interessierte uns einerseits, wie stark der diagnostische Wert der FNP von der unterschiedhchen Erfahrung verschiedener Untersucher beeinflust wird, und ob sich andererseits auch allgemein gultige, prinzipielle Einflusfaktoren herausarbeiten lassen.

Es wird uber kritische Punkte in der Methodik der CEA-Bestimmung nach Hansen u.a. (CEA-RIA-Test der Firma Hoffmann-La Roche) berichtet. Bei 82 Patienten mit colorectalem Carcinom konnte die CEA-Bestimmung durchgefuhrt werden. Postoperativ wurden bei 43 Patienten 4 Tage, 8 Tage, 14 Tage, 3 Monate und 6 Monate, vereinzelt auch spater, die CEA-Werte beobachtet. Von 61 praoperativ bestimmten Patienten lagen 52,5% uber der vorgeschlagenen Normgrenze von 2,5 ng/ml. Bei der statistischen Auswertung mit der Multivarianzanalyse ergab sich eine Wechselwirkung der verschiedenen Stadien auf die CEA-Werte. Postoperativ fallen die CEA-Werte unterschiedlich rasch ab. Ein Wiederanstieg des CEA-Wertes zeigt bereits weit vor der klinischen Manifestierung das Rezidiv an. In einem Fall wurde pra- und postoperativ trotz Lebermetastasen kein erhohter CEA-Wert gemessen. Erst 11 Monate postoperativ, nach Generalisierung der Erkrankung, konnte ein erhohter CEA-Wert nachgewiesen werden. Es sollte deshalb auch bei normalen CEA-Werten die Verlaufskontrolle fortgesetzt werden.

Two patients with extramedullary manifestation of the blastic phase of chronic myelocytic leukemia (CML) are reported. 100% of the metaphases derived from extranedullary sites were aneuploid. Despite the absence of blastic changes in the bone marrow and the peripheral blood, a significant proportion of the metaphases derived from these tissues also showed aneuploidy. It is suggested that maturation and differentiation of aneuploid myeloblasts are influenced by their environment.

Die Seren von insgesamt 282 Patienten mit verschiedenen Formen der Hepatitis und Cirrhose wurden auf das Vorhandensein lymphocytarer Antikorper untersucht. Bei diesen Antikorpern handelt es sich um 19S-IgM-Immunglobuline, die in vitro optimal bei einer Temperatur von 15°C unter Komplementverbrauch reagieren und keine HLA-Spezifitat aufweisen. Sie waren in Prozentsatzen zwischen 14% und 48% bei Patienten mit Hepatopathien nachweisbar, wobei die hochste Frequenz bei chronisch-aggressiver Hepatitis (CAH) und die niedrigste bei Patienten mit chronisch-persistierender Hepatitis (CPH) beobachtet wurden. Bei Patienten mit akuter Hepatitis (blander und rezidivierender Verlauf) lag die Haufigkeit des Nachweises der Kaltelymphocytotoxine (Cold reactingComplement dependant lympho-Cytotoxins=CoCoCy) zwischen denjenigen der CAH- und CPH-Patienten. Eine Korrelation zum Hepatitis-B-Antigen bestand nicht. Diese Antikorper waren nicht nur bei Leberpatienten, sondern auch in der Kontrollgruppe der HB-Ag-positiven und HBAg-negativen Blutspender in 20% bzw. 6% nachweisbar. Die Serumkonzentration der CoCoCy ist gering. Der Nachweis dieser Antikorper ist weniger von diagnostischem als von pathogenetischem Interesse. Moglicherweise sind die CoCoCy ein „Brutto-Parameter“ fur die Immunreaktivitat. Sie besitzen wahrscheinlich T-Zell-Spezifitat und sind unabhangig von dem spezifischen Antigenstimulus der Immunreaktion.

The spontaneous rossette-formation of lymphocytes and the rate of the DNA-synthesis was determined in 33 uremic patients of the haemodialysis unit. 1. Spontaneous rosette-formation of uremic lymphocytes (39,5%,n=16) did not differ from normal lymphocytes (39,3%,n=39). 2. The absolute lymphocyte count was slightly but not significantly reduced in uremic patients compared to normal controls and the slight increase after dialysis was not significant. 3. The PHA-induced DNA-synthesis of lymphocytes of 23 uremic patients was significantly reduced compared to normal controls. 4. The reduced PHA-induced DNA-synthesis of lymphocytes of uremic patients was not different in patients dialysed two times (22 hours) per week and patients dialysed three times (30 hours) per week. 5. No correlation of the reduction of PHA-induced DNA-synthesis to the underlying renal-diseases could be found.

Bei 12 Patienten mit terminaler Niereninsuffizienz, die im chronischen Hamodialyseprogramm stehen, wurde die Stimulierbarkeit der Lymphocyten durch PHA unmittelbar vor und bei 11 Patienten nach Abschlus einer 12stundigen Dialyse bestimmt. 1 Vor der Dialyse wurde eine signifikante Reduktion der Lymphocytenstimulierbarkeit chronisch niereninsuffizienter Patienten (Median=12000 IpM,n=12) gegenuber Normalpersonen (Median=37000 IpM,n=24) gemessen. 2 Nach der Dialyse fand sich eine signifikante Steigerung der PHA-Stimulierbarkeit bei den Patienten-Lymphocyten (Median=25000 IpM,n=11). 3 Die Vitalitatsmessung der Lymphocyten ergab deutlich erniedrigte Uberlebensraten bei 8 Patienten mit chronischer Niereninsuffizienz (t/2=4 Tage) gegenuber 9 Kontrollpersonen (t/2=9 Tage). 4 Auch bei Verlaufskontrollen und Untersuchungen der DNS-Synthesekinetik uramischer Lymphocyten vor und nach Dialyse bestatigte sich der steigernde Dialyseeffekt.

Mit dem Ziel, neue Voraussetzungen fur experimentelle, histologische und biologische Untersuchungen der menschlichen Prostata zu schaffen, haben wir humanes Prostataadenomgewebe in die Oberschenkelmuskulatur neonataler Ratten verpflanzt. Die notwendige Immunsuppression wurde durch subcutane Injektion von Antilymphocytenserum erzielt. 3 Wochen nach der Heterotransplantation entsprach das histologische Bild eines Teils des implantierten Prostataadenomgewebes weitgehend dem Originalgewebe. Ebenso verhielten sich histochemischer Reaktionsausfall und Verteilungsmuster der sauren Phosphatase, der unspezifischen Esterase und der Succinodehydrogenase. Daneben wurden metaplastische Drusenstrukturen angetroffen, die durch einen Aktivitatsabfall der untersuchten Enzyme gekennzeichnet waren.

1. Der Ca-Gehalt und die 45Ca-Menge im isolierten Rattenzwerchfell wurden gleichzeitig bestimmt. Ca wird mittels einer Fluorescenz-spektro-photometrischen Methode und 45Ca durch Flussigkeits-Scintillations-Zahlung gemessen.

Individuelle normale IgG wurden isoelektrisch in eine Vielzahl von Komponenten getrennt, deren IP zwischen pH 5,5 und 9,5 lagen. Im Gegensatz dazu focussierten individuelle Myelom IgG einheitlich. Die isoelektrischen Punkte dieser Paraproteine unterschieden sich untereinander stark, verteilten sich alle zusammen jedoch ebenfalls uber den pH-Bereich 5–9. Dieser Befund entspricht der Auffassung, das diese Paraproteine normale Immunglobuline reprasentieren.

Durch isoelektrische Trennung gelang es,l-Asparaginase von E. coli in zwei enzymaktive Komponenten F 1 und F 2 mit den isoelektrischen Punkten pH 5,26 und 5,07 zu fraktionieren. Eine dritte nicht enzymaktive Eiweiskomponente mit einem isoelektrischen Punkt von 4,89 ist als E. coli-eigenes unspezifisches Protein anzusehen.

Am Beispiel des Albumins wird die isoelektrische Trennung von Bluteiweiskorpern auf Tragerampholyten demonstriert. Mit der Methode lies sich eine Auftrennung des Albumins in mehrere Komponenten mit unterschiedlichen isoelektrischen Punkten erreichen. Die verschiedenen Fraktionen verteilen sich hinsichtlich ihres isoelektrischen Punktes uber den pH-Bereich pH 4,7–5,6. Die Ursachen dieser Heterogenitat werden im Zusammenhang mit der entsprechenden Literatur diskutiert.

Das Verfahren der isoelektrischen Trennung hat der analytischen Proteinchemie neue Moglichkeiten eroffnet. Mittels Elektrofocussierung ist es moglich, auf einfache Art den isoelektrischen Punkt von Proteinen genau zu bestimmen und Proteine mit unterschiedlichem isoelektrischem Punkt zu trennen und anschliesend zu praparieren. Nach Erlauterung des Prinzips und der Entwicklung des Verfahrens werden die Unterschiede und Vorteile der isoelektrischen Analyse gegenuber den elektrophoretischen Trennungen besprochen. Es wird ein Uberblick uber bisherige Ergebnisse gegeben und Fehlermoglichkeiten bei der Durchfuhrung der Methodik diskutiert.

Erfolgreich lies sich die Verpflanzung von menschlichem Prostatagewebe auf neonatale Ratten, die mit Antilymphocytenserum behandelt wurden, durchfuhren. Die Transplantationstechnik einschlieslich der Herstellung des Antilymphocytenserums und der histologischen Aufarbeitung der Transplantate wird beschrieben.

1. Isolierte, normale und chronisch denervierte Rattenzwerchfelle werden fur 15 min in einer 45Ca-haltigen Tyrode-Losung inkubiert und anschliesend die 45Ca-Abgabe aus den Muskeln bestimmt. Gleichzeitig wird der Ca-Gehalt gemessen. 2. Die chronisch denervierten Muskeln besitzen denselben Ca-Gehalt und geben 45Ca mit derselben Geschwindigkeit ab wie die normalen Muskeln. Die Abgabe-Kurven lassen sich in zwei Phasen zerlegen, eine schnelle Komponente mit der Halbwertzeit von ca. 4 min und einem Anteil von 78% und einer langsamen Komponente mit der Halbwertzeit um 70 min. 3. Die schnelle Komponente besteht aus dem extracellularen 45Ca und einem cellularen 45Ca-Anteil. Nach Depolarisation des normalen Muskels mit Kalium-Ionen verschwindet die schnelle cellulare 45Ca-Fraktion, die langsame Komponente nimmt entsprechend zu. 4. Noch ausgepragter ist die Verlangsamung der 45Ca-Abgabe am chronisch denervierten Rattenzwerchfell in Anwesenheit von Carbachol, wahrend Kalium-Ionen denselben Effekt hervorrufen wie am normalen Muskel. 5. Es wird geschlossen, das die Zellmembran eine frei bewegliche Ca-Fraktion besitzt.

Zum Studium der unter ALS-Behandlung beschriebenen Nephritis wurden Ratten mit Kaninchenantirattenlymphocytenserum (ALS), Antilymphocytenglobulin (ALG) und als Kontrollen normalem Kaninchenserum (NS) und normalem Kaninchenglobulin (NIG) behandelt. Es zeigten sich ausschlieslich Veranderungen einer Serumnephritis, die unter ALS und ALG haufiger und in starkerer Auspragung auftraten als unter NS und NIG. Zeichen einer nephrotoxischen Nephritis waren unter der verwendeten, aus gereinigten Lymphknotenlymphocyten hergestellten ALS-Praparation nicht nachzuweisen.

A mobile pedunculated polypoid tumor was endoscopically removed from the afferent jejunal loop after gastrojejunostomy of a 54-year-old patient with anamnestic evidence of intestinal bleeding. Histologically epithelial carcinoid-like as well as mesenchymal paraganglioma- and ganglioneuroma-like patterns are mixed in varying portions, characteristic for gangliocytic paraganglioma. Immunohistochemically, serotonin, neuron-specific enolase, cytokeratin, vimentin S-100 protein and neurofilament were demonstrable. Gangliocytic paragangliomas are almost exclusively observed in the second portion of the duodenum, especially around the papilla Vateri and only two have previously been reported in the jejunum. The histogenesis of the tumors is unclear, but they may probably be either hamartomas, hyperplastic or neoplastic proliferations of so called endodermal-neuroectodermal complexes. Although gangliocytic paragangliomas contain a carcinoid-like component, they behave in a benign fashion, and metastases or recidives have not been noticed. Tumors with a pedicle may be endoscopically removed without complications.

167 patients with Crohn's disease were investigated for joint and spine inflammation. Arthritis was observed in 23 patients (14%), sacroiliitis in 24 (14%), and sacroiliitis in combination with arthritis in 11 patients (7%). 15 patients (9%) had ankylosing spondylitis; 9 of them were HLA-B27 positive (60%). A parallel pattern in the course of bowel disease and joint inflammation was observed in 22 out of 34 patients with arthritis (59%). An association between the localization of Crohn's disease and the type of spondylarthritis could not be demonstrated. Patients with arthritis alone developed erythema nodosum (35%) or aphthous stomatitis more often (21%) than patients without spondylarthritis+ (6% and 12%, respectively). Other extra-intestinal manifestations of Crohn's disease did not reveal any association with the development of spondyloarthritis.

A case report is given of a 24 year old patient who had relapsing massive gastrointestinal bleeding from varices in the duodenum and jejunum, due to occlusion of the mesenterial vein. There is only one similar case described in the literature. 97 patients with varices of the small intestine have been described; in 41 of these cases there was extrahepatic, in 47 intrahepatic portal hypertension. In 60 of the 91 cases varices were found in the duodenum, less frequently in the ileum or jejunum too. In another 10 cases varices had formed around an ileostomy. In 1/3 of all cases abdominal surgery had preceded formation of varices in the small intestine. Pathogenesis, diagnosis and therapy are discussed.

We report about a group of 11 patients with primary lympho- or reticulosarcoma of the stomach in a group of 94 patients with Non-Hodgkin-Lymphomas. There were 5 patients with reticulosarcoma of the stomach among 44 patients with reticularsarcoma (11 percent) and 6 patients with primary lymphosarcoma of the stomach among a total of 50 patients with lymphosarcoma (12 percent). In most instances the diagnosis was made during surgery. At the time of diagnosis only 4 of the 11 patients had Stage IE disease. All patients who received intensive chemotherapy are living. Patients who died during the observation period had reticulosarcomas. They had not received any chemotherapy or treatment was discontinued early for varying reasons. Results are discussed in view of the diagnosis and treatment, suggestions for therapy are made.

Histocompatibility (HLA) antigen phenotypes have been studied in 169 patients with Crohn's disease. The following results could bei shown: HLA-Aw33, -B45 and -Cw3 showed a positive association and HLA-A26, -DR3 and -DRw8 a negative association with Crohn's disease compared to healthy controls. However, when the p-values were corrected by multiplying them by the number of determined antigens per gen-locus, the differences were not significant. Patients with a late onset of the disease (greater than 25 years) showed a statistical significant negative association with HLA-DR3. Numerous studies revealed no significant association between Crohn's disease and HLA-antigens except Smolen et al. (HLA-B12). The significant association of Crohn's disease and HLA-B12 reported by Smolen et al. could be caused by an increased frequency of HLA-B45 as we found in our patients.