Myeloma of the head of the pancreas. A case report

A 45-year-old man was diagnosed with multiple myeloma, IgA-kappa, in 1975. Thirteen years later he presented with obstructive jaundice. Computed tomography (CT) showed a 6-cm mass in the head of the pancreas. Needle aspiration showed myeloma. The jaundice resolved after treatment with radiotherapy. Extraosseous involvement by myeloma is frequently found at autopsy but obstructive jaundice from myeloma of the head of the pancreas is quite rare. This atypical complication of myeloma may be related to the patient's long survival.     

Activation of a Ca2+-dependent K+ current by the oncogenic receptor protein tyrosine kinase v-Fms in mouse fibroblasts

We investigated the effects of the receptor-coupled protein tyrosine kinase (RTK) v-Fms on the membrane current properties of NIH3T3 mouse fibroblasts. We found that v-Fms, the oncogenic variant of the macrophage colony-stimulating factor receptor c-Fms, activates a K⁺ current that is absent in control cells. The activation of the K⁺ current was Ca²⁺-dependent, voltage-independent, and was completely blocked by the K⁺ channel blockers charybdotoxin, margatoxin and iberiotoxin with IC₅₀ values of 3nM, 18 nM and 76nM, respectively. To identify signalling components that mediate the activation of this K⁺ current, NIH3T3 cells that express different mutants of the wildtype v-Fms receptor were examined. Mutation of the binding site for the Ras-GTPase-activating protein led to a complete abolishment of the K⁺ current. A reduction of 76% and 63%, respectively, was observed upon mutation of either of the two binding sites for the growth factor receptor binding protein 2. Mutation of the ATP binding lobe, which disrupts the protein tyrosine kinase activity of v-Fms, led to a 55% reduction of the K⁺ current. Treatment of wild-type v-Fms cells with Clostridium sordellii lethal toxin or a farnesyl protein transferase inhibitor, both known to inhibit the biological function of Ras, reduced the K⁺ current amplitude to 17% and 6% of the control value, respectively. This is the first report showing that an oncogenic RTK can modulate K⁺ channel activity. Our results indicate that this effect is dependent on the binding of certain Ras-regulating proteins to the v-Fms receptor and is not abolished by disruption of its intrinsic protein tyrosine kinase activity. Furthermore, our data suggest that Ras plays a key role for K⁺ channel activation by the oncogenic RTK v-Fms. Received: 19 November 1997 / Accepted: 21 January 1998     

Untersuchung zur Morbidität der indigenen Volksgruppen der Chiquitanos im südlichen Amazonasgebiet

The Chiquitano-tribe lives in the southern Amazonas region in Bolivia, remote from larger towns. A study (n=1514) on morbidity over an one year period (April 1995 till March 1996) and its relation to general and social medicine is given. Most frequently, childreh under 15 years and women in parity age (15–45 years) sought consultation (34,1 %, 42,7 %). Gastrointestinal, respiratoral and gynecological-obstetric diseases were predominant (22,4 %, 16,2 % and 15,7 %). In the dry season, common colds and respiratoral infections represented the major health problem. In the rainy season, infectious diarrhea diseases caused by polluted water as a consequence of extended floods were most frequent. Typical tropical diseases (malaria, Dengue fever, Chagas’ disease, leprosy a.o.) and socially caused diseases (AIDS, dependencies on drugs and alcohol, consequencies of crime) were rarely seen. With respect to severity, 55,8 % of the patients showed mild disorders. More serious diseases were observed in 39, 8 %. 4,6 % of the patients were diagnosed severly ill and needed hospitalization. Epidemiological data on general and social medicine of minorities in developing countries and their actual degree of medical care are important in a shrinking world. The data are useful to estimate medical needs and plan improvements to the health care system especially in rural areas.     

Expression of type-X collagen in osteoarthritis

The present study was undertaken to examine how osteoarthritis affects the expression of type-X collagen, a hypertrophic chondrocyte-specific collagen in articular cartilage. A well characterized sheep polyclonal antiserum, as well as three mouse monoclonal antibodies against canine type-X collagen, was used to immunolocalize type-X collagen in human and canine joints. Its expression in osteoarthritic cartilage was altered in several locations. In the canine osteoarthritic joints, type-X collagen increased in and just above the zone of calcified cartilage and was present diffusely throughout the calcified matrix. In both the human and canine cartilage, type-X collagen was localized around cell clones in the transitional zone of cartilage. This is surprising, since that region of the cartilage does not calcify and one of the proposed roles of type-X collagen is in mineralization. Thus, the osteoarthritic process may damage the matrix in the superficial layer and induce changes leading to the expression of the hypertrophic chondrocyte phenotype.     

A new biscoumarin glucoside ester from Ruta chalepensis cell cultures

The investigation of a plant cell culture of RUTA CHALEPENSIS L. yielded three compounds: isorutarin, rutacridone, and rutarensin, a so far unknown ester of daphnoretin glucoside ("daphnorin"), as well as 3-hydroxy-3-methylglutaric acid.     

Radiologic search for embolized leaflets of prosthetic heart valves: A report of two cases

In a radiologic search for embolized leaflets of Edwards-Duromedics bileaflet valves in 2 patients, the embolized fragments were localized in the iliac vessels using computed tomography. Sonography was successful in one case and standard X-ray films of the abdomen were negative in both cases.In vitro investigations with Björk-Shiley and Edwards-Duromedics leaflets suggested that standard X-ray films of the abdomen and pelvis should be considered as the first investigational technique. If negative, computed tomography of the lower abdomen should be done.     

Plädoyer für die primäre Resektion mit primärer Anastomose bei der komplizierten Sigmadiverticulitis

Zusammenfassung Von 1973 bis 1986 wurden 107 Patienten mit einer komplizierten Sigmadiverticulitis operiert. Es handelte sich um 47 Frauen und 60 Männer bei einem Durchschnittsalter von 62 Jahren. Von 107 Patienten wiesen 14 eine perforierte Diverticulitis mit diffuser eitriger/kotiger Peritonitis auf, 68 Patienten eine perforierte Diverticulitis mit lokalisierter eitriger Peritonitis/paracolischem Absceß und 25 Patienten eine akute phlegmonöse Diverticulitis ohne Perforation. Zusätzliche pathologische Befunde waren: innere Fisteln (13 Patienten), nekrotisierende Fasciitis (3 Patienten), Stenose mit Ileus (3 Patienten) und synchrone Carcinome (7 Patienten). Die Gesamtletalität der 107 Patienten betrug 9,3% (=10 Patienten), die Morbidität der 97 überlebenden Patienten 34,0% (= 33 Patienten). Die Letalität bei 14 Patienten mit perforierter Diverticulitis und diffuser eitriger/kotiger Peritonitis lag bei 50%, die der 68 Patienten mit perforierter Diverticulitis und lokaler eitriger Peritonitis/ paracolischem Absceß bei 4,4%, die der 25 Patienten mit akuter phlegmonöser Diverticulitis ohne Perforation bei 0%. Von den 10 Patienten verstarben 7 bei Operation ihrer perforierten Diverticulitis mit diffuser eitriger Peritonitis, 1 (5) nach primärer Resektion mit primärer Anastomose, 3 (5) nach Operation nach Hartmann, 3 (4) nach alleiniger Anlage einer Colostomie. Bei Operation der perforierten Diverticulitis mit lokaler Peritonitis verstarben 3 Patienten, 2 (6) nach Operation nach Hartman und 1 (5) nach alleiniger Anlage einer Colostomie. Trotz einer hohen Zunahme der Zahl primärer Resektionen mit primärer Anasto mose im Zeitraum 1980–1986 ergab sich im Vergleich zum 7-Jahresabschnitt 1973–1979 ein Rückgang der Letalität von 35,7% auf 0% bei dieser Operation. Ihre Anwendung ist auch gerechtfertigt bei der perforierten Diverticulitis mit lokaler wie diffus eitriger oder kotiger Peritonitis.

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Primary resection with primary anastomosis in complicated diverticulitis of the sigma

Summary Of the 107 patients with complicated diverticulitis operated from 1973–1986 47 were females and 60 males. In 14 of the 107 patients a perforated diverticulitis with diffuse purulent/faecal peritonitis was found, a perforated diverticulitis with localized purulent peritonitis/paracolic abscess in 68 patients and an acute phlegmonous diverticulitis without perforation in 25 patients. Additional pathologic findings were internal fistulae (13 patients), necrotizing fasciitis (3 patients), obstruction (3 patients) and synchronous carcinoma (7 patients). The overall mortality of the 107 patients was 9.3 % (=10 patients) and the morbidity of the 97 survivors 34% (=33 patients). The mortality of the 1.4 patients with perforated diverticulitis and diffuse purulent peritonitis was 50%, of the 68 patients with perforated diverticulitis and localized purulent peritonitis 4.4% and of the 25 patients with acute phlegmonous diverticulitis 0%. Seven of the 10 patients died after operation of the perforated diverticulitis with diffuse purulent peritonitis — 1 (5) after primary resection with primary anastomosis, 3 (5) after Hartmann procedure, 3 (4) after loop colostomy alone. Three patients died after operation of the perforated diverticulitis with localized purulent peritonitis — 2 (6) after Hartmann procedure, 1 (5) after loop colostomy alone. In spite of forcing the primary resection with primary anastomosis in the years from 1980–1986 the mortality decreased for these operations from 35.7% in 1973–1979 to 0% in 1980–1986. The indication of primary resection with primary anas tomosis is justified also for perforated diverticulitis with localized and diffuse peritonitis.

Auszugsweise vorgetragen auf dem Symposium Entzündliche Darmerkrankungen der Medizinischen Akademie Carl Gustav Carus, Dresden, 20. November 1987     

Inflammatory regulation of extracellular matrix remodeling in calcific aortic valve stenosis.

BACKGROUND: Calcific aortic stenosis (AS), the most frequent heart valve disorder in developed countries, leads to the calcification and fibrous thickening of the valve. While several studies have addressed the process of valvular calcification, the molecular pathomechanisms of the extensive matrix remodeling remain unclear. Because inflammation is present in stenotic valves, we hypothesized that the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) might influence cell proliferation and regulate the expression and activation of matrix metalloproteinases (MMPs)--enzymes that are thought to be involved in calcific AS. METHODS: Immunohistochemistry for leukocytes, TNFalpha, MMP-1, and the endogenous MMP inhibitor tissue inhibitor of metalloproteinase (TIMP)-1 was performed on human stenotic (n = 19) and control (n = 8) valves. Primary cultures of human aortic valve myofibroblasts were incubated with and without TNFalpha, and cell proliferation was assessed. The expression and activation of MMP-1 were detected by Western blotting and a specific MMP-1 activity assay. RESULTS: Control valves showed scattered macrophages and low expression of TNFalpha, MMP-1, and TIMP-1. In stenotic valves, leukocyte infiltration and a strong, colocalized expression of TNFalpha and MMP-1 were present, while TIMP-1 remained unchanged. Double-label immunofluorescence localized TNFalpha mainly to macrophages. In cultured human aortic valve myofibroblasts, TNFalpha stimulated proliferation and induced a time-dependent increase in MMP-1 expression and activation, while TIMP-1 remained unchanged. CONCLUSION: The results indicate that matrix remodeling in calcific AS involves the expression and activation of MMPs. Activated leukocytes, by the secretion of TNFalpha, may stimulate valvular myofibroblasts to proliferate and express MMPs, thus regulating actively the matrix remodeling in calcific AS.     

Identification of a naturally processed cyclin D1 T-helper epitope by a novel combination of HLA class II targeting and differential mass spectrometry

T-helper (Th) cells play an important role in orchestrating the effector function of CTL in anti-tumor immunity. However, only a limited number of Th cell epitopes has been characterized. Here we describe a novel approach for identifying naturally processed and presented peptides derived from chosen antigens. This method combines a transfection step of antigen-presenting cells with a vector encoding a fusion protein between the Ii chain and the antigen of interest, elution of the HLA-bound peptides and identification of the antigen-derived peptides by mass spectrometric comparison to the non-transfected cells. In vitro-stimulated Th cells against the identified peptide of interest specifically recognize transfectants overexpressing the cognate antigen. Using this approach, we were able to identify the HLA-DR4-restricted Th cell epitope NPPSMVAAGSVVAAV derived from cyclin D1, which is frequently overexpressed in tumors. This method will help in identifying peptide candidates for vaccination studies for tumor immunotherapy.     

Is one assessment enough? Patterns of helping alliance development and outcome

Early therapeutic alliance is usually measured by the rating of a single session (between the third and the fifth sessions). However, there is a strong argument in favor of viewing early alliance as a developing process. This study examined the relationship between patient's rating of the helping alliance (HAq) at each session and therapy outcome. This comparison was repeated using patterns of alliance over the course of treatment. Patterns of therapeutic alliance development were detected by clustering ratings of a sample of N = 70 outpatients across four sessions of very brief psychotherapeutic intervention. Cluster analysis revealed two main patterns (shapes) of alliance development: (i) stable alliance, and (ii) linear growth pattern. These patterns are more predictive of symptom improvement and social adjustment than single ratings, whereas single ratings measuring the strength of alliance are more correlated with patient's satisfaction. Copyright © 2004 John Wiley & Sons, Ltd.