Tumour budding, uPA and PAI-1 are associated with aggressive behaviour in colon cancer.

AIMS: The proteases PAI-1 and uPA play a major role in extracellular matrix degradation, which facilitates tumour progression. Tumour budding is a histomorphological expression of enhanced tumour cell migration. MATERIALS AND METHODS: To investigate their prognostic value for and correlation with colon cancer, a prospective study was performed. We analysed tissue levels of uPA and PAI-1 of 55 colon cancer tumours employing a commercially available enzyme-linked immunosorbent assay (ELISA). Tumour budding was analysed on cytokeratin-stained slides. RESULTS: There was a strong correlation between uPA and tumour budding (R = 0.440; P < 0.001). uPA levels were increased in high grade tumours, whereas PAI-1 was elevated in cases with venous invasion (P = 0.004 and P = 0.028). PAI-1 values and tumour budding are associated significantly with the occurrence of distant metastases (P < 0.001 and P = 0.034, respectively). Tumour budding was significantly associated with lymph node metastases (P = 0.034). Multivariate analysis revealed PAI-1 and lymph node metastases to be independently predictive of distant metastases (P = 0.007 and P = 0.004, respectively). CONCLUSIONS: The results of our study show that tumour budding and the plasmin/plasminogen system are related. PAI-1 was independently predictive for the occurrence of distant metastasis.

[Impending Coumarin-necrosis in a patient with heterozygous protein C deficiency type I]. / Drohende Cumarinnekrose bei einer 24-jährigen Patientin mit stattgehabter Beinvenenthrombose.

Painful pink or magenta colored skin lesions characterized by a clear line of demarcation between the affected area and surrounding tissue appearing under therapy with coumarins may be a sign for evolving coumarin-necrosis. Immediate treatment with a protein C preparation in patients with protein C deficiency can prevent necrosis.

[Meningitis caused by Streptococcus suis]. / Bakterielle Meningitis durch Streptococcus suis.

HISTORY AND ADMISSION FINDINGS: A 42-year-old man was admitted to hospital because of headache and fever for two days and showing signs of meningism. As a butcher he had had frequent cuts on his hands and forearms. INVESTIGATIONS AND DIAGNOSIS: Analysis of the cerebrospinal fluid revealed an elevated leukocyte count (81% segmented neutrophils). Large numbers of Gram-positive bacteria were found in both cerebrospinal fluid and blood culture, which were subsequently identified as Streptococcus suis (S. suis) by biochemical methods. The hypothesis of bacterial meningitis was thus confirmed. TREATMENT AND CLINICAL COURSE: The patient was treated with ampicillin, initially combined with ceftriaxone. Hearing impairment and vestibular dysfunction - a frequent complication after infection with S. suis - were observed as sequelae, indicating involvement of the vestibulocochlear nerve. CONCLUSION: Infections caused by S. suis are rare in Europe but must be taken into account if an occupational exposition to pigs is established.

[Interdisciplinary diagnostics in the outpatient treatment department of an environmental medical centre - report on experience with 400 patients]. / Interdisziplinäre Diagnostik in der umweltmedizinischen Ambulanz - ein Erfahrungsbericht über 400 Patienten.

The medical diagnostics of 400 patients of an interdisciplinary environmental medical centre is presented. The basic diagnostics included a special environmental medical history using a questionnaire, physical examination, allergological examinations and human biomonitoring. The latter was carried out in order to quantify the internal exposure to environmental pollutants. The main focus was on the differential diagnostics which was supported by special medical divisions of the hospital. Allergic illnesses as well as results of human biomonitoring exceeding the reference ranges were found frequently. Unfortunately a link between external exposure, internal dose and symptoms can hardly be established in environmental medicine. However, in several cases we found a considerably increased internal exposure which allowed to identify the sources of exposure (for example, usage of dichlorobenzene, permethrin, pentachlorophenol). Eliminating the sources obviously improved the health status of some of the patients concerned.

[Pyrethroid exposure following indoor treatments with a dog flea powder]. / Pyrethroidbelastung durch Parasitenprophylaxe beim Hund.

UNLABELLED: Pyrethroid exposure following indoor treatments with a dog flea powder. HISTORY: A 42 year old woman reported hair loss, gastrointestinal and non-specific symptoms. The patient has lived in a council flat and kept a dog who had been regularly treated with pyrethroid containing flea powder. INVESTIGATIONS: The biological monitoring of pyrethroid meta-bolites in urine was performed using gas chromatography-mass spectrometry. The values at admission and follow-up after 4 weeks were highly elevated. Inspection of the flat revealed a humid and cramped dwelling. TREATMENT: We recommended redevelopment and cleaning of the dwelling and the avoidance of ectoparasiticide use. CONCLUSION: To our knowledge this is the first documented case of high indoor pyrethroid exposure following the use of ectoparasiticides with domestic animals. Pyrethroids can cause neurotoxic symptoms and skin irritation. There are few data concerning chronic effects. The causal connection between pyrethroid exposure and symptoms remains unclear and poses a great problem in environmental medicine.

Tumor cell contamination of peripheral blood stem cell transplants and bone marrow in high-risk breast cancer patients.

Twenty-one high-risk patients with primary stage II/III breast cancer were treated with high-dose chemotherapy comprising etoposide, ifosfamide, carboplatin and epirubicin (VIC-E). Tumor cells of epithelial origin were analyzed using the monoclonal antibodies CK2 (IgG1) and A45-B/B3 (IgG1) against cytokeratin (CK) components in bone marrow (BM) aspirates prior to chemotherapy, and in peripheral blood stem cell transplants (PBSCT). They were separated after the first (21/21 patients) and the second cycle (16/21 patients) of induction chemotherapy with VIP-E (etoposide, ifosfamide, cisplatin, epirubicin). Preliminary results showed CK positive tumor cells in 40% (14/35) of the analyzed transplants. In 7/12 (58.3%) patients, CK positive tumor cells were detectable in BM prior to treatment. Sixteen patients were separated after the 1st and 2nd cycle of VIP-E. PBSCT of 14/16 patients were assessable for presence of CK positive tumor cells. Our preliminary results demonstrate a lower tumor cell contamination of PBSCT separated after the 2nd cycle of induction therapy (14.3%) compared to contamination after the first induction therapy (64.3%). To date, 4/21 patients have experienced a relapse, and three of these patients had tumor cell positive transplants. Due to the small patient number only a trend towards a superior relapse-free survival in the patient group with CK negative transplants can be shown by Kaplan-Meier analysis.

[The current status of vaccination and antibiotic prophylaxis in splenectomy. I: Adults]. / Standortbestimmung der Impf- und Antibioticaprophylaxe bei Splenektomie. Teil I: Erwachsene.

The prevention of severe late postsplenectomy infection by vaccination and antibiotic prophylaxis is controversial. This paper reviews the literature and presents a protocol for postsplenectomy adults. Prophylaxis should be adapted to the underlying disease. Every patient has to be informed about the consequences of splenectomy. Depending on the underlying disease, vaccination is recommended against pneumococci, Hemophilus influenzae and Neisseria meningitidis. Long-term antibiotic prophylaxis is not advised in adults.

Specific and sensitive two-step polymerase chain reaction assay for the detection of Salmonella species.

A polymerase chain reaction (PCR) assay was applied for the selective amplification of a characteristic sequence within a Salmonella-specific chromosomal fragment. A two-temperature PCR cycle enhanced both the speed and overall sensitivity of the amplification procedure. Twenty-one well-characterized Salmonella strains and a number of non-Salmonella strains were tested. With the exception of the rarely isolated Salmonella arizonae strain, the PCR-based approach enabled the specific identification of Salmonella with a detection limit of 10(3) organisms. In combination with a nested PCR assay, as few as ten organisms were detectable. Specificity was demonstrated as no distinct amplification products were detectable with any of the tested non-Salmonella strains. With a pre-enrichment step using paramagnetic anti-Salmonella beads, an increase in sensitivity was observed in the case of clinical samples while the amplification process was not influenced.

DNA fingerprinting by pulsed-field gel electrophoresis to investigate a nosocomial pneumonia caused by Legionella bozemanii serogroup 1.

We typed 18 isolates of Legionella bozemanii obtained from clinical and environmental sources by pulsed-field gel electrophoresis. Each of the unrelated strains showed individual restriction patterns of the genomic DNA when either the SfiI or NotI restriction enzyme was used. One strain isolated from a patient with nosocomial legionellosis and two strains from the corresponding hospital water supply were indistinguishable, arguing for a transmission of L. bozemanii from the water supply to the patient. In conclusion, macrorestriction analysis is a valuable tool for studies of the molecular epidemiology of L. bozemanii.

The influence of the pH-value on the growth of Brevibacterium epidermidis in continuous culture.

Brevibacterium epidermidis is a major component of the bacterial flora of certain skin surface biotopes, characterized by a comparatively high pH-value. The presence of Brevibacterium epidermidis seems to be linked to the production of malodour. Skin surface pH has been found to be a major factor of bacterial growth on the skin. In order to find out if this might also apply to Brevibacterium epidermidis, this microorganism was grown in vitro in continuous culture using a chemostat. Specific growth rate and density of colony forming units were well correlated. While the organism grew readily from pH 5.5 to 8.5, this was not the case with a pH of 5.0. Thus pH-shifts induced by cosmetic procedures can only prevent unpleasant body odour due to abundant growth of bacteria if the pH-value is decreased to 5.0 or less.

[Eradication of Legionella from warm water systems--documentation of our own experiences with thermal disinfection]. / Sanierung von Warmwassersystemen mit Legionellenbefall--Dokumentation eigener Erfahrungen mit thermischer Desinfektion.

A nosocomial case of Legionellosis in a recently built hospital was the reason for an investigation and thermal disinfection of the complete warm water distribution system. Furthermore weak points in the tubing of the warm water system, which promoted the contamination of potable water, were eliminated as far as technically possible. A lasting reduction of the numbers of Legionella spp. isolated could be measured (factor 10-1000), but a complete decontamination of the warm water distribution system was not possible. As Legionella spp. may cause serious infections in immunodeficient patients, additional measures for the disinfection of the hospital water distribution system must be taken into consideration.

[Severe legionellosis after abuse of anti-inflammatory drugs--diagnostic and intensive care aspects based on a case report]. / Schwere Legionellose nach Antiphlogistika-Abusus--diagnostische und intensivtherapeutische Aspekte anhand einer Kasuistik.

Legionella infections are getting increasingly important as causes of severe pneumonias or of acute respiratory insufficiency. Consumptive or immunosuppressive underlying diseases such as diabetes mellitus, cardiac insufficiency, alcohol-induced liver damage, malignant tumours or drug-induced immunosuppression after organ transplantation, are among the risk factors. Diagnosis is based on direct identification of the pathogen from body secretions by means of direct immunofluorescence. The serological immunoresponse often takes place long after outbreak of the disease or fails entirely to appear and is therefore only suitable for retrospective confirmation. Therapy of choice is an intravenous administration of erythromycin. There are now increasing pointers to the efficiency of fluoroquinolone antibiotics, such as ciprofloxacin. We report on the course of a severe case of legionnaire's disease with multiple organ failure occurring in a patient after bone marrow depression induced by anti-inflammatory drugs. Treatment erythromycin resulted in a marked cholestasis, so that antibiotic treatment was changed to ciprofloxacin. This therapy as well as the supportive intensive-care treatment eventually led to the patient's complete recovery. Based on the case report, fundamental aspects of diagnostics, antibiotic treatment, intensive-care treatment and prognosis of severe cases of legionellosis are discussed.

Isolation of a Legionella pneumophila strain serologically distinguishable from all known serogroups.

A Legionella pneumophila strain (Jena-1) was isolated from a water sample collected from the hot water system of a scientific institution in Jena, Germany. Protein profile, ubiquinone and fatty acid content of the outer membrane were in accordance with those described for other Legionella pneumophila serogroups. DNA extracted from strain Jena-1 gave a positive amplification by using an L. pneumophila (mip)-specific commercially available PCR-kit confirming that the isolate belonged to the species L. pneumophila. Strain Jena-1 reacted with a monoclonal antibody specific for the major outer membrane protein of the species L. pneumophila and another one recognizing a lipopolysaccharide epitope of L. pneumophila serogroups 2-6, 8-10, and 12-15. Cross-absorption studies using absorbed and unabsorbed rabbit antisera to serogroups 1-15 and the newly isolated strain showed that strain Jena-1 cross-reacted mainly with serogroup 4, and to a lesser extent, with serogroups 5, 8, and 10. These cross-reactions could be removed by cross-absorption without significant effects on the homologous titres. It is concluded that strain Jena-1 represents a new serogroup of Legionella pneumophila.

The production of porphyrins from delta-aminolaevulinic acid by Haemophilus parainfluenzae.

Porphyrin production by the haemin-independent Haemophilus parainfluenzae in the diagnostic porphyrin test, which determines the X-factor requirement in Haemophilus spp., was analysed quantitatively by applying modern high-performance liquid chromatographic (HPLC) methods. Ion-pair reversed-phase HPLC enabled the simultaneous separation of all porphyrin intermediates and their isomers of haem biosynthesis produced by the bacteria. The pH-dependence of porphyrin production and the respective composition of the porphyrins within the bacterial cells and in the supernate were investigated. A pH optimum of 6.9-8.0 for the production of porphyrins was found and there were marked differences in the porphyrin profiles at different pH values.

[Effects of different methods of tooth resection in suckling piglets]. / Auswirkungen verschiedener Methoden der Zahnresektion beim Saugferkel.

Epizootic examinations were made on 796 newborn piglets to test the consequences of the resection of a piglet's canine and lateral incisor teeth on its first day of life. As a comparative examination the resection was carried out with side-cutter pliers or with the teeth grinder PIGMATIC 110. A third group of piglets was not treated. Histological, radiographic and bacteriological examinations were made of 10 piglets--in each case with piglets with the resection with side-cutter pliers or with the teeth grinder. 48% of ground teeth reacted with an inflammation of the pulp. The clipping of the crown of teeth with side-cutter pliers caused pulpitis in 92% of the teeth. Inflammation of the gingiva could almost only be seen around clipped teeth. Splinters only occurred with teeth which had been clipped with side-cutter pliers. Gingivitis and pulpitis extended along the splinters to the bottom of the root. Bites among the litter mates were more frequent in the group of piglets whose teeth had not been treated than in the group of piglets with resected teeth. Compared to the grinding or the clipping of needle teeth, bites to the sow's udder were much more frequent if the resection had been omitted. During the whole period of examination the mortality of piglets was at its lowest in the group of piglets with clipped teeth. The development of grinding instruments for the resection of needle teeth presents a method which reduces the negative consequences of the conventional resection with side-cutter pliers and shows clearly the advantages of resection. In terms of animal welfare, teeth resection is an amputation and therefore every case requires veterinary justification.

Nosocomial outbreak of legionellosis in a rehabilitation center. Demonstration of potable water as a source.

Ten patients from a rehabilitation center were admitted to hospital with serious respiratory infections within ten weeks. An outbreak of Legionnaire's disease was suspected based on the epidemic and atypical manifestation of pneumonia and could be proven microbiologically. Pulmonary and extrapulmonary complications included respiratory failure, lung abscess, transitory renal impairment in five patients and acute renal failure requiring dialysis in one, tetraparesis caused by peripheral neuropathy and acute psychosis. Three patients died despite immediate institution of therapy with erythromycin. Legionella pneumophila serogroup 1 subtype Pontiac was isolated from a bronchial lavage sample of one patient and from the water supply of the rehabilitation center. Monoclonal antibody subtyping and restriction endonuclease analysis were performed on both environmental and patient isolates. Potable water was identified as the source of the outbreak based on identical patterns on restriction endonuclease analysis. Despite thermic and chemical disinfection with chlorination (up to 15 ppm) in the rehabilitation clinic, an eleventh case of Legionnaire's disease was detected 11 months later.

[Case study of a Legionella epidemic in a rehabilitation clinic]. / Kasuistik einer Legionellen-Epidemie in einer Rehabilitationsklinik.

A series of nosocomial Legionella infections in a rehabilitation center is reported. In a three months period a total of 10 pneumonias with 3 deaths occurred (8 patients, 1 companion, 1 staff member). Serologic analysis proved additional Legionella infections within the nursing staff. The warm-water system was proved to be the source of infection by isolating Legionella pneumophila serogroup 1 subtype Pontiac both in warm-water and patients samples. The air conditioning system could not be ruled out as another (secondary) route of exposure because of shortcomings in construction. Conclusions about prevention and the course of the disease are discussed and standards for warm-water and air conditioning systems are proposed.