Comparison of germ cell mutagenicity in male CYP2E1-null and wild-type mice treated with acrylamide: evidence supporting a glycidamide-mediated effect.

Acrylamide is an animal carcinogen and probable human carcinogen present in appreciable amounts in heated carbohydrate-rich foodstuffs. It is also a germ cell mutagen, inducing dominant lethal mutations and heritable chromosomal translocations in postmeiotic sperm of treated mice. Acrylamide's affinity for male germ cells has sometimes been overlooked in assessing its toxicity and defining human health risks. Previous investigations of acrylamide's germ cell activity in mice showed stronger effects after repeated administration of low doses compared with a single high dose, suggesting the possible involvement of a stable metabolite. A key oxidative metabolite of acrylamide is the epoxide glycidamide, generated by cytochrome P4502E1 (CYP2E1). To explore the role of CYP2E1 metabolism in the germ cell mutagenicity of acrylamide, CYP2E1-null and wild-type male mice were treated by intraperitoneal injection with 0, 12.5, 25, or 50 mg acrylamide (5 ml saline)(-1) kg(-1) day(-1) for 5 consecutive days. At defined times after exposure, males were mated to untreated B6C3F1 females. Females were killed in late gestation and uterine contents were examined. Dose-related increases in resorption moles (chromosomally aberrant embryos) and decreases in the numbers of pregnant females and the proportion of living fetuses were seen in females mated to acrylamide-treated wild-type mice. No changes in any fertility parameters were seen in females mated to acrylamide-treated CYP2E1-null mice. Our results constitute the first unequivocal demonstration that acrylamide-induced germ cell mutations in male mice require CYP2E1-mediated epoxidation of acrylamide. Thus, CYP2E1 polymorphisms in human populations, resulting in variable enzyme metabolic activities, may produce differential susceptibilities to acrylamide toxicities.

Antibody levels against Chlamydia pneumoniae and outcome of roxithromycin therapy in patients with acute myocardial infarction. Results from a sub-study of the randomised Antibiotic Therapy in Acute Myocardial Infarction (ANTIBIO) trial.

BACKGROUND: Results of studies concerning prevention of cardiovascular disease by treatment with macrolide antibiotics targeting C. pneumoniae infection are still controversial. This study describes the results of different tests for infection with C. pneumoniae as well as the effect of treatment with roxithromycin in patients with acute myocardial infarction (AMI) in relation to their serostatus against C. pneumoniae. METHODS: We analysed blood of 160 patients who came from the ANTIBIOtic therapy after an AMI ( ANTIBIO-) study, a prospective, randomised, placebo-controlled, double-blind study to investigate the effect of roxithromycin 300 mg/OD for 6 weeks in patients with an AMI. Anti- Chlamydia IgG-, IgA-, and IgM-antibodies of these patients were analysed by means of different test systems. RESULTS: There was a good correlation between the two IgG and IgA methods (r = 0.900, p < 0.001 and r = 0.878, p < 0.001, respectively), but marked differences in the prevalence of positive tests. This resulted in only moderate concordance values, as expressed by the Kappa coefficients, for IgG kappa = 0.611 (95% CI = 0.498-0.724, p < 0.001) and for IgA kappa = 0.431 (95% CI: 0.322-0.540, p < 0.001). No significant association between positive C. pneumonia titers and the combined clinical endpoint during the 12 month follow-up could be found. In all test systems used, patients with positive anti- C. pneumoniae titers did not benefit from roxithromycin therapy (p = ns). CONCLUSION: Depending on the test system used, there are large differences in the prevalence of anti- C. pneumoniae seropositive patients. Clinical events during the 12 month follow-up after AMI did not depend on serostatus against C. pneumoniae and treatment with roxithromycin did not influence these events, independently of the serostatus against C. pneumoniae. However, the power of this subgroup analysis was low to detect small but significant differences.

[Heavy diarrhea by low malignant B cell lymphoma]. / Schwere Durchfälle bei niedrig malignem B-Zell-Lymphom.

A 52-year old female presented with a low, malignant centroblastic-centrocytic lymphoma. After splenectomy and under steroid therapy it came to the eruption of a latent Strongyloides stercoralis infection, which the patient had presumably been suffering from for several years. Due to the immunodeficient condition and under continued steroid therapy even three courses of high dose anthelmintic therapy could not eradicate the parasites. The patient died of fulminant sepsis.

Inhibition of lipase activity in antibiotic-resistant propionibacterium acnes strains.

BACKGROUND AND OBJECTIVE: Erythromycin-sensitive and/or clindamycin-sensitive strains of Propionibacterium acnes show a reduced lipase production at levels below the minimal growth-inhibitory concentration (MIC). The objective of this study was to determine whether erythromycin and clindamycin concentrations far below the MIC inhibit lipase production in P. acnes strains resistant to these antibiotics. METHODS: Of 42 P. acnes strains, 10 showed an MIC >256 micro g/ml for erythromycin. Two strains showed MICs of 0.19 and 0.25 micro g/ml, while the MIC of the remaining strains was 256 micro g/ml were also tested for lipase inhibition by clindamycin. While this method fails to differentiate between inhibition of lipase production and inhibition of lipase activity, the absence of inhibition of lipase activity rules out inhibition of lipase production. RESULTS: Inhibition of lipolysis by sub-MIC concentrations was demonstrated only for clindamycin in 3 P. acnes strains. However, lipase inhibition was seen only at the dilution level immediately below the MIC. CONCLUSIONS: Resistant P. acnes strains with high erythromycin and/or clindamycin MICs can be ruled out to show in vitro inhibition of lipase production at antibiotic concentrations far below the MIC.

In vitro antimicrobial susceptibility of oral strains of Actinobacillus actinomycetemcomitans to seven antibiotics.

BACKGROUND/AIMS: Periodontal infections with Actinobacillus actinomycetemcomitans seem to be refractory to conventional therapy. The aim of the present study was to test the in vitro susceptibilities of A. actinomycetemcomitans strains to a panel of seven orally administrable antibiotics. METHODS: A total of 60 isolates of A. actinomycetemcomitans recovered from 43 individuals with gingivitis or periodontitis were tested. In addition, laboratory strains UP-6 and JP2 were analysed. The E-test was employed in order to determine minimal inhibitory concentrations (MIC) of antibiotics ampicillin/sulbactam, roxithromycin, azithromycin, doxycycline, metronidazole, ciprofloxacin, and moxifloxacin. RESULTS: A. actinomycetemcomitans was highly susceptible to both fluoro-quinolones (MIC90 of 0.006 microgram/mL of ciprofloxacin and 0.032 microgram/mL of moxifloxacin). Good susceptibilities were found for ampicillin/sulbactam and doxycycline (MIC90 of 0.75 microgram/mL and 1 microgram/mL, respectively), and moderate susceptibilities for azithromycin (MIC90 of 3 microgram/mL). Most strains were resistant to metronidazole and roxithromycin. Cluster analysis revealed two larger clusters of A. actinomycetemcomitans strains with the smaller cluster assembling isolates with significantly higher MICs of most antibiotics. CONCLUSIONS: Due to reported favourable pharmacokinetics, the fluoro-quinolone moxifloxacin appeared to be a promising candidate for adjunctive systemic antibiotic therapy in periodontal infections with A. actinomycetemcomitans.

[Gastroenteritis due to Plesiomonas shigelloides--rare cases in the Western world]. / Plesiomonas-shigelloides-induzierte Gastroenteritiden--seltene Fälle in der westlichen Welt.

BACKGROUND: Plesiomonas shigelloides is a common pathogen in tropical regions, whereas it is rarely isolated in temperate climates. It is most often found in surface water and fish. During the last 10 years it was found to cause gastroenteritis 6 times in Ludwigshafen. Not all of these patients reported a trip to foreign countries. CASE REPORT: A 54-year-old male patient was hospitalized after a trip to Malaysia with strong greenish watery diarrhea and chills. On physical examination we saw a dehydrated patient in severely reduced general condition. The stool frequency was 30/d. The laboratory examinations only showed elevated parameters of inflammation. Plesiomonas shigelloides was cultivated in the stool cultures. With appropriate substitution of fluid and electrolytes, and antidiarrheal therapy the patient resumed a normal diet without any complications. Three days later his bowel movements were normal and his general condition was greatly improved. We withheld antibiotic therapy because of the noncomplicated course of illness. CONCLUSION: In Germany infections with Plesiomonas shigelloides are rare, an increase is observed because of increasing tourism to tropical regions. The course of infection is sometimes asymptomatic, but usually patients develop an acute gastroenteritis. Especially immunocompromised patients can show serious courses of infection. Plesiomonas shigelloides should be included in the differential diagnosis of acute gastroenteritis after journeys to tropical regions. Some of our patients, however, denied traveling to tropical regions. They also denied consuming seafood, which indicates a risk of infection in Germany. Still an infection with Plesiomonas shigelloides seems to be rare in northern European countries.

In-vitro and in-vivo efficacy of zinc acetate against propionibacteria alone and in combination with erythromycin.

Some studies have been published about the in vitro activity of zinc acetate (ZA), erythromycin (E) and their combination (ZA/E) against Propionibacterium spp., especially erythromycin resistant strains. The efficacy of topical ZA/E combination has been reported as well, but a comparison to ZA monotherapy is missing. Therefore, the MIC values of ZA, E and the ZA/E combination were determined for 15 erythromycin-resistant and 12 erythromycin-sensitive Propionibacterium strains using the agar dilution method and the checkerboard technique. Furthermore, the antimicrobial efficacy of ZA (1.2%) vs. the ZA/E (1.2%/4%) combination in an alcoholic solution was tested in a 7-day treatment administered to 32 acne patients. The MIC 100 for ZA was 1024 micrograms ZA/ml for both, erythromycin resistant and erythromycin sensitive Propionibacterium strains. The ZA, as well as the ZA/E solution showed efficacy reducing both the Propionibacterium spp., and the Micrococcaceae in the sebaceous gland infundibula of acne patients. There was no significant difference between the two treatments. As the MIC 100 of ZA/E was equal to the MIC 100 of ZA, the decrease of the erythromycin MIC of the ZA/E combination in erythromycin-resistant strains may be partly attributed to the addition of ZA to E. The in vivo antibacterial efficacy on 32 acne patients supports the hypothesis that the antibacterial effect of ZA/E in short-term treatment can be mostly attributed to ZA.

In Vitro activity of 6 antimicrobials against propionibacteria isolates from untreated acne papulopustulosa.

In the present study, MIC values of 6 antibiotics were determined for 70 Propionibacterium acnes and 13 P.granulosum strains from 71 untreated acne patients using the agar dilution method. The interpretation of in vitro results is difficult because there are only poor data about the concentrations of antibiotics achievable in the sebaceous gland infundibulum. Based on breakpoint concentrations according to DIN 58,944, no resistance was found against chlortetracycline, doxycycline, minocycline, and chloramphenicol. In contrast, 11% of the P.acnes and 31% of the P.granulosum strains were not susceptible in vitro to erythromycin at a breakpoint concentration of 4 micrograms/ml. The present study shows that these strains are not suppressed even at higher erythromycin concentrations up to 256 micrograms/ml. Data from the literature reporting ineffective treatment of patients carrying erythromycin-resistant P.acnes strains may be explained by our study. Concerning clindamycin, resistance was found in only 6.8% of P.acnes and in 0% of the P.granulosum strains. Since sensitivity was seen in 100% of the strains already at a concentration of 16 micrograms/ml, a therapeutic effect may be possible.

Eradication of MRSA from carriers by means of whole-body washing with an antiseptic in combination with mupirocin nasal ointment.

Patients who are infected or colonised by MRSA should be isolated. However, isolation is very costly in terms of time and work. In order to shorten the period of isolation, attempts are being made to eradicate this organism from patients by means of whole-body washing in addition to nasal mupirocin treatment. The effectiveness of such washes has not yet been adequately confirmed by studies. From September 1997 to August 1998, therefore, in a clinical trial of MRSA eradication, 28 patients were washed for a period of five days with a 1:1 diluted preparation based on octenidine dihydrochloride. At the same time, the nose was treated with mupirocin. Before washing was begun, on day 4 during washing and on days 1, 4 and 7 after washing was completed, smears were taken from each patient from the nose, pharynx, forehead hairline, groin, axilla and wounds, and in the case of women from the sub-mammary area. Elimination of the MRSA was achieved in 21 out of 28 cases; in four cases the washing was discontinued on account of skin redness, in three cases no elimination could be achieved during the control period. In order to ensure the success of eradication and to minimise skin reactions due to the washing, the wash procedure must be standardised, and decontamination controlled microbiologically. The study confirms that MRSA can be eradicated by means of washing with an antiseptic combined with mupirocin treatment.

Antibacterial and sebosuppressive efficacy of a combination of chloramphenicol and pale sulfonated shale oil. Multicentre, randomized, vehicle-controlled, double-blind study on 91 acne patients with acne papulopustulosa (Plewig and Kligman's grade II-III).

In a 3-armed, multicentre, randomized, double-blind, vehicle-controlled study involving 91 patients with acne papulopustulosa, Plewig's grade II-III, evidence could be provided of a significant reduction of the propionibacteria as well as a subosuppressive effect (squalene reduction) under a combination of 1% chloramphenicol (CAS 56-75-7) and 0.5% pale sulfonated shale oil versus the alcoholic vehicle (1-2 ml twice daily). Likewise, monotherapy with chloramphenicol resulted in a significant reduction in bacteria compared to the vehicle. The combination therapy was superior to the monotherapy with regard to the sebosuppressive effects. Based on a kinetics test carried out for a total of 2 h, a clinically relevant percutaneous absorption of chloramphenicol was ruled out. The chloramphenicol serum level was between < 5.0 microgram/l to 180 microgram/l (average 25 micogram/l). This is important because with systemic application (peroral, i.v.), the therapeutic chloramphenicol level is > 25 mg/l (25,000 microgram 1). None of the blood count and serum parameters were pathologically changed in a clinically relevant way before and after the therapy. An induction of resistance against chloramphenicol in the propionibacteria could be excluded. No adverse events and side effects occurred. The topical therapy of acne papulopustulosa with chloramphenicol as a monosubstance or in combination with pale sulfonated shale oil represents an effective and safe local antibiotic treatment possibility.

[Specificity of first and second generation HIV-1 antibody screening tests]. / Spezifität von HIV-1-Antikörper-Suchtests der "ersten und zweiten Generation".

Among 9867 sera tested between January and April 1987 by Abbott HTLV-III EIA (cell culture-derived antigen) 155 reacted repeatedly positive. 22% of these could not be confirmed, while 77% could be confirmed by other tests. The results of 2 sera remained equivocal. Subsequently Abbott recombinant HTLV-III EIA was used and until August of the same year 184 out of 11508 sera gave reproducible positive results. 12% of these could not be confirmed, while 86% could be confirmed. The results of 3 sera remained equivocal. False positive results were found in 0.34% of all sera examined by the test of the first generation, whereas the percentage in the second generation test was 0.19. Despite the higher specificity of the ELISA with antigen prepared by recombinant gene technology, there is further need for reliable confirmatory tests.

In-vitro sensitivity of Bacteroidaceae, clostridia and propionibacteria to newer antimicrobial agents.

The susceptibility of 220 fresh clinical isolates of Bacteroidaceae, clostridia and propionibacteria to imipenem, ceftazidime, ciprofloxacin and four further substances were established by agar dilution tests. Imipenem was unique among the seven test antibiotics in that it was active against all the bacteria investigated. Whereas clindamycin suppressed all Gram-positive and 94 X 8% of the Gram-negative strains tested, and metronidazole was effective against all but the propionibacteria, ceftazidime and ciprofloxacin showed satisfactory activity against the Gram-positive bacteria only.