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Background PKARIα (protein kinase A type I‐α regulatory subunit) is redox‐active independent of its physiologic agonist cAMP. However, it is unknown whether this alternative mechanism of PKARIα activation may be of relevance to cardiac excitation–contraction coupling. Methods and Results We used a redox‐dead transgenic mouse model with homozygous knock‐in replacement of redox‐sensitive cysteine 17 with serine within the regulatory subunits of PKARIα (KI). Reactive oxygen species were acutely evoked by exposure of isolated cardiac myocytes to AngII (angiotensin II, 1 µmol/L). The long‐term relevance of oxidized PKARIα was investigated in KI mice and their wild‐type (WT) littermates following transverse aortic constriction (TAC). AngII increased reactive oxygen species in both groups but with RIα dimer formation in WT only. AngII induced translocation of PKARI to the cell membrane and resulted in protein kinase A–dependent stimulation of I Ca (L‐type Ca current) in WT with no effect in KI myocytes. Consequently, Ca transients were reduced in KI myocytes as compared with WT cells following acute AngII exposure. Transverse aortic constriction–related reactive oxygen species formation resulted in RIα oxidation in WT but not in KI mice. Within 6 weeks after TAC, KI mice showed an enhanced deterioration of contractile function and impaired survival compared with WT. In accordance, compared with WT, ventricular myocytes from failing KI mice displayed significantly reduced Ca transient amplitudes and lack of I Ca stimulation. Conversely, direct pharmacological stimulation of I Ca using Bay K8644 rescued Ca transients in AngII‐treated KI myocytes and contractile function in failing KI mice in vivo. Conclusions Oxidative activation of PKARIα with subsequent stimulation of I Ca preserves cardiac function in the setting of acute and chronic oxidative stress.

HIV patients are overexposed to hospital environment, immune suppression, and antibiotic prophylaxes. Therefore, with HIV positive patients an increased risk for resistant bacterial rods is to be expected. The purpose of this case-control study was to determine the susceptibility patterns of pneumococci from adult patients in relation to their HIV status and to compare both patient groups.Between January 2001 and December 2005, samples from internal medicine patients of one university hospital laboratory were investigated on culture of Streptococcus pneumoniae and in case of a positive vial, a resistance test was done by agar diffusion method. All patients with culture-confirmed infection due to pneumococci underwent a standardized retrospective evaluation in regard to demographic and clinical characteristics including HIV status.A total amount of 135 Streptococcus pneumoniae cultures could be assigned to 64 HIV-positive (A) and 71 HIV-negative patients (B), with susceptibility results for 134 isolates. Full susceptibility was seen in 44 (69.8% [A]) versus 42 (59.2% [B]) samples, reduced susceptibility ("intermediate-susceptible") was found in eight (12.7% [A]) versus 17 (23.9% [B]). Eleven (17.5% [A]) and twelve (16.9% [B]), respectively, out of all pneumococci were tested resistant to at least one antibiotic. Among these, resistance to erythromycin was most relevant (11.1% [A] and 11.3% [B]). None of the tested rods was resistant to penicillin. All differences between groups for susceptibility testing were not found significant. HIV-negative patients were significantly older, needed more often hospitalization and intensive care, and cultures for pneumococci were more frequently positive in primary sterile materials, such as cerebrospinal fluid and blood. The difference concerning death within 28 days following positive sample was just not significant as well as in immune suppression status of patients. HIV patients experienced more frequently an infection relapse and were more frequently smokers.No obvious difference in pneumococci resistance patterns was observed between HIV-positive and HIV-negative adult patients. The absence of resistance to penicillin underscores the importance of beta-lactams in case of typical community-acquired pneumonia; therefore, this class of antibiotics should be included in treatment guidelines as first-line drugs also for HIV patients. HIV-negative controls of this study were more aged and suffered from a higher morbidity, however, the fact that they were not significantly less immune suppressed may be special character of a university hospital control patient group. HIV patients presented in an earlier stage of their pneumococcal disease, probably due to a direct access to tertiary hospital medical supply. A higher relapse rate underscores the importance of pneumococcal vaccination for HIV patients.

Dt. Version erschienen u.d.T.: Streptokokkeninfektionen der Haut und Schleimhäute ([https://doi.org/10.1111/j.1610-0387.2007.06287_supp.x](https://doi.org/10.1111/j.1610-0387.2007.06287_supp.x))

Microbe-induced (infectious) endocarditis is an endovascular infection, caused mainly by bacteria, of cardiovascular structures. The major predilection site are the native heart valves, but involvement of implanted intracardiac foreign material is increasingly being seen. The mortality rate of infectious endocarditis depends on clinical factors and the causal agent, but also on the time of the establishment of the diagnosis and the initiation of appropriate treatment. In Germany, the current mortality rate ranges up to 18%. Between January 2003 and July 2004, with the aim of improving patient care and thus the outcome of this condition, a guideline commission worked out recommendations for the diagnosis, treatment and management of the disease for the use of general practitioners and hospital physicians, in particular microbiologists, infectiologists, cardiologists and cardiac surgeons. The basis for this guideline was the systematic search through the literature of the European guideline. On the 16th and 28th of June 2004, the entire guideline was formerly approved in a nominal group process.

Intensified chemotherapy-induced long-term neutropenia is the main cause for morbidity and mortality of patients with hematologic malignancies. The successful management of neutropenia is based on hygienic procedures antimicrobial prophylaxis and therapy, and diagnostics. Until today, Co-Trimoxazole or fluoroquinolenes and oral amphotericine B are the prophylactic standard. The initial therapy of febrile neutropenia has to be started empirically before identification of causative pathogens or infectious foci. The febrile episodes should be treated with broad spectrum antibiotics (combinations or monotherapy) due to the spectrum of microorganisms or resistance situation at hospital. In case of non-response after 3-4 days the initial therapy should be modified, in addition to further antibacterial therapy the start with an antifungal drug has to be recommended. In patients with pulmonary infiltrates the early treatment with amphotericine B has been shown to be more advantageous than delayed antifungal therapy. Furthermore, the antibiotic therapy is based on proven microorganisms, susceptibility testing and infectious foci. The value of interventional treatment with G-CSF or GM-CSF is controversely discussed. An uncompromising handling of febrile neutropenia is necessary to reduce the mortality due to infections in patients with hematologic malignancies.

A fourteen-year-old girl with acute otitis media died from gram positive sepsis and toxic shock despite intensive treatment. The definitive bacteriological results showed positive cultures for both S. aureus and S. pyogenes serotype A. In vitro the bacteria produced the bacterial superantigens TSST-1, enterotoxin A, enterotoxin C (S. aureus) and erythrogenic toxin C (S. pyogenes). The patient presented with large flaccid sterile bullae on her chest and arms as well as necrotizing fasciitis. Tzanck test showed keratinozytes without necrosis and no inflammatory cells. Frozen-section and conventional skin biopsy specimens revealed subcorneal intraepidermal cleavage. These cytological and histological findings are those of staphylococcal scalded skin syndrome (SSSS) and differ from bullous erysipelas or toxic epidermal necrolysis (TEN). Therefore bacterial exotoxins are most likely responsible for the intraepidermal blistering in our case just as in SSSS. Bullae are an unfavorable prognostic sign in gram positive toxic shock syndrome. Both Tzanck test and frozen-section biopsy are easy to perform and useful in the early and rapid recognition of gram positive bullous toxic shock syndrome.

After eating a meal of poultry a 41-year-old man fell ill with severe diarrhoea, persistent high fever of around 39 degrees C, dehydration and somnolence. On admission to hospital physical examination was normal except for signs of dehydration. The blood count showed a leukocytosis (13,300/microliters) with 60% stab-form neutrophils. The erythrocyte sedimentation rate was raised to 49/82 mm. Also increased were the serum concentrations of creatinine (3.5 mg/dl), creatine kinase (179 U/l), lactate dehydrogenase (298 U/l) and C-reactive protein (16.8 mg/dl). Bacteriological and virological examinations of blood and stool were negative. A normal fluid and electrolyte balance was re-established. But as there was no improvement, ampicillin was administered, 2 g three times daily, then ciprofloxacin, 500 mg two times daily, and finally combined with metronidazole, 500 mg three times daily. Despite this treatment a chest radiograph on the tenth day revealed an infiltration in the left basal lung segment, and the legionella titre became positive at 1:2045. The antibiotic treatment was changed to 150 mg roxithromycin two times daily. The fever fell within 3 days and the diarrhoea stopped after 5 days. He was discharged free of symptoms after 24 days.

The bovine spongiform encephalopathy, a new bovine disease, was diagnosed first in the U.K. in 1985. Primarily an object of interest to scientific and news media, it has become a subject of research to some specialists only. Some aspects seem to point out the importance and potential danger of this disease to humans, too. Its similarity to other chronic degenerative forms of central nervous diseases is discussed.

Human epidermal Langerhans cells play an important role in the immunoregulation of the skin. We measured the numbers of CD(3+)-, CD(8+)-, CD1a(+)-, HLADR(+)-, IL2R(+)-, CD(4+)- and CD68 positive cells in the skin of 8 asymptomatic HIV-infected Persons, 3 Patients with AIDS and 11 healthy volunteers by suction blister technique. Our results indicate increased numbers of CD1a+ cells and increased numbers of CD4+ cells in the epidermis in asymptomatic HIV-infection. At the same time CD68+ cells are decreased already in an early stage of HIV-Infection. The number of CD1a/CD4+ cells is related to the degree of immunodeficiency. This fact might be caused by the activation of MPS.

The incidence of bacteremia after application of a dental irrigator was investigated in 100 healthy volunteers. Venous blood was inoculated in routine blood culture bottles one, three and five minutes after dental irrigation. In 39 volunteers a transient bacteremia was detected, mainly Strep. Viridans was cultured. Incidence correlated with the grade of oral hygiene und periodontal disease.

The in vitro activity of cefazolin, cefoxitin und amikacin alone and in combination was determined via membrane filtration against E. coli (n = 2), K. pneumoniae (n = 2) and of cefoxitin and amikacin against Proteus vulgaris (n = 1). Therapeutically achievable concentrations of cefazolin (10 micrograms/ml), cefoxitin (10 micrograms/ml) and amikacin (10 micrograms/ml) lead to a rapid bactericidal effect against all of our strains. The combination of cefazolin (10 micrograms/ml) and amikactin (5 micrograms/ml) and cefoxitin (10 micrograms/ml and amikacin (5 micrograms/ml) was synergistic against only one of the 2 K. pneumoniae strains. Cefoxitin and amikacin were antagonistic against the P. vulgaris strain but synergistic against both E. coli strains.

Imipenem/cilastatin was used for the treatment of 594 bacterial infections in 545 patients at a dosage of 1.5 g/day (n = 283), 2.0 g/day (n = 129), 3.0 g/day (n = 102), or 4 g/day (n = 11). The most common indications for therapy were nosocomial pneumonias followed by intraabdominal postoperative infections, and skin and soft tissue infections. Out of 1171 bacterial strains isolated from 932 patients, seven showed primary resistance to imipenem. The causative agent was eliminated in 87% of the patients. Treatment failed in 24 of the 594 patients. In 35 patients therapy was stopped because of side effects. The most frequent side effect was local irritation at the site of intravenous application.

Marked differences exist between antibacterial activity in human bile and broth. Whereas penicillins and cephalosporines exhibit virtually the same activity in broth and bile, tetracycline shows a great lose, and the activity of the aminoglykosides is increased in bile. Minimal inhibitory concentrations of chlorampenicol and co-trimoxazole are also different in broth and human bile. The differences in activity are related to the pH although not all deviations can be attributed to the effect of the pH. These results should be considered when treating gallbladder infections.

49 patients were given cefoxitin in combination with azlocillin, and 15 were given an aminoglycoside as well when severe bacterial infection was suspected. In 39 cases a prompt amelioration of the clinical signs of infection was observed. Of the 17 patients who died, a post-mortem was performed in seven; only in four were signs of bacterial infection present; one had tuberculosis and one had a cytomegalovirus infection. The combination therapy was well tolerated and side-effects were rare; no bleeding complications were seen. Clinical signs of possible antagonism between the two beta-lactam antibiotics were not observed.

In investigations into the dosis-activity relationships of bactericidal antibiotics used against E. coli, K. pneumoniae and Staph. aureus four types of activity could be demonstrated. The penicillin type shows almost no improvement in bactericidal activity despite increasing the dosage above a certain level. An increase in concentration of aminoglycoside antibiotics led to a more rapid killing of the bacteria. In cefalotin there was a linear dosis-activity relationship: rising concentrations of antibiotics led to an ever increasing bactericidal effect. The paradoxical bactericidal effect ("Eagle effect'') described for penicillin G with enterococci could not be demonstrated.

In an open clinical trial, out-patients with respiratory tract infections were given 200 mg ofloxacin b. i. d. orally. 36 had acute bronchitis and pneumonia was diagnosed in 44. The average duration of therapy was nine days for bronchitis and 12 days for pneumonia. In the sputum of bronchitis patients, Haemophilus influenzae (n = 25), Streptococcus pneumoniae (n = 18), Branhamella catarrhalis (n = 2) and Pasteurella multocida (n = 1) were isolated. 17 H. influenzae and 12 S. pneumoniae were eliminated. All 20 S. pneumoniae strains isolated from patients with pneumonia were eliminated. A cure or improvement of clinical symptoms was seen in 32 of 36 cases of bronchitis and in 33 of 44 cases of pneumonia treated with ofloxacin.

Seven patients were treated for bacterial infections with imipenem/cilastatin. Imipenem is a new broad-spectrum beta-lactam antibiotic with antimicrobial activity against gram-positive and gram-negative bacilli. Before and during treatment parameters of blood coagulation and platelet function were studied. Blood coagulation was not influenced by the antibiotic. But there was a temporary inhibition of collagen-induced platelet aggregation during the first days of treatment. No clinical signs of enhanced spontaneous bleeding tendency were observed.

Minimum inhibitory concentrations (MIC) for penicillin (PEN), ampicillin (AMP), cephalothin (CEF), cefazolin (CEZ), carbenicillin (CAR) and ticarcillin (TIC) were determined against Strep. faecalis, E. coli, K. pneumoniae, Prot. mirabilis and Ps. aeruginosa in Sensitivity Test Broth (STB) and human urine. Marked differences were seen in MIC between these two media, especially against P. mirabilis strains tested. Against E. coli the MIC of AMP, CEF and CEZ were similar or slightly lower in urine than in STB. MIC for CAR against E. coli were higher in urine. Against K. pneumoniae the MIC for CEF and CEZ were 2-4fold higher in urine than in STB. The activity of CAR and TIC against Ps. aeruginosa was lower in urine. Albeit high concentrations of antibiotics (up to 800fold) no inhibition was achieved in urine against P. mirabilis by AMP, CEF or CEZ. Only against Strep. faecalis all tested antibiotics had lower MIC in urine than in STB.

Azlocillin, in vitro four to eight times more effective against Pseudomonas aeruginosa than carbenicillin, was administered to 30 patients severely ill and having an additional pseudomonas infection. The drug was given at a dose of 4-6 g, in one case 8 g, per day, sometimes together with an aminoglycoside. Treatment was effective in 20, improvement occurred in five and failure only in four. In one instance the effect of the drug could not be evaluated. Results were particularly striking in septicaemia and necrotising external otitis. Pulmonary and wound infections in patients with circulatory disturbances did not respond so well. There were no serious side effects. The drug should not as yet be used at too high a dosage.