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Within a 13-year period (1970-1982) there were seen 18 cases of A-streptococcal septicaemia (age range 18-77 years), 1.3% of all septicaemia cases in this time. The portal of entry was most often a banal skin infection. Typically the disease occurred suddenly and took a fulminating course with the clinical picture of severe septicaemia. In more than half the patients septic complications occurred. Despite correct antibiotic treatment pyrexia disappeared only slowly. Four patients died of septic shock. In every case with an acute septic course and a suspicious cutaneous focus, one should think of A-streptococcal septicaemia and, if necessary, give penicillin in high dosage even before the bacterial culture result is known.

Microbiological investigations showed a positive culture in 430 out of 1540 venous catheters and shunts for dialysis. In 21 cases, a mixed culture with two different specific organisms was present. Of the total of 451 isolated organisms, 362 were gram-positive cocci and only 56 gram-negative bacillaceae. Staphylococcus epidermidis was by far the most frequent pathogen (n = 228), staphylococcus aureus in second place (n = 94). Among the gram-negative organisms, germs of the Klebsiella-Enterobacter group and Pseudomonas aeruginosa dominated. Staphylococcus aureus represented 31% of all germs isolated from Scribner shunts and Brescia fistulas. On the other hand the causative organism could be isolated in only 18% of the infected venous catheters. Staphylococcus aureus was the most frequent pathogen in septicemia due to catheters; in 16 out of 24 patients this microorganism was found in both cultures drawn from the blood and from the catheter. In 16 cases, a venous catheter led to septicemia, a shunt for chronical dialysis in 2 cases only. The frequency of infections caused by catheters can be significantly lowered by prudent care of the site of insertion, sterile handling and short indwelling time.

Toxoplasmosis encephalitis developed in three male homosexuals with AIDS. Clinical symptoms of encephalitis began with a nonspecific organic mental syndrome. In two cases there developed late focal symptoms. There were light to moderately severe generalized EEG changes with additional focal signs. CSF findings and toxoplasmosis titres were not diagnostically altered. Computed tomography demonstrated multiple areas of decreased density in cortex and cerebellum. Administration of pyrimethamine and sulfamethoxydiazine to the three patients brought about clinical improvement within a few days and regression of abnormal CT changes within a few weeks of onset of treatment. One patient died after an encephalitis recurrence: autopsy demonstrated toxoplasma pseudocysts in immediate proximity to small necrotic foci in the brain. The possibility of toxoplasma encephalitis should be considered in AIDS patients who develop an organic mental syndrome. Often the diagnosis can only be made after response to a trial of toxoplasmosis treatment.

In den letzten Jahren wurden Daten veroffentlicht, die eine grundlegend neue Interpretation der Pathogenese der Arteriosklerose (Atherosklerose) erlauben. Hiernach ist die Arteriosklerose das Resultat einer ultrachronischen persistierenden Infektion der Gefase mit Chlamydia pneumoniae. Entsprechend ist die Arteriosklerose keine multifaktorielle Erkrankung durch unterschiedliche Risikofaktoren, sondern als chronische Chlamydienarteriitis bemerkenswert einfach erklart. Fur die Chlamydienthese bestehen starke Argumente wie die Korrelation zwischen koronarer Herzkrankheit u. a. arteriosklerotischen Manifestationen mit Antikorpern gegen Chlamydia pneumoniae, den Nachweis von Chlamydia pneumoniae in Atheromen, der Erzeugung einer protrahierten Arteriitis im Tierversuch und erfolgreiche Interventionsstudien mit Antibiotika bei Arteriosklerose. Interventionsstudien bei koronarer Herzkrankheit und anderen Manifestationen der Atherosklerose sollten in nachster Zeit folgen. Fernziel aber sind Praventionsstudien bei jungeren Erwachsenen ohne Arteriosklerosemanifestationen.

Das Problem der Resistenzentwicklung gegen Antibiotika ist so alt wie ihre Anwendung. Methicillinresistente Staphylococcus aureus (MRSA) sind neben ihrer Resistenz gegen Isoxazolylpenicilline auch zu einem sehr hohem Prozentsatz gegen andere staphylokokkenwirksame Antibiotika resistent. Glykopeptidresistente Enterokokken stellen ein weltweit im unterschiedlichen Umfang zunehmendes Problem dar, aber auch Staphylococcus aureus mit reduzierter Empfindlichkeit gegen Glykopeptide konnten in Zukunft ein therapeutisches Problem werden. Der vorliegende Beitrag beschreibt die Ursachen und Verbreitung der zunehmenden Resistenzentwicklung und gibt Empfehlungen fur aktuelle und zukunftige Therapieoptionen.

Dynamic mechanical and stress-optical measurements on nematic liquid single elastomers have been carried out both in the nematic and in the isotropic phase. In case of shear stress and in case of tensile stress applied parallel to the director the compliances were not affected by the nematic-isotropic transition. For tensile stress oriented perpendicular an increased compliance was observed in the vicinity of the phase transition. The stress-optical coefficients for tensile stresses applied pararallel and perpendicular to the director both increase on approaching the nematic-isotropic transition. In the isotropic phase its temperature dependence is well described by the Landau-de Gennes theory. Far from the transition temperature in the nematic phase other mechanisms superpose this behavior, leading to negative stress-optical coeffients for stress parallel, and positive coefficients perpendicular to the director.

Patterns formed by inversion walls in nematic layers exposed to a rotating magnetic field were studied. Dilute solutions of a mesogenic side group polymethacrylate in a low molecular weight liquid crystal (5CB) were used in comparison with the pure solvent. As found in a previous work, in this system the intensity of backflow (fluid flow induced by director rotation) can be controlled by the polymer concentration due to a specific increase of shear viscosity coefficients. In the synchronous regime of director rotation no significant effects of backflow on the dynamics of the walls are observed. Dynamic solitons known from the synchronous regime were also found at asynchronous rotation, when soliton lattices are formed by continuous nucleation. Here comparison with theory for given values of the lattice period shows soliton currents significantly reduced by backflow. Two of the three additional pattern forming states exclusively found at asynchronous rotation were completely suppressed in solutions with sufficient polymer concentration. The third of these states is affected by backflow in the growth rate of its patterns. Numerical calculations were performed to explain behavior of the patterns in the asynchronous state. For pure 5CB a quantitative comparison with the experiment was possible.

Zusammenfassung. Im Rahmen einer Pilotstudie sowie einer deutschen multizentrischen Studie wurden 40 AIDS-Patienten mit Fluconazol-resistenter oropharyngealer Candida-Infektion mit Itraconazol-Suspension (200–800 mg/Tag) oral behandelt. Bei 39/40 Patienten konnte initial eine Heilung oder deutliche Besserung erzielt werden. Im Gegensatz zum guten klinischen Behandlungsergebnis fanden sich jedoch nur bei 6 Patienten eine komplette Keimelimination in den Mundspulwasserproben, bei 29 Patienten kulturell eine Keimzahlreduktion - allerdings nicht unter 102KBE/ml (koloniebildende Einheiten pro ml) - und bei 4 Patienten unverandert hohe Keimzahlen. Als Haupterreger wurde C. albicans isoliert. Auch bei Langzeitanwendung war die Itraconazol-Suspension gut vertraglich; nur bei 2 Patienten muste die Therapie wegen Transaminasenanstieg vorzeitig abgebrochen werden. Es fanden sich erhebliche individuelle Schwankungen der Itraconazol- bzw. Hydroxy-Itraconazol-Serumkonzentrationen, die nur in geringem Ausmas mit den klinischen und mykologischen Behandlungsergebnissen korrelierten. Die orale Applikation von Itraconazol in flussiger Form fuhrt durch die gleichzeitige lokale und systemische Wirksamkeit (duales Therapiekonzept) zu einer Wirkungssteigerung. Itraconazol-Suspension ist bei Fluconazol-Versagen eine wertvolle Alternative zur nebenwirkungsreichen Therapie mit Amphotericin B. Summary. Forty AIDS patients suffering from fluconazole-resistant oropharyngeal candidosis were treated with oral itraconazole solution (200–800 mg/day). In 39/49 patients the disease could be initially cured or significantly improved. In contrast to the good clinical results, however, only in six patients a yeast count reduction was observed, and in four patients unchanged high yeast counts persisted. The main pathogen was C. albicans. Even in longtime treatment itraconazole solution was well tolerated. In two patients only the therapy had to be stopped due to the increase of transaminases. Considerable individual deviations in serum concentrations of itraconazole or hydroxy-itraconazole, respectively, were observed which correlated only to a minor degree with clinical and mycological results. Application of itraconazole in a soluble preparation caused an increase in efficacy due to simultaneous local and systemic action. In the case of resistance to fluconazole the itraconazole solution is a valuable alternative to the administration of amphotericin B which is rich in adverse reactions.

A combination of director reorientation experiments with dielectric relaxation spectroscopy was used to study the relation between the rotational viscosity γ1 and the rotational diffusion constants in nematic compounds with different association tendency. Increased values for γ1 were found for compounds showing strong association. This is explained by increased rotational friction of the associates due to the necessary translational motion of the molecules within these groups. For nonassociating compounds, γ1 was found to be described quantitatively by Marrucci’s theory, when, in addition, the tube dilation effect described by Doi for the rotational diffusion in an orientationally ordered environment is taken into account.

The broadspectrum quinolone antibiotics ciprofloxacin and ofloxacin were tested for activity against the atypical mycobacterium M.fortuitum. In vitro minimal inhibitory concentrations (MIC) were done in Brain Heart Infusion broth and intracellular determinations in Medium 199 cell culture medium. The PMNs with intracellular bacteria and controls with or without drugs were incubated for six hours at 37°C. Hourly, 0.1 ml aliquotes were taken for colony forming units (cfu) assays. In vitro and intracellular MIC's for ciprofloxacin were 0.125mg/l and 0.625 mg/l respectively, while for ofloxacin they were 0.2mg/l and 0.4 mg/l, respectively.

Periodic pattern formation at the Frederiks transition in the magnetic field has been studied for dilute solutions of a polymethacrylate with mesogenic side groups in a nematic solvent, pentylcyanobiphenyl (5CB). For this purpose, a combination of dielectric measurements and direct pattern observations was used to determine the twist elastic constant K 2 , the rotational viscosity γ 1 , and the wavelength of the periodic distortion λ. For polymer concentrations 0 ≤ w ≤ 1 % the values of λ were found to follow a power law λ (B − B c ) −β with β 1/2, where B c is the critical field for formation of periodic patterns. A strong effect of the polymer molecules on B c has been observed, due to the contribution of the macromolecules to the shear Miesowicz viscosity coefficient η a being large compared to the effect on γ 1 . In a simple phenomenological model, which is constructed analogous to the Landau theory for second order phase transitions, and uses an expansion of the growth rate of the patterns in powers of the wavenumber k = 2π/λ, we describe correctly the observed power law

In this prospective multicenter trial, treatment strategies for 1573 patients with neutropenia

A combination of dielectric relaxation spectroscopy and measurements of the rotational viscosity by director reorientation experiments was used to study nematic side-group polymethacrylates with different molecular weight. The contribution γ of the mesogenic groups to the total rotational viscosity γ is estimated on the base of Marrucci's theory from the rotational diffusion constant Dr obtained by relaxation frequency determinations. γ then is used to separate the contribution Δγ1 of the friction due to rearrangements of anisotropic ordered polymer backbones to γ. The molecular weight dependence of Δγ1 can be described by a power law, as predicted by Brochard's theory. The resulting exponent gives evidence for the presence of nonentangled random coil conformations.

The relation between the rotational viscosity γ1 of binary nematic mixtures and the different rotational diffusion constants Dri of their components was studied by a combination of director reorientation experiments with dielectric relaxation spectroscopy. Marrucci’s theory for the viscosity of single component nematics can be applied when the weighted reciprocal rotational diffusion constants are averaged arithmetically. An explanation is given by considering the sum of the molecular frictional torques.

Dynamic stress-optical measurements on liquid crystalline elastomers with different crosslinking densities have been carried out in the isotropic phase. The appearance of two relaxation processes in the spectra is probably due to the side-on attachment of the spacers to the mesogenic groups. The relaxation frequencies and the relaxation strength of the processes show critical behavior in qualitative agreement with the Landau-de Gennes theory. The strong cross-linking density dependence of the relaxation strengths provides evidence that the cross-linking points locally perturb the liquid crystalline order

The ability of human monocytes to phagocytize and respond to infection by Mycobacterium fortuitum was tested using the method of Crowle and May. The monocytes were obtained from heparinized donor blood samples and separated from lymphocytes by adherence to plastic surfaces. M. fortuitum infection was performed immediately. Intracellular viability was indicated by colony forming units (CFU) done at 2 hour intervals. Monocytes were found to cause a rapid reduction in CFU during the first 2 hours of incubation. The rate of killing of M. fortuitum decreased thereafter but continued for the entire 8-hour study period. In parallel tests, ciprofloxacin and ofloxacin were added to the culture medium. Increased intracellular killing was observed with drug concentrations above 2 x MIC in both cases. Ofloxacin showed better antimycobacterial effects than ciprofloxacin.

Nematic, side-group polymethacrylates [CH 2 C(Me)(COO[CH 2 ] 6 OPHCOOPhR)] n (R= CN, OMe) with different molecular weightg were studied by a combination of dielectric relaxation spectroscopy and measurements of the rotational viscosity by director reorientation experiments. The rotational diffusion constant obtained by relaxation frequency determinations allows the estimation of the contribution γ 1 m of the mesogenic groups to the total rotational viscosity γ 1 t on the basis of Marrucci's theory. γ 1 m then is used to separate the contribution Δγ 1 of the friction due to rearrangements of anisotropic ordered polymer backbones to γ 1 t .? The molecular weight dependence of Δγ 1 can be described by a power law, as predicted by Brochard's theory

Structures of semi crystalline high-molecular weight polyethylene and their changes with temperature were studied by analysis of Raman spectra. Decomposition of spectra into contributions of an orthorhombic crystalline phase, a meltlike phase, and two kinds of transition regions yields the respective mass fractions. The results of temperature dependent measurements is indicative of a largely reversible surface melting process, the transition regions being located at the crystal surfaces. As-polymerized samples show a large fraction of the intermediate phase. Annealing leads to a reduction of this phase. © 1993 John Wiley & Sons, Inc.

Pretransitional order at the free surface of the isotropic phases of two phenylcyclohexances (PCH5 and PCH7) was studied by reflection ellipsometry under variation of the angle of incidence. Data analysis shows a logarithmic divergence of the boundary layer thickness when the temperature approaches the isotropic‐nematic transition point, indicating complete wetting behavior. The data are well represented by fits to a model based on a Landau–de Gennes approach, yielding order parameter profiles of the layer.

In a randomized, open study, the efficacy of fluconazole as a prophylaxis of recurrent oral candidiasis in patients with advanced stages of HIV-infection (CD4 cell count less than 100/mm3) was studied. For this purpose, the frequency of episodes of oral candidiasis during two different prophylaxis regimens (50 mg/day vs. 100 mg/day) were compared to an untreated control group. Sixty-five HIV-positive patients were included in the study from May, 1989 to January, 1990. Of these, 58 were evaluated over an observation time of 137-215 days. Prophylaxis with fluconazole clearly reduced the occurrence of oral candidiasis. In 20 out of 21 patients in the untreated control group, a total of 60 relapses occurred. In the prophylaxis group receiving 50 mg/day (group 2), two out of 18 patients had four relapses. In the group receiving 100 mg/day (group 3), four out of 19 patients had nine relapses in total. Of 3575 observation days in the control group, treatment due to oral candidiasis was necessary on 393 days (28%). In group 2, on 57 of 3316 days (2%), fluconazole in a higher dosage was administered for treatment. In group 3, relapse treatment with fluconazole 200 mg/day, or treatment with ketoconazole, became necessary in 116 out of 3314 observation days (3%). In all relapses, Candida albicans cfu greater than 10(3)/ml were isolated in the oral wash-outs. As compared to the untreated control group, fluconazole prophylaxis in a daily dosage of 50 as well as 100 mg led to significantly less frequent relapses of oral candidiasis (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

106 HIV-positive patients with 129 episodes of oropharyngeal Candida infection were treated with fluconazole (50-300 mg/d). Treatment lasted from 4 to 23 days. The majority of patients were in more advanced stages of HIV infection (82% AIDS cases). Therapy with fluconazole led to complete healing or improvement of clinical symptoms in 93% of all treatment courses. However, according to cultural findings, an elimination or recession of pathogens was achieved in only 70% of cases. Cultural monitoring showed a slow reduction of pathogens, as opposed to a fairly rapid clinical improvement. Candida albicans was the most frequently isolated Candida species (n = 128); the most selected Candida species during treatment were C. glabrata, C. krusei, and C. inconspicua. It is remarkable that C. glabrata, a low-grade pathogen, caused enanthema in 2 patients and a typical oral thrush in 1 patient. Fluconazole was well-tolerated, and apart from mild gastro-intestinal symptoms in 1 patient, no severe side effects were observed.

La variation avec la temperature de la frequence F de la relaxation dielectrique Delta et de la viscosite rotationnelle γ de melanges du polysiloxane (−Si(Me)(R)O−) n (R=(CH 2 ) 4 -OPh-CO 2 -Ph-OMe) avec un nematogene est determinee surtout par la variation du coefficient de diffusion rotationnelle qui est decrite par la formule de Vogel-Fulder. L'effet du potentiel nematique sur F et γ est decrit par les theories de Martin-Meier-Saupe et Hess

To investigate whether the use of highly active antiretroviral therapy (HAART) is associated with an increased incidence of myocardial infarctions (MI) in HIV infected patients.Retrospective analysis of a cohort of 4993 HIV infected patients treated at our hospital between January, 1 1983 and December, 31 1998. The incidence of myocardial infarctions during 4 observation periods with different antiretroviral treatment strategies are compared. Possible risk factors for MI are evaluated by univariate analysis and using a multiple regression model.29 patients with MI were diagnosed between 1983 and 1998. The incidence of MI per 1000 patient-years increased from 0.86 (1983-86), 1.14 (1987-90), 0.59 (1991-94) to 3.41 (1995-98) respectively (p = 0.002). Age40, previous HAART therapy, homo-, or bisexual mode of HIV transmission and previous AIDS diagnosis were significantly associated with MI in univariate analysis. Age40 and previous HAART therapy remained significantly associated with MI in a multiple regression model.The incidence of MI in HIV infected patients increased in our cohort after the introduction of HAART.

Der koronar-arterielle Bypass (CABG: „coronary artery bypass graft surgery“) ist ein etabliertes chirurgisches Therapieverfahren der koronaren Herzkrankheit (KHK). Dabei wird meist die autologe V. saphena magna oder die A. mammillaria interna verwendet. Die wichtigste Komplikation der Bypasschirurgie ist die Gefasokklusion des Transplantats. Die Ursache des allmahlichen Bypassverschlusses ist eine rasant akzelerierende Arteriosklerose unter den veranderten Druckverhaltnissen.

The higher incidence of coronary infarction in younger males (age 35 to 60) is well known but difficult to explain.

Recent investigations allow a controversial but convincing interpretation of the pathogenesis of atherosclerosis (arteriosclerosis). Atherosclerosis can be apparently the result of ultrachronic persistent infection by Chlamydia pneumoniae and not the result of heterogenous risk factors. The main arguments for the chlamydial genesis are: Correlation of coronary heart disease and other atherosclerotic diseases and antibodies against Chlamydia pneumoniae. Chlamydia pneumoniae could be detected with different techniques (PCR, ICC, immunohistology, electromicroscopy, culture) in a high percentage in atheromas from different sites. Three successful international studies with macrolides in coronary heart disease. Target cells of atherosclerosis (endothelia, macrophages, muscle cells) can be infected by Chlamydia pneumoniae in vitro. Provocation of an arteriitis in animal experiments. The reduction of incidence of atherosclerotic diseases since the 1960s, probably due to advanced antibiotic therapy. Elevated acute-phase proteins and other inflammatory signs (CRP, WBC count, fibrinogen) briefly before occurrence of myocardial infarction. There are good arguments for intervention studies in coronary heart disease and other manifestations of atherosclerosis. The relevant antibiotics are licensed for chlamydial infections, cheap and safe. Meticulous records and long-term observation of patients need to be developed, sometimes contrary to interests of the pharmaceutical industry.

Die antiretrovirale Behandlung der HIV-Infektion wird mit Medikamenten durchgefuhrt, die die virusspezifischen Enzyme der Reversen Transkriptase oder Protease hemmen und dadurch den viralen Replikationszyklus unterbrechen. Das mogliche Versagen der antiretroviralen Medikamente beruht auf einer ungenugenden Hemmung der Virusreplikation. Grunde fur ein Therapieversagen konnen patientenbezogen oder virusbedingt sein. Liegen patientenassoziierte Faktoren wie z.B. Adharenz-Probleme vor, so kann unter Umstanden durch gezielte Aufklarung oder Therapievereinfachung Abhilfe geschaffen werden. Auch bei optimalen Therapiestrategien kann es allerdings ein Versagen der Therapie geben, z.B. bei gestorten Stoffwechselablaufen. In Einzelfallen verlauft beispielsweise die intrazellulare Phosphorylierung zu aktiven Metaboliten der Medikamente nur suboptimal.

The objective of this presented prospective randomized study was to compare the efficacy of empirical antimicrobial monotherapy with imipenem 3 x 0.5 g per day to 3 x 1.0 g per day for treatment of infections in neutropenic patients. A total of 192/220 febrile episodes were evaluable for clinical efficacy. The overall response rate was 53/93 (57%) vs. 57/99 (58%). Of the different infection types, fever of unknown origin (FUO) showed the best response, with defervescence in 29/41 (71%) and 36/42 (86%) cases, respectively (not significant). Unfavourable results were found in pneumonias [5/20 (25%) vs. 4/23 (17%)]. The median time until persistent defervescence was equal in both groups (2 days), likewise the median duration of imipenem therapy in responders (7 days). The most frequent micro-organisms were Gram-negative, documented in 22% of the febrile episodes in the lower dosage group vs. 17% of all episodes in the patients with imipenem 3.0 g per day (Gram-positives 17% vs. 14%, fungal 5% vs. 8%). In the lower dosage group, fever with abdominal symptoms occurred less frequently (8% vs. 15%), and significantly more patients tolerated imipenem without any side-effects (95.8% vs. 79.4%), especially regarding severe nausea/vomiting (2.1% vs. 11.8%). Of the initial non-responders, 35/40 (88%) vs. 41/42 (98%) were cured after therapy modification. There was no significant difference in the use of further antibiotics such as aminoglycosides, glycopeptides, ceftazidime or amphotericin B, except a marginally higher use of metronidazole in patients with imipenem 3.0 g per day (3% vs. 10%). Overall, we found no significant differences in efficacy between the two study groups, but more frequent side-effects with imipenem 3.0 g per day.

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.

The objective of the presented prospective, randomized study was to compare the efficacy of empirical antimicrobial monotherapy with piperacillin/tazobactam (PIP/TAZ) to cefepime (CEFP) for treatment of infections in neutropenic patients. From a total of 102 febrile episodes 100 were evaluable. The most frequent microorganisms were gram-negative, documented in 22% vs. 24% of the febrile episodes (gram-positives 18% vs. 16%, fungi 2% vs. 4%). The response rate was similar with 22/51 (43%) of episodes treated with PIP/TAZ vs. 19/49 (39%) with CEFP. Of the different infection types classified at the end of the febrile episodes, patients with fever of unknown origin (FUO) and primary bacteremias showed the best initial responses with 25/44 (57%) and 11/22 (50%). Lower initial response rates were found in pneumonias with totally 3/13 (23%) and other clinically documented infections with 2/21 (10%), without any difference between both groups. Gram positive infections showed a higher response with PIP/TAZ than with CEFP (4/9 vs. 0/8), gram negative responded less frequently (3/11 vs. 7/13). The median time until persistent defervescence was equal in both groups (2.5 vs. 2 days), likewise the response rates after the different steps of therapy modifications (change to imipenem or ceftazidim, or addition of gentamycin, vancomycin or amphotericin B). Totally, 96% of febrile episodes responded in both therapy arms. Overall, we found no significant differences in efficacy between the two therapeutic regimens. In conclusion, PIP/TAZ as well as CEFP might be a sufficient initial therapy for febrile neutropenia, but further randomized trials with larger patient numbers are necessary.

In the last years several new data allow a controversial but convincing interpretation of the pathogenesis of atherosclerosis (arteriosclerosis). Atherosclerosis can be apparently the result of ultrachronic persistent infection by Chlamydia pneumoniae and not the result of different risk factors. The main arguments for the chlamydial genesis are: 1. Correlation of coronary heart disease and other atherosclerotic disease with antibodies against C. pneumoniae. 2. C. pneumoniae could be detected with different techniques (PCR, immunohistology, electromicroscopy, culture) in a high percentage in atheromas from different sites. 3. Three international studies with macrolides in coronary heart disease were successful. 4. The target cells of atherosclerosis (endothelia, macrophages, muscle cells) can be infected by C. pneumoniae in vitro. 5. Positive animal experiments. The Koch-Henle criteria for the proof of the etiology are largely fulfilled--even if there are doubts about the validity of these criteria in chronic local infections. A number of unexplainable aspect of atherosclerosis can be seen in a new light. The higher incidence of coronary heart disease in young males has a parallel in the remarkable androtropism of many bacterial diseases (pneumococcal pneumonia, tuberculosis). The reduction of incidence of atherosclerotic diseases since 1965 can be explained by the much higher intake of doxycyclin and macrolides. The low incidence of coronary heart disease in France--sometimes regarded as an effect of red wine--can be explained as a result of a much higher use of antichlamydial antibiotics. The increase of inflammatory parameters (C-reactive protein, fibrinogen, leucocytes) before acute coronary infarction are not risk factors but signs of an active chronic infection. The interpretation is possible, that atherogenic changes in lipids like increase of LDL and decrease of HDL are not risk factors but consequence of chronic arterial infection by chlamydia. The low incidence of atherosclerosis in the tropics--despite high frequency of chlamydial infection--is difficult to explain. Vascular infection can be related with the age of the patient at the primary infection. With low hygiene, intestinal primary infections in early childhood can be possible. Arterial infection would be thus a result of a primary infection in adolescence ("yet another poliomyelitis story"). There are good arguments for the thesis that C. pneumoniae is the primary cause of atherosclerosis and not a secondary invader. The consequence, nevertheless, is similar: Antibiotics get a key role. The macrolides roxithromycin, azithromycin, clarithromycin and the tetracyclin doxycyclin fulfill the criteria as potential antichlamydial agents. In general a longer treatment (6 to 8 to 12 weeks) seems advisable. It is necessary to start international studies with antibiotics in coronary infarction and other clinical manifestations of atherosclerosis. The relevant antibiotics licensed for chlamydial infections are cheap and safe. Despite of the urgent need for controlled studies, it seems already justified to treat high-risk patients with antibiotics. Meticulous protocols and long-term control of patients are necessary to evaluate the therapeutic effects. Preventive studies in patients without clinical manifestation of atherosclerosis are urgently needed. The risks of resistance or side effects are neglectable, but the organisation of such studies would be very difficult.

Different treatment strategies for 1573 patients with neutropenia < 1000/µl and fever 38.5°C after cytotoxic chemotherapy were compared. 79% of patients had acute leukemia, 11.5% high-grade non-Hodgkin’s lymphoma, and 9.5% blast crisis of chronic myeloid leukemia or advanced myelodysplastic syndrome. Patients with unexplained fever were randomized to a three-phase sequential study for different established drug regimens. If an infection could be defined microbiologically or clinically, treatment modifications were determined.

Forty AIDS patients suffering from fluconazole-resistant oropharyngeal candidosis were treated with oral itraconazole solution (200-800 mg/day). In 39/49 patients the disease could be initially cured or significantly improved. In contrast to the good clinical results, however, only in six patients a yeast count reduction was observed, and in four patients unchanged high yeast counts persisted. The main pathogen was C. albicans. Even in longtime treatment itraconazole solution was well tolerated. In two patients only the therapy had to be stopped due to the increase of transaminases. Considerable individual deviations in serum concentrations of itraconazole or hydroxy-itraconazole, respectively, were observed which correlated only to a minor degree with clinical and mycological results. Application of itraconazole in a soluble preparation caused an increase in efficacy due to simultaneous local and systemic action. In the case of resistance to fluconazole the itraconazole solution is a valuable alternative to the administration of amphotericin B which is rich in adverse reactions.

L-697,661 is a human immunodeficiency virus type 1 (HIV-1)-specific nonnucleoside reverse transcriptase (RT) inhibitor. Its tolerability and activity in combination with zidovudine were evaluated in a 48-week double-blind study. One hundred nineteen zidovudine-naive HIV-1-infected patients with CD4 cell counts of 200-500/mm 3 received either combination therapy, L-697,661 alone, or zidovudine alone. Activity was assessed by CD4 cell count changes. Selection for L-697,661-resistant virus was monitored by susceptibility testing of RT expressed by circulating viral RNA. Therapy was generally well tolerated. All groups receiving zidovudine exhibited transient increases in CD4 cell counts, while the L-697,661 monotherapy group showed a significant decline and yielded RT >100-fold resistant to L-697,661 and associated with substitutions at RT residue 181. The RT from patients receiving combination therapy was maximally 15-fold less susceptible to L-697,661. Hence, cotreatment with zidovudine prevents selection of HIV-1 variants that are highly resistant to L-697,661 in patients naive to both compounds