Candida keratitis and endopthalmitis after corneal transplantation; two case reports, a novel regimen and literature overview of therapeutic options.

PURPOSE: To evaluate treatment options for candida keratitis and endopthalmitis after corneal transplantation. METHODS: Case reports and literature review. RESULTS: Two patients with keratitis due to Candida glabrata/parapsilosis after corneal transplantation were successfully treated with a combination of topical voriconazole, intracameral voriconazole and amphotericin B, and systemic treatment with flucytosine. CONCLUSIONS: Natamycine and voriconazole topically are preferred therapeutic options for the treatment of fungal keratitis. Systemic flucytosine is a useful alternative additive, particularly for countries where natamycine is not registered as a pharmaceutical agent.

Renal transplant patient survives a donor-derived abdominal invasive mucormycosis (Lichtheimia ramos a).

Mucormycosis is a life-threatening invasive fungal infection, most commonly described in severely immunocompromised patients. It is characterized by rapid invasive growth of the fungus and often with fatal outcome. We report a case of a renal transplant recipient diagnosed with a donor-derived invasive mucormycosis. In this patient, we used a step-wise approach of withdrawal of immunosuppressants, antifungal induction therapy, extensive surgical debridement of all (potentially) infected tissue, abdominal irrigation of liposomal amphotericin B and interferon gamma. Due to rapid diagnosis and intensive therapy the patient survived.

High prevalence of azole resistance in Aspergillus fumigatus isolates from high-risk patients.

OBJECTIVES: Aspergillus fumigatus is the leading cause of invasive aspergillosis. Adequate treatment is complicated by an increase in azole resistance. Here, the incidence of voriconazole, posaconazole and itraconazole resistance in clinical isolates from high-risk patients from either the haematology ward or the ICU of the University Medical Center Utrecht in the period 2011-13 is analysed. Putative clonality of resistant strains was tested through cyp51A and microsatellite typing. METHODS: Primary A. fumigatus isolates from 105 patients were collected by an unbiased routine diagnostic-driven approach and phenotypically tested for azole susceptibility. Of the 105 isolates, 5 were from patients with a proven invasive A. fumigatus infection, 48 were from patients with a probable invasive A. fumigatus infection and 52 were from patients with non-invasive infections. Real-time PCR and cyp51A gene and strain typing were performed. RESULTS: Twenty-one out of 105 (20.0%) isolates were resistant to at least one of the three clinical azoles and 17/105 (16.2%) isolates were resistant (MIC >2 mg/L) to voriconazole, the empirical drug of choice for treatment of aspergillosis. There was a striking difference in the prevalence of triazole resistance, with 15.9% resistant isolates (25.0% in proven/probable patients) in the haematology population and 4.5% (10% in proven/probable) in the ICU. While the majority of isolates with elevated MICs of voriconazole were cyp51A related (17/23), both microsatellite and cyp51A sequence typing argue against clonal spread of resistant strains. CONCLUSIONS: This study reveals a high incidence of voriconazole resistance (16.2%) in A. fumigatus in high-risk patients. Our data stress the need for laboratory detection of azole resistance prior to treatment.

Myeloid related protein 8 and 14 secretion reflects phagocyte activation and correlates with disease activity in juvenile idiopathic arthritis treated with autologous stem cell transplantation.

OBJECTIVES: To determine whether myeloid related proteins (MRP8/MRP14), a complex of two S100 proteins related to neutrophil and monocyte activation, might be used as a marker for disease activity, and as an early indicator of relapse in juvenile idiopathic arthritis. PATIENTS AND METHODS: A group of 12 patients who underwent an autologous haematopoietic stem cell transplantation (ASCT) for refractory juvenile idiopathic arthritis (JIA) were studied. MRP8/MRP14 serum concentrations were determined by a sandwich enzyme linked immunosorbent assay (ELISA) as described. Improvement from baseline was described by a definition of improvement employing a core set of criteria as detailed previously by Giannini. RESULTS: After ASCT, MRP8/MRP14 serum concentrations in JIA showed a positive correlation with the Child Health Assessment Questionnaire (CHAQ; r=0.80) and erythrocyte sedimentation rate (r=0.45), but not with the total leucocyte count (r=0.26). Mean MRP8/MRP14 serum concentrations dropped markedly in the first three months after ASCT (p=0.0039) and clinical parameters of disease activity such as CHAQ markedly improved (p=0.0039). During a transient relapse there was an increase in MRP8/MRP14. CONCLUSIONS: MRP8/MRP14 serum concentration can be used as a marker for disease activity in patients who receive an ASCT for refractory JIA. This indicates a role of macrophage activation in the pathogenesis of JIA. The occurrence of MAS in three patients in this study was not preceded by significant changes in MRP8/MRP14 concentration.

Affinities of different proteins and peptides for lipopolysaccharide as determined by biosensor technology.

Biosensor technology was employed to study the specific interactions of different lipopolysaccharide (LPS)-binding proteins and peptides with LPS, using an LPS-coated surface. Two methods to immobilize biotinylated LPS to streptavidin-coated sensor chips (SA-chips) were evaluated. Biotinylated LPS in PBS or biotinylated LPS, pretreated with EDTA and sodium-desoxycholate, were injected across an SA-chip, resulting in a 'high-' and 'low- mass' LPS chip, respectively. While the 'high mass' LPS chip appeared to be unstable, the 'low mass' LPS chip resulted in reproducible binding curves for bactericidal/permeability-increasing protein (rBPI21) with a binding affinity corresponding to the literature (Kd: 3.75 nM). New Kd values were obtained for serum amyloid P component (SAP, Kd: 3.9 nM), a recently discovered new LPS-binding protein, and cationic protein 18 (CAP18, Kd: 0.58 nM). Moreover, binding affinities of bioactive BPI- and SAP-derived peptides could be determined. This study shows for the first time the applicability of biosensor technology to study interactions of proteins and peptides with LPS, using an LPS-coated sensor chip.

The potential for use of steam at atmospheric pressure to decontaminate or sterilize parenteral filling lines incorporating barrier isolation technology.

Barrier isolators that enclose aseptic filling equipment are being proposed as a means of: (1) assisting in achieving a 10(-6) sterility assurance level (SAL) in the filling area and (2) minimizing the clean environment required in the manufacturing area. The need for operator and maintenance access to the interior of the barrier isolators presents difficulties in achieving the above goals. Several methods are available for reducing the microbial level inside the isolation barrier. If the objective is the decontamination of all surfaces inside the enclosure, saturated steam at atmospheric pressure can be used. If the objective is to sterilize the inside of the enclosure, saturated steam at atmospheric pressure with added H2O2 can be used. Test data and practical interface considerations relative to various methodologies will be reviewed.

Systemic treatment of skin candidosis: a randomized comparison of terbinafine and ketoconazole.

Terbinafine is an antimycotic drug which has a much higher in vitro activity against dermatophytes than against yeasts. To investigate the clinical relevance of these in vitro data, 118 patients with cutaneous candidosis were enrolled in a randomized, double-blind study and allocated to a 4-week treatment with a daily dose of either 250 mg b.i.d. terbinafine or 200 mg once-daily ketoconazole. At the final assessment, 3 weeks after cessation of therapy, mycological cure rates (negative culture and negative microscopy) were 82% in the terbinafine group and 73% in the ketoconazole group. Effective treatment with negative mycology and no or minimal signs or symptoms could be achieved in 65% of those who received terbinafine and in 57% of those randomized to ketoconazole. Five per cent and 7% of the patients taking terbinafine and ketoconazole, respectively, complained about adverse events, which were usually mild and did not lead to discontinuation of treatment. In one patient in the ketoconazole group, abnormal liver enzymes were noted at the final laboratory assessment. The results of this study indicate that terbinafine 500 mg daily can be an alternative to ketoconazole when systemic treatment of skin candidosis is required.

Facilitated communication: the effects of facilitator knowledge and level of assistance on output.

Investigated facilitated communication with 10 adults with autism, and specifically examined the effects of facilitator influence and level of assistance as a function of facilitator knowledge of experimental stimuli. Six men and four women with autism served as subjects, ranging in age from 14 years to 51 years of age. Each subject had 6 experimental sessions, 2 with no help, 2 with partial assistance, and 2 with full assistance. Within each session, the facilitator had knowledge of the experimental stimuli in one half of the trials. Results revealed no cases of correct responding independent of facilitator knowledge of correct answers. Additionally, facilitator control was apparent in numerous cases in which typed output matched stimuli to which the facilitator, not the subject, had been exposed. Results suggest that clinical and educational use of the procedure should be curtailed pending further experimental investigation.

Polymorphism of the DQA1 promoter region (QAP) and DRB1, QAP, DQA1, DQB1 haplotypes in systemic lupus erythematosus. SLE Study Group members.

We have investigated the DNA polymorphism for the DQA1 promoter region (QAP) and HLA-class II DRB1, DQA1, and DQB1 genes in 178 central European patients with Systemic lupus erythematosus (SLE) using polymerase chain reaction and Dig-ddUTP labeled oligonucleotides. Increased frequencies of DRB1*02 and *03 are confirmed by DNA typing. In addition, the frequencies of DQA1*0501, *0102 and DQB1*0201, *0602 alleles are increased in the patients as compared to controls. The strongest association to SLE is found with DRB1*03 and DOB1*0201 alleles (p < 10(-7), p corr. < 10(-5) and p < 10(-6), p corr. < 10(-4), respectively). By investigating the DQA1 promoter region in the SLE patients we have detected nine different QAP variants. Increased frequencies of QAP1.2 and QAP4.1 are observed in patients as compared to controls (p < 0.05, p corr. = n.s.). Analysis of linkage disequilibria demonstrates a very strong association between QAP variants and DQA1, DRB1 alleles. Certain QAP variants are completely associated with DQA1 and DRB1 alleles, whereas others can combine with different DQA1 and DRB1 alleles. All DRB1*02-positive patients and controls carry QAP1.2, and all DRB1*03-positive patients and controls carry QAP4.1. Conversely, the QAP1.2 variant appears only in DRB1*02 haplotypes, while the QAP4.1 variant can be observed in DRB1*03, *11, and *1303 haplotypes. Based on the strong linkage disequilibria between DRB1-DQA1-DQB1 genes and between DRB1-QAP-DQA1, we have deduced the four-point haplotypes for DRB1-QAP-DQA1-DQB1 in patients and controls. Two haplotypes DRB1*02-QAP1.2-DQA1*0102-DQB1*0602 and DRB1*03-QAP4.1-DQA1*0501-DQB1*0201 are significantly increased in patients as compared to controls (p < 0.01, p corr. = n.s., RR = 1.8 and p < 10(-7), p corr. < 10(-5), RR = 3.1, respectively). The analysis of relative risks attributed to the various alleles of QAP, DQA1, and DQB1 as well as the investigation of the deduced DRB1-QAP-DQA1-DQB1 haplotypes leads to the conclusion that QAP4.1 and DQA1*0501 on the DR3 haplotypes are probably not involved in SLE susceptibility.(ABSTRACT TRUNCATED AT 400 WORDS)

[Effectiveness and mechanism of action of isoprenaline sulfate and clemastine hydrogen fumarate on histamine wheal-induced pruritus. A placebo-controlled proband study]. / Wirksamkeit und Wirkungsmechanismus von Isoprenalinsulfat und Clemastinhydrogenfumarat auf durch Histamin-Quaddelung ausgelösten Juckreiz. Eine Plazebo-kontrollierte Probandenstudie.

In order to investigate the effect of a gel containing isoprenaline and a gel containing clemastine hydrogen fumarate on histamine-induced skin reactions compared with placebo, a histamine solution was injected intradermally in four given fields on the backs of 12 healthy volunteers 15 min and 60 min after application of the gel preparations. The study was controlled by a non-treated field on the volunteers' backs. The main points of interest in this study included the size of the erythema reaction, the capillary blood flow and onset and intensity of itching. With respect to the size of the erythema reaction, both clemastine hydrogen fumarate and isoprenaline proved more effective than placebo in most cases. This superiority was, in some cases, statistically significant. There were no statistically significant differences between the gel preparations for the other parameters investigated. Clemastine hydrogen fumarate is regarded as a classical antihistamine, whereas a possible effect on the superficial circulation of the skin is being discussed for isoprenaline.

[Modification of skin sensitivity to selective UV-B (SUP) by water baths and various saline solutions--effect of various concentrations, duration of effect]. / Die Beeinflussung der Hautempfindlichkeit gegenüber selektiertem UV-B (SUP) durch Bäder in Wasser und verschiedenen Salzlösungen--Einfluss unterschiedlicher Konzentrationen, Dauer der Wirkung.

The skin sensitivity against selected UV-B (SUP) can be improved by baths in water or in salt solutions, leading to an average economizing of the radiation dose of about 50%. The best effect is achieved by a 0.3% salt bath (0.5 kg common salt per bath-tub). As the effect lasts for two hours, balneophototherapy may be carried out not only in hospitals but in practices, as well.

[Drug modification of mechanically evoked itching and the concomitant equivalents, erythema and wheals of the skin. Clinico-experimental studies]. / Zur medikamentösen Beeinflussung von mechanisch ausgelöstem Juckreiz und der begleitenden Aquivalente Erytheme und Quaddeln der Haut. Klinisch-experimentelle Untersuchungen.

In 20 volunteers with normal skin, itching and concomitant erythemas and wheals were produced by mechanical stimulation with a magnetic oscillation system. In a placebo-controlled, randomized double-blind study with twice cross-over, a calcium-vitamin-D-combination as single dose ampoules for peroral application was tested. A significant decrease (p less than 0,001) of the areas of erythema and wheal and itching in treated persons, compared with non-treated and placebo-treated volunteers serving for controls, is showing the antiallergic effectiveness of the tested preparation.

Effect of chlorpyrifos on Holstein steers and testosterone-treated Holstein bulls.

The effect of chlorpyrifos application was studied in a high-testosterone (testosterone-treated bulls) and a low-testosterone group (corn oil-treated steers). Frequent sampling of blood before and after 2 chlorpyrifos applications was used to monitor plasma testosterone concentrations and blood cholinesterase activities. Bulls had significantly higher testosterone concentrations (P less than 0.01) than did the steers, before and after the 1st and 2nd chlorpyrifos applications. Bulls had higher cholinesterase activities (P less than 0.01) than did steers before the 1st chlorpyrifos application. However, cholinesterase activity decreased more in bulls when compared with that in steers (P less than 0.01) after the 1st and 2nd chlorpyrifos application. Abnormal clinical signs were not observed in the steers, but 2 of 4 bulls had severe clinical signs of organophosphorus insecticide toxicosis after the 2nd application. Seemingly, chlorpyrifos is more toxic for testosterone-treated bulls than for corn oil-treated steers of similar age and weight.

The effects of an experimental prepaid group practice on medical care utilization and cost.

Rates of utilization and costs of medical care by a study group in a prepaid group practice, the Medical Care Group of Washington University (MCG), were compared prospectively over a three-year period with those of a demonstrably similar control group cared for by fee-for-service private physicians. MCG enrollees used twice the ambulatory services control enrollees did (p=less than 0.01), but used 23 per cent fewer hospital days (p=less than 0.01). Cost per diagnostic and therapeutic visit was similar for both groups; MCG preventive visits cost more. Increased numbers of MCG services provided led to increased ambulatory care costs for MCG over controls. Hospital utilization savings did not compensate for these increased costs. Thus prepayment in an organized setting did change hospital and ambulatory care utilization but did not reduce medical care costs. Other changes in medical care besides those which result from a different organization of medical care are discussed which might make control of medical care costs more likely.

Cost of medical care in an experimental study of prepaid group and fee for service practice.

Enrollees in an experimental prepaid group practice did use fewer hospital days and more ambulatory services than did control enrollees. In spite of this, however, savings generated from this reduction in hospital utilization were not enough to pay for the increased ambulatory services provided. Mechanisms for cost control must be sought in areas in addition to hospital savings. Two such areas are preventive services of unproved value, and physicians' services costs.