Infection control consequences – early Staphylococcal Scalded Skin Syndrome or Kawasaki Syndrome?

Childhood exanthemata are caused by a broad spectrum of common pathogens. Many exanthemata initially present very similarly, even though caused by different organisms, ranging from virus to bacteria and their respective toxins. In the majority of cases the diagnosis is only of academic value, since therapy does hardly differ. However, in some cases accurate and prompt diagnosis is paramount, since therapy and appropriate hygiene measures prevent morbidity and mortality. We present a case with two differential diagnoses, Staphylococcal Scalded Skin Syndrome and Kawasaki Syndrome, which demonstrates the importance of considering relatively rare conditions as the cause of a childhood exanthema and discuss differences in therapeutic and infection control management. From an infection control point of view, Staphylococcal Scalded Skin Syndrome is, in contrast to Kawasaki Syndrome, highly transmittable to other paediatric patients via the hands of the staff. Therefore maintaining correct hand hygiene as well as other infection control measures are of importance until the final diagnosis is established.     

Pomegranate juice may be a potential addition to anti-Behçet armamentarium: a hypothesis

Behçet’s disease (BD) is a systemic vasculitis. We speculate that local or systemic administration of the pomegranate juice may be useful in the treatment of BD. Immunomodulatory, antioxidants and antibacterial characteristics of pomegranate juice may rationalize this hypothesis.     

Resistance to an irreversible epidermal growth factor receptor (EGFR) inhibitor in EGFR-mutant lung cancer reveals novel treatment strategies

Patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer derive significant clinical benefit from treatment with the EGFR tyrosine kinase inhibitors gefitinib and erlotinib. Secondary EGFR mutations such as EGFR T790M commonly lead to resistance to these agents, limiting their long-term efficacy. Irreversible EGFR inhibitors such as CL-387,785 can overcome resistance and are in clinical development, yet acquired resistance against these agents is anticipated. We carried out a cell-based, in vitro random mutagenesis screen to identify EGFR mutations that confer resistance to CL-387,785 using T790M-mutant H1975 lung adenocarcinoma cells. Mutations at several residues occurred repeatedly leading to functional resistance to CL-387,785. These variants showed uninhibited cell growth, reduced apoptosis, and persistent EGFR activation in the presence of CL-387,785 as compared with parental H1975 cells, thus confirming their role in resistance. A screen of alternative agents showed that both an alternative EGFR inhibitor and a cyclin-dependent kinase 4 inhibitor led to significant inhibition of cell growth of the resistant mutants, suggestive of potential alternative treatment strategies. These results identify novel mutations mediating resistance to irreversible EGFR inhibitors and reveal alternative strategies to overcome or prevent the development of resistance in EGFR-mutant non-small cell lung cancers.     

Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial

Depression is one of the most common neuropsychiatric conditions, with a lifetime prevalence approaching 17%. Although a variety of pharmaceutical agents is available for the treatment of depression, psychiatrists find that many patients cannot tolerate the side effects, do not respond adequately, or finally lose their response. On the other hand, many herbs with psychotropic effects have far fewer side effects. They can provide an alternative treatment or be used to enhance the effect of conventional antidepressants. A number of recent preclinical and clinical studies indicate that stigma and petal of Crocus sativus have antidepressant effect. Our objective was to compare the efficacy of petal of C. sativus with fluoxetine in the treatment of depressed outpatients in an 8-week pilot double-blind randomized trial. Forty adult outpatients who met the DSM- IV criteria for major depression based on the structured clinical interview for DSM- IV participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. In this double-blind and randomized trial, patients were randomly assigned to receive capsule of petal of C. sativus 15 mg bid (morning and evening) (Group 1) and fluoxetine 10 mg bid (morning and evening) (Group 2) for a 8-week study. At the end of trial, petal of C. sativus was found to be effective similar to fluoxetine in the treatment of mild to moderate depression (F=0.03, d.f.=1, P=0.84). In addition, in the both treatments, the remission rate was 25%. There were no significant differences in the two groups in terms of observed side effects. The present study is supportive of other studies which show antidepressant effect of C. sativus.     

Correlation of serum prolactin levels and disease activity in systematic lupus erythematosus

To assess the frequency of hyperprolactinaemia and its possible clinical significance in patients with systemic lupus erythematosus (SLE). In this cross-sectional study, we determined serum prolactin (PRL) levels in 60 SLE female patients (age range 15–60 years). Disease activity was defined according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Serum PRL concentrations were determined by immunoradiometric assay. Elevated serum concentrations of PRL (>20 ng/ml) were found in 5 of 60 (8.4%) patients. No direct correlation between PRL levels with disease activity of SLE was found (r = 0.062, P = 0.39). SLE was active in 23 patients (SLEDAI ≥ 6) and inactive in 37 (SLEDAI < 6). In those with active disease, median PRL levels were lower (11.0 ng/ml) than normoprolactinaemic group (12.1 ng/ml). There was no significant difference in serum PRL levels between active and non-active patients (P = 0.07). There was a significant difference in the frequency of several clinical manifestations and serological parameters between SLE patients with normal and high prolactin (renal involvement, haematological manifestation and anti-ds DNA). This study has shown that hyperprolactinaemia is prevalent in random SLE patients. The elevated PRL levels seem not to be associated with disease activity. The mechanism and pathoaetiological and clinical significance of hyperprolactinaemia in a small subset of SLE patients remain unclear and a longer follow-up is necessary.     

A Trial of Discontinuation of Empiric Vancomycin Therapy in Patients with Suspected Methicillin-Resistant Staphylococcus aureus Health Care-Associated Pneumonia

Healthcare-associated pneumonia (HCAP) guidelines recommend de-escalating initial antibiotic therapy based on results from lower-respiratory-tract cultures. In the absence of adequate lower respiratory cultures, physicians are sometimes reluctant to discontinue empirical vancomycin, which is given for suspected methicillin-resistant Staphylococcus aureus (MRSA) HCAP. We evaluated a strategy of discontinuing vancomycin if both nasal and throat cultures were negative for MRSA when lower-respiratory-tract cultures were not available. An antimicrobial stewardship team identified patients receiving empirical vancomycin for suspected or proven HCAP but for whom adequate lower-respiratory-tract cultures were not available. Nasal and throat swab specimens were obtained and plated on MRSA selective media. If both nasal and throat MRSA cultures were negative, the stewardship team recommended discontinuation of empirical vancomycin. Demographic and clinical aspects, a clinical pulmonary infection score (CPIS) on the day of the stewardship recommendation, and mortality of patients for whom vancomycin was discontinued were obtained by retrospective chart review. A convenience sample of 91 patients with nasal and throat cultures negative for MRSA in the absence of adequate respiratory cultures had empirical vancomycin therapy discontinued. A retrospective review revealed that 88 (97%) patients had a CPIS of ≤6 on the day of the stewardship recommendation. In-hospital mortality (7.7%) was similar to that of a previous study of de-escalation of antibiotics in pneumonia patients without adequate cultures. In the absence of adequate lower-respiratory-tract cultures, it is reasonable to discontinue empirical vancomycin HCAP therapy in patients with negative MRSA nasal and throat cultures and a CPIS of <6.     

Inhibitory effect and structure–activity relationship of some Biginelli-type pyrimidines against HSV-1

Inevitable emergence of multi-drug resistant strains to current available drugs makes an impetus for finding new therapeutic agents against herpes simplex virus (HSV). In this study, a series of novel derivatives of Biginelli-type pyrimidines were evaluated as potential anti-HSV-1 compounds by plaque reduction method. The cellular toxicity was assessed by XTT proliferation assay. The time course of anti-HSV activity of the most active compound was studied to show the anti-viral effect in various intervals of replication cycle. Compounds 2, 6, 8, 11, 12, 17, 18, 20, and 40 had the highest activity for inhibition of HSV. Compound 40 inhibited HSV replication with IC₅₀ of 0.9 μmol/l and had CC₅₀ of up to 100 μmol/l. This compound was a noteworthy inhibitor against HSV with TI value of 111. Compound 20 also showed considerable inhibitory activity with IC₅₀ of 1.8 μmol/l. Result of time-of-addition study showed that compound 40 inhibits HSV replication at a stage after entry of virions to the target cells. Analysis of structure of the studied compounds demonstrated clear relationships with their anti-HSV effects. Some of the compounds seem to be promising candidates for future anti-HSV drug discovery researches. Structural manipulation based on the obtained structure–activity relationships would propose some new leads for anti-HSV drug discovery programs.