Hormonal substitution during menopause: what are we treating?

OBJECTIVES: It is suggested that during menopausal transition, women with vasomotor symptoms benefit from HRT, (hormone replacement therapy) whereas, the use of HRT for other cognitive-vegetative symptoms is questionable. METHODS: The occurrence of menopausal complaints and depressive symptoms was assessed cross-sectionally in 5896 Dutch Caucasian women (47-54 years) of a large community sample in the city of Eindhoven, The Netherlands. Menopausal complaints were assessed using a 22 items self-rating scale (consisting of a vasomotor, uro-genital and a cognitive-vegetative subscale). Depressive symptoms were assessed using the Edinburgh depression scale (EDS). Differences in mean scores were analysed between groups using ANOVA. The independent relationship of depressive symptoms to the intensity of menopausal complaints was assessed, by multiple linear regression analysis. RESULTS: Women using HRT showed the highest scores on all subscales. Oral contraceptive users had significantly lower scores on the vasomotor subscale compared to HRT users and to non users. Depressive symptoms contributed the most, to the explained variance on scores on the menopausal subscales. CONCLUSIONS: Women during menopause presenting several complaints, other than vasomotor origin might be suffering from underlying depression which makes it questionable to prescribe HRT for the latter symptoms.     

New Delhi metallo-β-lactamase (NDM-1)-producing Klebsiella pneumoniae: case report and laboratory detection strategies

The spread of antimicrobial resistance among Enterobacteriaceae is a significant clinical threat. We report the first case of an Enterobacteriaceae strain harboring the NDM-1 metallo-β-lactamase in a pediatric patient in the United States. We describe strategies for the detection of this novel resistance mechanism encountered in an isolate of Klebsiella pneumoniae.     

Chronic inflammation-enhanced atherosclerosis: can we consider it as a new clinical syndrome?

Incidence of cardiovascular disease in patients with chronic autoimmune disorder like rheumatoid arthritis is much higher than in general population. Cardiovascular events (e.g. myocardial infarction or stroke) are caused by premature accelerated development of atherosclerosis. Chronic inflammation-enhanced atherosclerosis syndrome is proposed as a separate syndrome occurring in patients suffering of chronic inflammation. It is suggested that atherosclerosis as an inflammatory disease and long-lasting extravascular inflammation have common mechanisms resulting in an increase in atherosclerosis and its sequellae, cardiovascular diseases.     

Outbreak of Colistin-Resistant,Carbapenemase-Producing Klebsiella pneumoniae: Are We at the End of the Road?

Carbapenem-resistant Klebsiella pneumoniae strains that produce K. pneumoniae carbapenemase (KPC) have spread globally in the last decade. Colistin is a key agent in treating infections caused by this pathogen. In this issue of the Journal of Clinical Microbiology, Giani et al. (T. Giani, F. Arena, G. Vaggelli, V. Conte, A Chiarell, L. H. De Angelis, R. Fornaini, M. Grazzini, F. Niccolini, P. Pecile, and G. M. Rossolini, J Clin Microbiol 53:3341–3344, 2015, http://dx.doi.org/10.1128/JCM.01017-15) describe a sustained outbreak of colistin-resistant KPC-producing K. pneumoniae.     

Elevated homocysteine levels: What inborn errors of metabolism might we be missing?

Elevated total plasma homocysteine (hyperhomocysteinemia) is a marker of cardiovascular, thrombotic, and neuropsychological disease. It has multiple causes, including the common nutritional vitamin B12 or folate deficiency. However, some rare but treatable, inborn errors of metabolism (IEM) characterized by hyperhomocysteinemia can be missed due to variable presentations and the lack of awareness. The aim of this study is to identify undiagnosed IEM in adults with significantly elevated homocysteine using key existing clinical data points, then IEM specific treatment can be offered to improve outcome. We conducted a retrospective study with data mining and chart review of patients with plasma total homocysteine >30 μmol/L over a two-year period. We offer biochemical and genetic testing to patients with significant hyperhomocysteinemia without a clear explanation to diagnose IEM. We identified 22 subjects with significant hyperhomocysteinemia but no clear explanation. Subsequently, we offered genetic testing to seven patients and diagnosed one patient with classic homocystinuria due to cystathionine beta-synthase deficiency. With treatment, she lowered her plasma homocysteine and improved her health. This study stresses the importance of a thorough investigation of hyperhomocysteinemia in adults to identify rare but treatable IEM. We propose a metabolic evaluation algorithm for elevated homocysteine levels.     

The epidemiology of the first described carbapenem-resistant Klebsiella pneumoniae outbreak in a tertiary care hospital in Saudi Arabia: how far do we go?

The purpose of this investigation was to describe the first documented carbapenem-resistant Klebsiella pneumoniae (CRKP) outbreak in a tertiary care facility in Saudi Arabia. We initiated a prospective study to follow all cases of CRKP as well as the active surveillance of patients in areas where cases were identified. We also conducted a retrospective review of the microbiology database for any missed cases of CRKP. Pulsed field gel electrophoresis (PFGE) was conducted for the available CRKP isolates. During March 2010, a cluster of eight CRKPs was detected primarily in the adult intensive care unit (ICU). Patients with CRKPs were put under strict contact isolation, along with appropriate infection control measures. A retrospective review of K. pneumoniae isolates over the previous 6 months revealed two more CRKPs. The PFGE results during the outbreak period showed that the majority of strains were genetically indistinguishable or closely related. The majority of patients had prolonged hospital stay (91%), indwelling devices (81%), surgical procedures (74%), carbapenem use (62%), and colonization/infection with other multiple drug-resistant organisms (MDROs) (57%). Two-fifths of patients with CRKP had clinical infection and 38% died during the current hospitalization. Contact isolation, hand hygiene, environmental cleaning, and staff education may control CRKP outbreak in the acute care setting, but did not prevent endemicity.     

Thiopurines and myeloid disorders: is more caution needed when treating inflammatory bowel disease patients?

Thiopurines remain the backbone therapy of inflammatory bowel diseases (IBD). However, these drugs have potential mutagenic and carcinogenic effects, especially when prescribed for a long time. In addition to the increased risk of lymphoma and non-melanoma skin cancer, recent data suggest that risk of myeloid disorder is increased in IBD patients with past exposure to thiopurines. Even if individual risk is low, practitioners who take care of IBD patients should be aware of this potential complication of thiopurines treatment.     

Who and when should we screen for prostate cancer? Interviews with key opinion leaders

Prostate cancer screening using prostate-specific antigen (PSA) is highly controversial. In this Q & A, Guest Editors for BMC Medicine’s ‘Spotlight on Prostate Cancer’ article collection, Sigrid Carlsson and Andrew Vickers, invite some of the world’s key opinion leaders to discuss who, and when, to screen for prostate cancer. In response to the points of view from the invited experts, the Guest Editors summarize the experts’ views and give their own personal opinions on PSA screening.     

Histone deacetylase inhibitors: can we consider potent anti-neoplastic agents for the treatment of asthma?

Histone deacetylase inhibitors have emerged as a new class of anti-cancer therapeutics due to their potent anti-proliferative and apoptotic effects in malignant cells. Accumulating evidence is indicating that histone deacetylase inhibitors may also have potential clinical utility in non-oncological applications, including asthma. However, the potential of histone deacetylase inhibitors in asthma remains controversial. For example, the mechanisms of action of the broad-spectrum histone deacetylase inhibitor, Trichostatin A, in animal models of allergic airways disease are conflicting. Further, there is evidence suggesting potential problems associated with histone deacetylase 2 inhibition and conventional glucocorticosteroid therapy. Similarly, disparate findings are emerging following modulation of the class III, sirtuin 1 enzyme. Indeed, it is becoming apparent that the mechanism of action may not be related to histone deacetylase inhibition activity per se. Further, there is only limited evidence that these compounds possess anti-inflammatory effects in models of asthma. In this review, we provide an overview of the biology of the metal-dependent and sirtuin deacetylases in the context of asthma. The controversies surrounding the potential use of histone deacetylase inhibitors in asthma are discussed and future directions involving the investigation of more specific analogues are explored.     

.VO2max: what do we know, and what do we still need to know?

Maximal oxygen uptake (.VO(2,max)) is a physiological characteristic bounded by the parametric limits of the Fick equation: (left ventricular (LV) end-diastolic volume--LV end-systolic volume) x heart rate x arterio-venous oxygen difference. 'Classical' views of .VO(2,max) emphasize its critical dependence on convective oxygen transport to working skeletal muscle, and recent data are dispositive, proving convincingly that such limits must and do exist. 'Contemporary' investigations into the mechanisms underlying peripheral muscle fatigue due to energetic supply/demand mismatch are clarifying the local mediators of fatigue at the skeletal muscle level, though the afferent signalling pathways that communicate these environmental conditions to the brain and the sites of central integration of cardiovascular and neuromotor control are still being worked out. Elite endurance athletes have a high .VO(2,max) due primarily to a high cardiac output from a large compliant cardiac chamber (including the myocardium and pericardium) which relaxes quickly and fills to a large end-diastolic volume. This large capacity for LV filling and ejection allows preservation of blood pressure during extraordinary rates of muscle blood flow and oxygen transport which support high rates of sustained oxidative metabolism. The magnitude and mechanisms of cardiac phenotype plasticity remain uncertain and probably involve underlying genetic factors, as well as the length, duration, type, intensity and age of initiation of the training stimulus.     

Can we see PIP(3) and hydrogen peroxide with a single probe?

A genetically encoded sensor for parallel measurements of phosphatidylinositol 3-kinase activity and hydrogen peroxide (H(2)O(2)) levels (termed PIP-SHOW) was developed. Upon elevation of local phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) concentration, the sensor translocates from the cytosol to the plasma membrane, while a ratiometric excitation change rapidly and simultaneously reports changes in the concentration of H(2)O(2). The dynamics of PIP(3) and H(2)O(2) generation were monitored in platelet-derived growth factor-stimulated fibroblasts and in T-lymphocytes after formation of an immunological synapse. We suggest that PIP-SHOW can serve as a prototype for many fluorescent sensors with combined readouts.     

Rapid and Simultaneous Detection of Genes Encoding Klebsiella pneumoniae Carbapenemase (blaKPC) and New Delhi Metallo-β-Lactamase (blaNDM) in Gram-Negative Bacilli

We present a duplex, real-time PCR assay for detection of Klebsiella pneumoniae carbapenemase (bla_KPC) and New Delhi metallo-β-lactamase (bla_NDM) genes. Accuracy was assessed with 158 Gram-negative bacillary isolates, including 134 carbapenemase producers. The assay had 100% sensitivity and specificity compared with reference methods and a turnaround time of 90 min.