Acute generalized exanthematous pustulosis: a retrospective analysis showing a clear predilection for women

The clinical reaction pattern acute generalized exanthematous pustulosis is increasingly recognized today as drug intake details are more meticulously recorded and diagnostic guidelines are formulated. Nevertheless, the diagnosis and etiology remain unclear. This examination of the clinical and histologic features of acute generalized exanthematous pustulosis, undertaken in a retrospective study of 13 patients in an urban medical center, was aimed at determining the underlying mechanism of the etiology of the disease. Findings include a female predominance and the overwhelming prevalence of acetaminophen as the culprit agent, adding two more components to what is known about acute generalized exanthematous pustulosis. The possible mechanisms of the disease are discussed, enlightened by its appearance in two women in the study who were pregnant when the reaction first erupted.     

Fat cell-derived modulators of vascular cell pathophysiology: the list keeps growing

Independent of the association of obesity with dyslipidemia, hypertension, and increased propensity for diabetes, fatness per se is increasingly recognized as a cardiovascular offender. That adipose tissue releases a wide range of adipokines, growth factors, enzymes, and enzyme substrates linked to vascular injury provides a plausible explanation for the role of fat in vascular disease: tumor necrosis factor-alpha, leptin, resistin, interleukin-1, -6, -8, and -18, serum amyloid A, monocyte chemoattractant protein I, macrophage inhibitory factor, aortic carboxypeptidase, hepa-rin-binding epidermal growth factor-like growth factor, vascular endothelial growth factor, transforming growth factor beta, angiotensinogen, cathepsin S, estradiol, cortisol, mineralocorticoid releasing factor, and calcitonin peptides are probable fat-derived prothrombotic, proinflammatory, and proatherosclerotic agents acting in a paracrine and/or endocrine manner. Other adipocyte products such as adiponectin, transforming growth factor beta, and interleukin-10 exert some antiatherogenic effects. The following is a short overview of how adipose tissue products affect the vasculature.     

Perivascular fat: innocent bystander or active player in vascular disease?

Although nearly all arteries are surrounded by perivascular fat, its role in vascular function and disease is clearly understudied. At least one type of perivascular fat, epicardial adipose tissue, appears to be related to both weight and age and tends to express proatherogenic/proinflammatory products in subjects with cardiovascular disease. Perivascular fat may evolve from primordial cells in the adventitia or from circulating precursors migrating through the arterial wall. Once deposited periarterially, adipose tissue may release locally a large number of products, which potentially interact with the arterial wall. Additionally, the authors propose that perivascular fat, per se, may attract circulating monocytes through the release of chemokines such as monocyte chemoattractant protein-1. Some of the macrophages traversing the arterial wall en route to the perivascular fat may be redirected and eventually populate the arterial wall itself, thereby enhancing vascular inflammatory processes and accelerating atherosclerosis.     

The clinical significance of isolation of two different organisms from the urine of patients with an indwelling catheter

Background

We evaluated the clinical significance of urine cultures from patients with an indwelling urinary catheter (UC) from which 2 different pathogens were isolated.

Methods

Urine cultures from patients with a UC from which 2 different organisms were isolated were randomly divided into a control group (culture results were reported as usual) and a study group (culture results were reported as “mixed growth”). Endpoints included change in antibiotic treatment, use of broad spectrum agents, time for clinical improvement, and duration of admission.

Results

A total of 81 cultures met the inclusion criteria. Antibiotic treatment was changed after 72–96 h in 19 (48%) study patients and in 25 (61%) controls (NS). There was no difference regarding narrowing or broadening of antibiotic spectrum, and duration of hospitalization was similar. In each group, 15 (36%) patients died.

Conclusion

Our findings imply that laboratory work-up of 2 pathogens from patients with an indwelling catheter may be discarded.     

Multidisciplinary Treatment of the Metabolic Syndrome Lowers Blood Pressure Variability Independent of Blood Pressure Control

Blood pressure (BP) variability (BPV) contributes to target organ damage independent of BP. The authors examined the effect of a 1‐year multidisciplinary intervention on BPV in patients with the metabolic syndrome (MetS) as defined by criteria from the Third Report of the Adult Treatment Panel. Forty‐four nondiabetic patients underwent clinical and biochemical profiling, 24‐hour ambulatory BP monitoring (ABPM), body composition, carotid intima‐media thickness, and carotid‐femoral pulse wave velocity (PWV). The intervention targeted all MetS components. BPV was assessed by the standard deviation of daytime systolic BP derived from ABPM. Patients with low and high BPV (lower or higher than the median daytime standard deviation of 11.6 mm Hg) did not differ in regards to systolic and diastolic BP, age, fasting glucose, glycated hemoglobin, and body mass index, but the high‐variability group had higher values of low‐density lipoprotein and leg fat. The 1‐year intervention resulted in weight reduction but not BP‐lowering. BPV declined in the high‐variability group in association with lowering of PWV, C‐reactive protein, glycated hemoglobin, alanine aminotransferase, asymmetric dimethylarginine, and increased high‐density lipoprotein cholesterol. A multidisciplinary intervention independent of BP‐lowering normalized BPV, lowered PWV, and enhanced metabolic control.     

Q fever endocarditis; not always expected

Q fever endocarditis is a chronic disease with protean manifestations. The clinical and serological manifestations of nine patients diagnosed as having Q fever endocarditis during a 19-year period are reviewed. Four patients (44%) required valve replacement due to congestive heart failure. Three of these four patients were diagnosed as having Q fever endocarditis only after elective valve surgery, by histopathological examination of the valve and subsequent serological tests. Prior to surgery they were afebrile and had no other symptom or sign indicative of endocarditis. The antibiotic treatment and the decreasing titres of Q fever antibodies of all nine patients during several years of follow-up are summarized. Careful assessment of heart valves for histopathological evidence of inflammation is suggested, even after elective replacement. If found, clinical and laboratory evaluation should include determination of anti-Coxiella burnetti antibodies.     

iRhom2 regulates CSF1R cell surface expression and non‐steady state myelopoiesis in mice

CSF1R (colony stimulating factor 1 receptor) is the main receptor for CSF1 and has crucial roles in regulating myelopoeisis. CSF1R can be proteolytically released from the cell surface by ADAM17 (A disintegrin and metalloprotease 17). Here, we identified CSF1R as a major substrate of ADAM17 in an unbiased degradomics screen. We explored the impact of CSF1R shedding by ADAM17 and its upstream regulator, inactive rhomboid protein 2 (iRhom2, gene name Rhbdf2), on homeostatic development of mouse myeloid cells. In iRhom2‐/‐ mice, we found constitutive accumulation of membrane‐bound CSF1R on myeloid cells at steady state, although cell numbers of these populations were not altered. However, in the context of mixed bone marrow (BM) chimera, under competitive pressure, iRhom2‐/‐ BM progenitor‐derived monocytes, tissue macrophages and lung DCs showed a repopulation advantage over those derived from wild‐type (WT) BM progenitors, suggesting enhanced CSF1R signaling in the absence of iRhom2. In vitro experiments indicate that iRhom2‐/‐ Lin^?SCA‐1⁺c‐Kit⁺ (LSKs) cells, but not granulocyte‐macrophage progenitors (GMPs), had faster growth rates than WT cells in response to CSF1. Our results shed light on an important role of iRhom2/ADAM17 pathway in regulation of CSF1R shedding and repopulation of monocytes, macrophages and DCs.