Sequential Stevens-Johnson syndrome and photo-recall phenomenon.

title: Unresolving furunculosis in a diabetic patient: cutaneous Mycobacterium abscessus infection.
abstract: Dear Editor, Mycobacterium abscessus is a ubiquitous rapidly growing mycobacterium which is widespread in soil, water and dust. It is known to cause cutaneous infections in the form of furuncles, nodules and ulcers. Infections typically develop following trauma such as injections, acupuncture, operations and other penetrating  We describe a diabetic patient who developed multiple furuncles over her abdomen due to an infection with M. abscessus from which several learning points are highlighted.

title: Oral mucous membrane pemphigoid: complete response to topical tacrolimus.
abstract: Mucous membrane pemphigoid includes a heterogeneous group of blistering diseases, which have in common the involvement of the mucosae, a chronic course and a scarring tendency (1–3). The oral mucosa, conjunctiva, and, less frequently, the nose, oesophagus, larynx and genitals may be affected (1–3). Erosions and scarring of the mucosae might result in significant morbidity, and treatment is usually challenging. We report here a case of oral mucous membrane pemphigoid that was treated successfully with oral rinses of topical tacrolimus.

title: Initial presentation of DRESS: often misdiagnosed as infections.
abstract: related adverse effects, including edema, urticaria, vesicles, erosions, dermatitis, and lymphadenopathy were seen in 58 children (54%). Thirteen percent of children discontinued treatment after 2 months owing to a variety of factors, including adverse effects, difficulties commuting to the treatment center, and/or the disruption caused by weekly absences from school. Fourteen patients showed complete hair regrowth after 6 months of treatment (13%); 27 had partial regrowth (25%). At 12 months, 12 patients had complete hair regrowth (11%), and 23 had partial regrowth (21%). The remainder did not experience any hair growth or stopped treatment (Table 1). Twelve patients 10 years or younger had marked sensitization reactions (32%) compared with 11 patients aged 11 to 18 years (16%) (P=.07) . Twenty-seven of 38 patients younger than 10 years had adverse effects during DPCP treatment (71%) compared with 31 of 70 patients aged 11 to 18 years (44%) (P=.01). None of the known prognostic factors, including age at onset, extent of involvement, atopy, coexistent autoimmune disease, family history, ophiasis pattern, or nail involvement, was associated with greater likelihood of having partial or complete response to DPCP therapy (data not shown).

title: Therapy-related leukemia cutis after adjuvant chemotherapy in a breast cancer patient.

title: FOXO3a turns the tumor necrosis factor receptor signaling towards apoptosis through reciprocal regulation of c-Jun N-terminal kinase and NF-kappaB.
abstract: We evaluated the full range effects of FOXO3a in endothelial cells (ECs) by microarray analysis and investigated the role of FOXO3a regulating TNF receptor signaling pathway.



Human umbilical vein endothelial cells (HUVECs) were transfected with adenoviral vectors expressing constitutively active FOXO3a (Ad-TM-FOXO3a). Ad-TM-FOXO3a transfection caused remarkable apoptosis, which were accompanied with upregulation of genes related with TNF receptor signaling, such as TNF-alpha, TANK (TRAF-associated NF-kappaB activator), and TTRAP (TRAF and TNF receptor-associated protein). Furthermore, kappaB-Ras1 (IkappaB-interacting Ras-like protein-1) which is known to block IkappaB degradation was found increased, and intranuclear translocation of NF-kappaB was inhibited. GADD45beta and XIAP, negative regulators of c-Jun N-terminal kinase (JNK), were suppressed and JNK activity was increased. Attenuation of TNF signaling pathway either by blocking antibody for TNF receptor or by blocking JNK with DMAP (6-dimethylaminopurine) or Ad-TAM67 (dominant negative c-Jun) cotransfection, significantly reduced FOXO3a-induced apoptosis. Finally, treatment of vasculature with heat shock, an activator of endogenous FOXO3a, resulted in EC apoptosis, which was completely rescued by Ad-TAM67.



FOXO3a promotes apoptosis of ECs, through activation of JNK and suppression of NF-kappaB. These data identify a novel role of FOXO3a to turn TNF receptor signaling to a proapoptotic JNK-dependent pathway.

title: Imipenem heteroresistance induced by imipenem in multidrug-resistant Acinetobacter baumannii: mechanism and clinical implications.
abstract: Acinetobacter baumannii has emerged as a major pathogen causing nosocomial infections, particularly in critical patients admitted to the Intensive Care Unit. Increasing resistance to carbapenems in A. baumannii has been observed worldwide. Here we report the clinical impact and mechanism of imipenem heteroresistance (imipenem minimum inhibitory concentration of 6-32 μg/mL with the presence of resistant cells inside the inhibition zone of Etest strips or disks) in multidrug-resistant A. baumannii (MDR-AB). To identify risk factors associated with the emergence of imipenem heteroresistance, a retrospective case-control study was undertaken involving cases with subsequent clinical isolates of the same genotype showing loss of imipenem susceptibility and matched controls with isolates belonging to imipenem-susceptible MDR-AB. The molecular mechanism of heteroresistance was examined. From April 2006 to March 2007, 126 consecutive isolates of MDR-AB were identified from 29 patients. Switch from imipenem susceptibility to heteroresistance was more likely to occur in successive MDR-AB derived from patients who had been exposed to imipenem (length of use 10.9 ± 6.5 days for cases vs. 5.3 ± 4.8 days for controls; P=0.02). An insertion sequence (ISAba1) was found in the promoter region of a class C β-lactamase gene (bla(ADC-29)) in most imipenem-heteroresistant MDR-AB isolates. In vitro experiments indicated that imipenem heteroresistance, which was associated with overexpression of bla(ADC-29), could be induced by imipenem. Carbapenem use was the only risk factor identified for the emergence of carbapenem-heteroresistant MDR-AB. Physicians should weigh the benefits and risks of each carbapenem-based treatment in managing carbapenem-susceptible MDR-AB infection.

title: Aging and arterial stiffness.
abstract: Arterial walls stiffen with age. The most consistent and well-reported changes are luminal enlargement with wall thickening and a reduction of elastic properties at the level of large elastic arteries. Longstanding arterial pulsation in the central artery causes elastin fiber fatigue and fracture. Increased vascular calcification and endothelial dysfunction are also characteristic of arterial aging. These changes lead to increased pulse wave velocity, especially along central elastic arteries, and increases in systolic blood pressure and pulse pressure. Vascular aging is accelerated by coexisting cardiovascular risk factors, such as hypertension, metabolic syndrome and diabetes. Vascular aging is an independent risk factor for cardiovascular disease, from atherosclerosis to target organ damage, including coronary artery disease, stroke and heart failure. Various strategies, especially controlling hypertension, show benefit in preventing, delaying or attenuating vascular aging.

title: Rhabdoid Tumor of the Kidney Is a Component of the Rhabdoid Predisposition Syndrome 

abstract: The rhabdoid predisposition syndrome (RPS) is characterized by pedigrees in which two or more individuals carry germline mutations of the hSNF5/INI1 tumor suppressor gene. The tumors associated with the syndrome include atypical teratoid/rhabdoid tumor (AT/RT), choroid plexus carcinoma, medulloblastoma, and extrarenal rhabdoid tumor. Rhabdoid tumor of the kidney (RTK) has not been described as part of the RPS. We report a case of a 7-month-old boy with RTK whose sister had a malignant cerebellar tumor followed by a malignant lung and pleural tumor of childhood with typical rhabdoid histology. Molecular genetic analysis of the RTK and tissue from the pleural tumor revealed in both cases identical nonsense mutations of the hSNF5/INI1 gene on chromosome 22q11.2, where thymidine was substituted for cytosine in base 472. The proband had an identical germline mutation. This is the fifth genetically analyzed RPS pedigree and the first to include an RTK.

title: Apolipoprotein CIII Overexpressing Mice Are Predisposed to Diet-Induced Hepatic Steatosis and Hepatic Insulin Resistance
abstract: Nonalcoholic fatty liver disease (NAFLD) and insulin resistance have recently been found to be associated with increased plasma concentrations of apolipoprotein CIII (APOC3) in humans carrying single nucleotide polymorphisms within the insulin response element of the APOC3 gene. To examine whether increased expression of APOC3 would predispose mice to NAFLD and hepatic insulin resistance, human APOC3 overexpressing (ApoC3Tg) mice were metabolically phenotyped following either a regular chow or high-fat diet (HFD). After HFD feeding, ApoC3Tg mice had increased hepatic triglyceride accumulation, which was associated with cellular ballooning and inflammatory changes. ApoC3Tg mice also manifested severe hepatic insulin resistance assessed by a hyperinsulinemic-euglycemic clamp, which could mostly be attributed to increased hepatic diacylglycerol content, protein kinase C-ε activation, and decreased insulin-stimulated Akt2 activity. Increased hepatic triglyceride content in the HFD-fed ApoC3Tg mice could be attributed to a ≍70% increase in hepatic triglyceride uptake and ≍50% reduction hepatic triglyceride secretion.  These data demonstrate that increase plasma APOC3 concentrations predispose mice to diet-induced NAFLD and hepatic insulin resistance. (Hepatology 2011;54:1650-1660)