Citations

Abstract Monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma (MM), is one of the most common premalignant conditions in the general population. The cause of MGUS is largely unknown. Recent studies show that there is an increased prevalence of MGUS in blood relatives of persons with lymphoproliferative and plasma cell proliferative disorders, suggesting presence of shared underlying genetic influences. In the past few years, additional studies have examined risk factors and biologic characteristics that may contribute to the increased prevalence of MGUS among relatives of probands with MGUS, MM, and other blood malignancies. This article reviews the known epidemiology and risk factors for familial MGUS and myeloma, the risk of lymphoproliferative disorders and other malignancies among blood-relatives of patients with MGUS and MM, and discusses future directions for research.

OBJECTIVE To test whether diabetic polyneuropathies (DPNs), retinopathy, or nephropathy is more prevalent in subjects with impaired glycemia (IG) (abnormality of impaired fasting glucose [IFG], impaired glucose tolerance [IGT], or impaired HbA1c [IA1C]) than in healthy subjects (non-IG). RESEARCH DESIGN AND METHODS Matched IG and non-IG volunteers were randomly identified from population-based diagnostic and laboratory registries, restudied, and reclassified as non-IG (n = 150), IG (n = 174), or new diabetes (n = 218). RESULTS Frequency (%) of DPN in non-IG, IG, and new diabetes was 3 (2.0%), 3 (1.7%), and 17 (7.8%) narrowly defined (no other cause for polyneuropathy) and 19 (12.7%), 22 (12.6%), and 38 (17.4%) broadly defined. Mean and frequency distribution of composite scores of nerve conduction and quantitative sensation tests were not significantly different between IG and non-IG but were worse in new diabetes. Frequency of retinopathy and nephropathy was significantly increased only in new diabetes. In secondary analysis, small but significant increases in retinopathy and nephropathy were found in IGT, IFG, and IGT combined groups. CONCLUSIONS In population studies of Olmsted County, Minnesota, inhabitants, prevalence of typical DPN, retinopathy, and nephropathy was significantly increased only in subjects with new diabetes—not in subjects with IG as defined by American Diabetes Association (ADA) criteria of abnormality of IFG, IGT, or IA1C. For atypical DPN, such an increase was not observed even in subjects with new diabetes. In medical practice, explanations other than IG should be sought for patients with atypical DPN (chronic idiopathic axonal polyneuropathy) who have IG.

SummaryBackgroundTapentadol is a mu‐opioid receptor agonist and norepinephrine reuptake inhibitor. In clinical trials, tapentadol provided somatic pain relief comparable to mu‐opioids such as oxycodone, with significantly less gastrointestinal adverse effects. The acute effects of tapentadol on gastrointestinal and colonic transit are unclear.AimTo compare acute effects of oral tapentadol and oxycodone on gastric, small bowel and colonic transit of solids in 38 healthy human subjects.MethodsIn a randomised, parallel‐group, double‐blind, placebo‐controlled study of the effects of identical‐appearing tapentadol immediate release (IR), 75 mg t.d.s., or oxycodone IR, 5 mg t.d.s., for 48 h, we measured gastric (GE), small bowel (SBT measured as colonic filling at 6 h) and colonic transit by validated scintigraphy. Drug was commenced on the evening before the start of the transit test. The primary endpoints were overall colonic transit (geometric centre, GC) at 24 h and GE half‐time (t1/2). ancova of transit data included gender or BMI as covariates. Adverse effects were summarised.ResultsAt the doses tested, oxycodone and tapentadol significantly delayed GE t1/2 and SBT, but not overall colonic transit, compared to placebo. Transit profiles in all regions were not significantly different between oxycodone and tapentadol at the doses tested. Both oxycodone and tapentadol were associated with nausea and central effects attributable to central opiate effects.ConclusionsTapentadol significantly delayed gastric emptying t1/2 and small bowel transit, similar to oxycodone. These data suggest that acute administration of tapentadol may not have significant advantages over standard mu‐opioids, in terms of the potential to avoid upper gastrointestinal motor dysfunction.

Abstract Calcium-modulating cyclophilin ligand (CAML) is a ubiquitously expressed protein that is important during thymopoiesis. However, whether it serves a function in mature lymphocytes is unknown. In this article, we show that CAML is essential for survival of peripheral follicular (Fo) B cells. Conditional deletion of CAML in CD19-Cre transgenic mice caused a significant reduction in Fo cell numbers and increased rates of homeostatic proliferation. CAML-deficient Fo cells showed increased cellular turnover and normal proliferative ability. Although CAML-deficient Fo cells responded to AgR stimulation and to B cell activating factor, they displayed decreased survival and increased apoptosis following stimulation with LPS and IL-4 in vitro. Failure to survive was not due to aberrant B cell development in the absence of CAML, because induced deletion of the gene in mature cells resulted in a similar phenotype. These data establish an essential and ongoing role for CAML in the long-term survival of mature B cells.

Benign tumors of the esophagus are uncommon, representing <0.5% of esophageal tumors. Fibrolipomas are a subset of benign fibrovascular tumors, which present with dysphagia, odynophagia, and substernal fullness. These intraluminal tumors can become elongated and molded into a long pedunculated polyp by constant peristaltic movements. They can cause esophageal obstruction if large and long enough and can cause asphyxiation if they become lodged into the glottis. A barium swallow is the main diagnostic tool; treatment is surgical via a transoral, transcervical, or transthoracic approach. We report the excision of a large esophageal fibrolipoma through a transoral laser microsurgical approach.

AbstractThe Na+/H+ exchanger regulatory factor-2 (NHERF-2) is an integral component of almost all endothelial cells (ECs), yet its endothelial function is not known. Here, we found that NHERF-2, is a key regulator of endothelial homeostasis because NHERF-2–silenced ECs proliferate at a much higher rate even in the absence of mitogens such as VEGF compared with control ECs. We further show that the hyperproliferation phenotype of NHERF-2–silenced EC is because of an accelerated cell cycle that is probably caused by a combination of the following factors: increased cytoplasmic calcium, increased expression of c-Myc, increased expression of cyclin D1, and reduced expression of p27. Using an experimental mouse model of human hemangioma, we found that the endothelial neoplasms derived from NHERF-2–silenced cells were much larger in volume than those derived from control cells. Thus, NHERF-2 is a negative regulator of endothelial proliferation and may have important roles in endothelial homeostasis and vascular modeling.