Primary lymph node plasmacytomas (plasmacytic lymphomas)

To determine whether primary lymph node plasmacytoma (PLNP) is a distinct entity among other types of plasma cell neoplasia, we analyzed a large series of PLNPs from 2 large lymphoma registries to compare histologic, immunophenotypic, and clinical features of PLNPs, nonnodal extramedullary plasmacytomas, and multiple myeloma. Twenty-five PLNPs (clinical data on 15 cases) were compared with 10 non-lymph node plasmacytomas and 51 cases of multiple myeloma; 36 cases of reactive plasmacytoses were used as controls. The histologic features of PLNP and other extramedullary plasmacytomas were similar. The histologic features of PLNPs were more immature than those of reactive plasmacytoses and less immature than in multiple myeloma. The immunophenotype of PLNPs significantly differed from that of reactive plasmacytoses, other extramedullary plasmacytomas, and multiple myeloma. PLNPs did not progress to multiple myeloma, unlike other extramedullary plasmacytomas, even though survival in PLNPs and other extramedullary plasmacytomas was similar. Our findings suggest that PLNPs may be distinct from other plasma cell dyscrasias.     

Astrogliosis is delayed in type 1 interleukin-1 receptor-null mice following a penetrating brain injury

The cytokines IL-1α and IL-1β are induced rapidly after insults to the CNS, and their subsequent signaling through the type 1 IL-1 receptor (IL-1R1) has been regarded as essential for a normal astroglial and microglial/macrophage response. To determine whether abrogating signaling through the IL-1R1 will alter the cardinal astrocytic responses to injury, we analyzed molecules characteristic of activated astrocytes in response to a penetrating stab wound in wild type mice and mice with a targeted deletion of IL-1R1. Here we show that after a stab wound injury, glial fibrillary acidic protein (GFAP) induction on a per cell basis is delayed in the IL-1R1-null mice compared to wild type counterparts. However, the induction of chondroitin sulfate proteoglycans, tenascin, S-100B as well as glutamate transporter proteins, GLAST and GLT-1, and glutamine synthetase are independent of IL-1RI signaling. Cumulatively, our studies on gliosis in the IL-1R1-null mice indicate that abrogating IL-1R1 signaling delays some responses of astroglial activation; however, many of the important neuroprotective adaptations of astrocytes to brain trauma are preserved. These data recommend the continued development of therapeutics to abrogate IL-1R1 signaling to treat traumatic brain injuries. However, astroglial scar related proteins were induced irrespective of blocking IL-1R1 signaling and thus, other therapeutic strategies will be required to inhibit glial scarring.     

Two-dimensional gel electrophoresis as an aid in the analysis of monoclonal gammopathies

Two-dimensional gel electrophoresis is the most powerful protein separation technique currently available. In the authors' laboratory it has proved useful in the analysis of specimens from patients with monoclonal gammopathies when those specimens were otherwise difficult to diagnose. Examples of problematic specimens include biclonal gammopathies, heavy chain diseases, and monoclonal gammopathies that show a small or invisible spike on serum protein electrophoresis on cellulose acetate. In addition, two-dimensional electrophoresis is being used to investigate the pathophysiologic features of myeloma kidney disease, especially regarding potential interactions of Bence Jones proteins and kidney proteins.     

Increased prooxidant production and enhanced susceptibility to glutathione depletion in HepG2 cells co-expressing HCV core protein and CYP2E1

Hepatitis C virus (HCV) and HCV core protein are hypothesized to induce hepatic oxidative stress and exacerbate injury caused by other toxins such as ethanol that induce the cytochrome P450 enzyme, CYP2E1. In the current study, the effects of HCV core protein [sequence genotype 1b, (nt 342-915)] on parameters indicative of oxidative stress were evaluated in HepG2 cells stably over expressing CYP2E1 (E47), or vector controls (C34). Stable (>10 passages) expression of HCV core protein and CYP2E1 was confirmed in clonal cell lines at the level of mRNA and immunoreactive protein. Prooxidant production, as determined by cellular oxidation of dichlorodihydrofluorescin and dihydroethidium (HE), was increased by expression of HCV core protein in the presence or absence of CYP2E1. Depletion of glutathione (GSH) with buthionine sulfoximine (BSO) enhanced prooxidant production in both C34 and E47 cells. In addition, prooxidant production was greater in BSO-treated cells expressing HCV core protein, and this effect was further enhanced in cells expressing both HCV core and CYP2E1. The CYP2E1 inhibitor, 4-methylpyrazole, could suppress increased prooxidant production in E47 cells. Finally, cells co-expressing both CYP2E1 and HCV core protein showed significantly decreased viability following GSH depletion. These studies show simultaneous expression of HCV core protein and CYP2E1 increases parameters indicative of oxidative stress as well as sensitization to cell injury induced by GSH depletion. These results support the hypothesis that enhanced injury in hepatocytes over expressing both HCV core protein and CYP2E1 is mediated by increases in oxidative stress.     

Correlation of initial food reactions to observed reactions on challenges.

BACKGROUND: Food allergies occur in 2% to 3% of the pediatric population. These reactions can vary from mild cutaneous manifestations to severe life-threatening reactions. Limited information is available on which specific factors may predict the severity of subsequent reactions. OBJECTIVE: To determine whether the organ system or the specific food involved in the initial allergic reaction predicts the outcome of subsequent food challenge. METHODS: Retrospective review of all food sensitive children who underwent food challenges at The Children's Hospital of Philadelphia, Philadelphia, PA, in a 5-year period (n = 998 challenges). The specific food, initial symptom on presentation, and reaction on open challenges were recorded. RESULTS: A total of 413 of 998 food challenges produced positive results. Milk, egg, and peanut were the most common foods to be associated with a positive challenge result. The most common presentation of food allergy was cutaneous followed by multiorgan reactions. Peanut, milk, and egg sensitivities were more likely to cause a multiple-organ system reaction on challenge than wheat or other foods. Patients with egg allergy were more likely to have a different reaction on rechallenge than other foods. CONCLUSIONS: Milk, egg, and peanut are the most common foods associated with food challenges. Patients will typically experience similar reaction on re-exposure to the initial reaction. However, multiple-organ system reactions can occur after any initial clinical presentation, with milk, egg, and peanut having more multiple-organ reactions than other foods.     

Does noncontact low‐frequency ultrasound therapy contribute to wound healing at the molecular level?

Noncontact low‐frequency ultrasound (NLFU) is used to treat various types of chronic wounds including venous, diabetic, and pressure ulcers. The objective for this substudy of the IN BALANCE RCT VLU trial was to characterize and compare the NLFU treatment group and patients receiving standard of care (SOC) with respect to the effect of the assigned study treatment on content/quantity of inflammatory cytokines and fibrinogen as well as bacteria. Higher mean wound area reduction was observed in the NLFU treatment group (67.0%) compared to the SOC group (41.6%, p < 0.05). Hypertension, diabetes type II, coronary artery disease, and anemia were identified as the most common comorbidities of the Chronic venous leg ulcer (CVLU) patients included in the study. Pseudomonas, Corynebacterium, and unclassified Enterobacteriaceae were dominant in the highest number of samples. Anaerococcus, Peptoniphilus, and Finegoldia, had the highest median proportion in the samples overall. Peptoniphilus abundance decreased more in the NLFU treatment group relative to SOC; similar trends were observed for Anaerococcus and Finegoldia. Progression of mediators like TNF‐alpha, IL‐1beta, IL‐6, IL‐8, and IL‐10 as well as PF4, TGF‐beta, and fibrinogen was monitored and trends for several of the mediators were identified. Fibrinogen amounts were significantly reduced over time in the NLFU treatment group (p < 0.05). IL‐8 levels declined in wound fluid from NLFU responders as well as SOC responders. Bacterial load (total bacterial abundance) determined local parameters of ulcer inflammation. If a bioburden of ≥ 10E⁵ was found compared to < 10E⁵, levels of IL‐1beta, IL‐8, and TNF‐alpha were significantly higher. In conclusion, NLFU treatment is an effective adjuvant tool for CVLU therapy. This study demonstrates that it improves wound healing by equally inhibiting abundant levels of pro‐inflammatory cytokines as well as by reducing the overall bacterial burden.     

Union Rates and Complications of Lateral Column Lengthening Using the Interposition Plating Technique: A Radiographic and Medical Record Review

Lateral column lengthening is a common procedure for correction of pes planovalgus. A tricortical bone graft has been a standard among foot and ankle surgeons. The purpose of the present study was to compare the union rates and complications between the 2 forms of fixation for lateral column lengthening. The present study was a retrospective medical record and radiograph review of 52 patients divided into 2 equal groups, allograft (group A) and opening wedge plate (group B). The radiographic analyses compared the preoperative, postoperative and long-term measurements of cuboid abduction and talonavicular angles. The outcome measures included nonunion, hardware removal, and infection. The median follow-up duration for each group was 34.5 (range 6.3 to 89.5) months and 12.6 (range 6.5 to 56.8) months for groups A and B, respectively. Group A had 4 nonunions (15.4%) and group B had 2 nonunions (7.7%). The mean radiographic measurements of cuboid abduction and talonavicular articulation for each group improved significantly. The incidence of hardware removal was greater for group A than for group B (30.8% versus 15.4%), although the difference was not statistically significant. The median time to osseous healing for group A was 12.0 (range 8.0 to 80.0) weeks and for group B was 10.0 (range 6.0 to 36.0) weeks. The interposition plating techniques for lateral column lengthening procedures had a lower nonunion rate and incidence of hardware removal compared with the traditional use of tricortical bone grafting. The findings from the present study will aid surgeons in alternative fixation for lateral column lengthening procedures.