Isolated intracranial Rosai-Dorfman disease mimicking meningioma in a child

A 9-year-old boy presented with a 12-month history of headaches and recent grand mal seizures. Computed tomography and magnetic resonance imaging of the brain revealed an enhancing right frontal convexity lesion. The preoperative diagnosis was meningioma. However, histological examination was diagnostic of Rosai-Dorfman disease. Rosai-Dorfman disease confined to the intracranial compartment is very rare, of 34 reported cases only one presented in the first decade. Optimal treatment has not been established, but complete surgical resection alone seems effective and allows histological distinction from meningioma.     

Pin tract infection with contemporary external fixation: how much of a problem?

OBJECTIVE: To determine the incidence of pin tract infection.DESIGN Retrospective chart review. SETTING: Level 1 trauma center in an urban community. PATIENTS: A total of 285 patients with 285 fractures over a 4-year period (1997-2001). INTERVENTION: External fixation. MAIN OUTCOME MEASUREMENT: Incidence of pin tract infection. RESULTS: Of 285 fractures, 32 (11.2%) were complicated by infection. The incidence of infection according to montage was 3.9% (3/77) for ring fixators, which was significantly different (P < 0.04) from the 12.9% incidence (23/178) for unilateral fixators and the 20.0% incidence (6/30) for hybrid fixators (P = 0.004). The incidences of pin tract infection for the unilateral fixator group and the hybrid fixator group were not significantly different. CONCLUSIONS: Patients with hybrid external fixators had a similar risk of pin tract infection as patients who had unilateral fixators. The infection rate in the ring fixator group was significantly lower than the hybrid external and unilateral fixator groups.     

A novel method for single cell detection of in situ telomerase or histone H3 in combination with clonal analysis by FISH

A novel method for simultaneously detecting clonality by FISH, and presence of telomerase activity (telo+ cells) or histone H3 mRNA (H3+) in single cells from a mixed leukemic population is reported. The methods were validated using K562 cells mixed with peripheral blood granulocytes and bone marrow aspirate cells from newly diagnosed AML patients. Fifty patients with AML were analyzed for telo+ cells, while eight AML patients were analyzed for FISH-Telomerase and FISH-H3+ during remission induction therapy. Our results demonstrate that: (1). changes in the leukemic populations during therapy could be followed; (2). a favorable response to chemotherapy occurred when there was a reduction in both the cytogenetically abnormal cells along with reduction in telo+ cells within this abnormal population; (3). reduction of either telo+ cells or FISH+ cells alone did not correlate with good response. H3+ could be detected in only 4% of the leukemic population, most of which were cytogenetically abnormal. These newly established methods allow sub-populations of cells to be followed during disease progression and treatment and to elucidate factors that give a specific clone proliferative advantage.     

The use of sputum cell counts to evaluate asthma medications

Total and differential cell counts from hypertonic-induced, dithiothreitol-dispersed sputum provide reproducible measurements of airway inflammatory cell counts, which are responsive to treatment with anti-inflammatory drugs. They have helped to understand the kinetics of inflammatory cell changes in asthma after the reduction of corticosteroids and the subsequent re-introduction of treatment. They have identified that the presence of sputum eosinophilia in asthma, chronic cough and chronic airflow limitation is a predictor of steroid-responsiveness and of lack of 'asthma control'. They can be used to study the dose-response effect of inhaled corticosteroids and may be useful to establish the relative potency of different corticosteroid formulations and delivery devices. Sputum cell counts are also useful to study the potential anti-inflammatory effects of drugs like theophylline, long-acting beta-adrenoceptor agonists, leukotriene antagonists and newer drugs in development. They may be helpful to select add-on therapy to corticosteroids in 'difficult-to-control' asthma.     

Adrenomedullin decreases extracellular signal-regulated kinase activity through an increase in protein phosphatase-2A activity in mesangial cells

Adrenomedullin is a recently identified peptide hormone that has receptors in a number of different systems including renal mesangial cells. We reported recently that adrenomedullin can cause a decrease in extracellular signal-regulated kinase (ERK) activity and increase jun amino-terminal kinase (JNK) and P38 mitogen-activated protein kinase (P38 MAPK) acitivities in rat mesangial cells. Associated with these responses we also reported that adrenomedullin can decrease proliferation and increase apoptosis in mesangial cells. The major aim of the present study was to examine the mechanism of decrease in ERK activity by adrenomedullin and to identify the role of protein phosphatase 2A (PP2A) in the decrease in ERK activity, using okadaic acid [9,10-Deepithio-9,10-didehydroacanthifolicin], a selective inhibitor of PP2A at low nanomolar concentrations. The adrenomedullin-induced decrease in [3H]-thymidine incorporation and increase in apoptosis were reversed by okadaic acid at the concentration that selectively inhibits PP2A. Okadaic acid completely reversed the ERK inhibition caused by adrenomedullin, suggesting that PP2A may be involved in the adrenomedullin-mediated changes in proliferation, apoptosis and ERK activity. PP2A activity in mesangial cells was increased over time following exposure to adrenomedullin. The tyrosine phosphorylation of ERK did not change significantly following adrenomedullin treatment although the ERK activity was decreased significantly. This suggests that the decrease in ERK activity is not mediated through a decrease in MEK (a dual phosphorylating kinase upstream of ERK) or by an increase in MKP-1/2 (a dual specificity phosphatase) activities. Thus we conclude that the mechanism of adrenomedullin-induced decrease in ERK activity in rat mesangial cells is at least in part mediated by an increase in PP2A activity.     

Labeling of epsilon-lysine crosslinking sites in proteins with peptide substrates of factor XIIIa and transglutaminase.

Peptides patterned on the N-terminal sequence of fibronectin were synthesized and tested for amine acceptor qualities in reactions with dansylcadaverine catalyzed either by coagulation factor XIIIa or intracellular transglutaminase (protein-glutamine:amine gamma-glutamyltransferase, EC 2.3.2.13). On the basis of inverse half-saturations of the enzymes, the order of acceptor substrate affinity for factor XIIIa was pEAQQIV much greater than Boc-AQQIV greater than Boc-QQIV, and for transglutaminase, Boc-QQIV greater than Boc-AQQIV greater than pEAQQIV (amino acid residues are shown in one-letter code; pE, pyroglutamic acid; Boc, tert-butyloxycarbonyl). Sequence analysis of dansylcadaverine-substituted pEAQQIV indicated that the first of the two adjacent glutamine residues was the target of enzymatic modification. Boc-QIV showed no substrate activity with either enzyme. Crosslinking of crystallins in Ca2(+)-treated rabbit lens homogenate was readily inhibited by Boc-QQIV, Boc-AQQIV, and pEAQQIV, as was the formation of alpha-chain polymers in human fibrin by pEAQQIV in the presence of human factor XIIIa. SDS/PAGE analysis suggested that the inhibitory peptides selectively blocked the electron donor functionalities in these enzymatic crosslinking reactions.     

Effect of concentration and hyaluronidase on albumin diffusion across rabbit mesentery.

OBJECTIVE: To measure the diffusion coefficient of albumin through rabbit mesentery using the steady-state flux of radioactive tracer 125I-albumin. The effect of albumin concentration and testicular hyaluronidase were also studied. METHODS: Mesenteric tissue was bonded between two plates, exposing a 7 mm diameter surface, with two chambers on either side. One chamber was filled with a test solution of albumin containing the radioactive tracer and the other with lactated Ringer solution. The solutions in both chambers were stirred with small magnetic cylinders. The chamber filled with lactated Ringer solution was placed in a well-type NaI(Tl) detector, and the radiation emitted from the tracer that diffused across the mesentery was monitored continuously for 9 hours. The diffusion coefficient (D) was calculated using Fick's law of diffusion. The diffusion coefficient was measured at albumin concentration differences (delta C) between approximately 0 and 10 g/dL. The diffusion coefficient was also measured with testicular hyaluronidase at three different albumin-concentration differences. RESULTS: The diffusion coefficient increased significantly (P < 0.0001) approximately three-fold from a mean value of 2.2 x 10(-8) +/- 1.2 x 10(-8) (SD) cm2/s at 0-0.5 g/dL delta C to 5.9 x 10(-8) +/- 1.1 x 10(-8) (SD) cm2/s at 10 g/dL delta C. The values are much less than the free diffusion coefficient of albumin (6 x 10(-7) cm2/s). Testicular hyaluronidase added to the albumin solution decreased D by approximately 60%, but did not eliminate the increase in D with delta C. CONCLUSIONS: The increase in D with delta C and the reduced D with hyaluronidase were attributed to a reduced albumin-excluded volume caused by an interaction between albumin and hyaluronan. Further studies are required to define this interaction.     

Autologous stem cell transplantation following induction therapy with an anthracycline-based regimen including interferon-alpha for low-grade non-Hodgkin's lymphoma

The role of upfront autologous stem cell transplantation (ASCT) in low-grade non-Hodgkin's lymphoma (LGNHL) continues to be an area of investigation. After undergoing this novel anthracycline-based induction regimen including interferon (IFN)-alpha, a group of LGNHL patients received high-dose chemotherapy followed by ASCT. The induction regimen was based on the concept of regrowth resistance in which patients received nonmyelotoxic agents mid-cycle to slow tumor proliferation between courses of cytotoxic therapy. In addition, IFN-alpha was given at the end of the cycle because studies have shown that it has a 50% response rate in treating LGNHL. We treated 44 consecutive patients between August 1993 and February 1999 with an induction regimen containing cyclophosphamide, mitoxantrone, and teniposide intravenously on day 1 with oral prednisone given on days 1-5. On day 15, patients received vincristine and bleomycin IV. IFN-alpha-2b subcutaneously was administered on days 22-26. In this phase II single-institution study, there were 2 main patient groups. Nineteen patients received the chemotherapy induction regimen and 17 patients received chemotherapy followed by upfront ASCT. For the chemotherapy group, 58% had follicular histology and 84% had stage IV disease. For the ASCT group, 76% had follicular histology, and 71% had stage IV disease. Of the patients treated with chemotherapy, the overall response rate was 95% with 58% complete responses and 37% partial responses. Of the patients treated with chemotherapy and later ASCT, the overall response rate was 100% with 82% complete responses and 18% partial responses. In analyzing progression-free curves for these 2 groups of patients, there was evidence that the upfront autologous group fared better, log-rank test X(2)=4.6028, P < .0319.