Primary periosteal lymphoma: an unusual presentation of non-Hodgkin's lymphoma with radiographic,MR imaging,and pathologic correlation

This report describes a primary periosteal location of non-Hodgkin's lymphoma, without nodal disease, and without adjacent intramedullary disease at presentation. The clinical and imaging appearance of periosteal lymphoma simulates other neoplastic osseous surface tumors more than that of lymphoma in other locations. Consideration of this rare presentation of non-Hodgkin's lymphoma in the differential diagnosis of periosteal bone lesions can be helpful to ensure proper diagnosis and treatment.     

The ScanTrainer obstetrics and gynaecology ultrasound virtual reality training simulator: A cost model to determine the cost viability of replacing clinical training with simulation training

The aim of this study was to produce an economic cost model comparing the use of the Medaphor ScanTrainer virtual reality training simulator for obstetrics and gynaecology ultrasound to achieve basic competence, with the traditional training method. A literature search and survey of expert opinion were used to identify resources used in training. An executable model was produced in Excel. The model showed a cost saving for a clinic using the ScanTrainer of £7114 per annum. The uncertainties of the model were explored and it was found to be robust. Threshold values for the key drivers of the model were identified. Using the ScanTrainer is cost saving for clinics with at least two trainees per year to train, if it would take at least six lists to train them using the traditional training method and if a traditional training list has at least two fewer patients than a standard list.     

FAT ARMS,OBESITY AND CHOICE OF BLOOD PRESSURE CUFF SIZE IN DIABETIC PATIENTS

SUMMARY Four hundred consecutive diabetic patients had their mid-arm circumference (AC) measured and body mass index (BMI) calculated to determine the proportion of an unselected clinic group who would require a larger than standard adult blood pressure (BP) cuff and whether or not BMI could be used to predict AC and hence choice of appropriate BP cuff size. More than 75% of both men and women had an AC ≥29cm, justifying a larger than standard adult cuff for their BP measurement. When patients were classified according to their BMI, at least 80% with a BMI ≥30 and more than 70% with a BMI of 25-29 had a measured AC ≥29cm, while less than a third of patients with a BMI ≥25 had an AC ≥29cm. These results indicate that, in a diabetic clinic, most patients with a BMI ≥25 are likely to require an alternative adult BP cuff if their blood pressure is to be measured precisely.     

A cytokine receptor gene cluster in the X-Y pseudoautosomal region?

The receptors for interleukin-3 (IL-3), IL-5, and granulocyte- macrophage colony-stimulating factor (GM-CSF) are heterodimers comprised of ligand specific alpha chains and a common beta chain. The genes encoding the IL-5 receptor alpha chain and the common beta chain reside on chromosome 3 and 22 respectively, while the GM-CSF receptor alpha chain gene (CSF2RA) has been mapped to the pseudoautosomal region (PAR) of the sex chromosomes, which is a 2.6-Mb stretch of homologous sequence at the tips of the short arms within which a single obligatory recombination occurs during male meiosis. We have mapped the gene encoding the IL-3 receptor alpha chain (IL3RA) to the sex chromosomes by polymerase chain reaction (PCR) analysis of human-mouse or human- chinese hamster cell hybrids, and to Yp13.3 and Xp22.3 using fluorescence in situ hybridization. To explore the possibility that IL3RA is located within the pseudoautosomal region we screened the Centre d'Etude du Polymorphisme Humain (CEPH) pedigrees for an informative-restriction fragment-length polymorphism (RFLP) that showed male meiotic recombination. Two informative CEPH pedigrees were identified that displayed this phenomenon, confirming the psuedoautosomal location of IL3RA. Using long-range restriction mapping we have found that IL3RA maps to the same 190-kb restriction fragment as CSF2RA, suggesting that a cytokine receptor gene cluster may reside in the PAR.     

Procalcitonin (PCT) and C-reactive Protein (CRP) as severe systemic infection markers in febrile neutropenic adults

Background  

Procalcitonin (PCT) is an inflammatory marker that has been used as indicator of severe bacterial infection. We evaluated the concentrations of PCT as a marker for systemic infection compared to C-reactive protein (CRP) in patients neutropenic febrile.     

Identification of residues in the first and fourth helices of human granulocyte-macrophage colony-stimulating factor involved in biologic activity and in binding to the alpha- and beta-chains of its receptor

Residues within the first and fourth helices of human granulocyte- macrophage colony-stimulating factor (hGM-CSF) were analyzed for their role in biologic activity and interaction with the alpha- and beta- chains of the hGM-CSF receptor. Within the first helix substitution of the surface residues Glu14, Asn17, Gln20, Arg23, Arg24, and Asn27 or the buried residues Ala18, Leu25, and Leu28 did not significantly impair bioactivity or receptor binding. Substitutions at the buried residues Ala22 and Leu26 had intermediate bioactivity. However, substitutions of the surface residue Glu21 or the buried residue Ile19 reduced the relative bioactivity of the analogues to as little as 0.45% and 0.3%, respectively. Substitution of the charged surface residues of the fourth helix showed that substitution at Glu104, Lys107, and Lys111 had no significant effect on bioactivity, but substitution at Glu108 and Asp112 reduced the potency of the analogues to 34% and 7%, respectively. Receptor binding studies showed that, whereas Glu21 is the critical residue for binding to the hGM-CSF-receptor beta-chain, Asp112 is likely to be involved in binding to the GM-CSF-receptor alpha- chain. These results establish the relative contribution of residues in the first and fourth helices for GM-CSF bioactivity and receptor binding, and support a model where the fourth helix of GM-CSF interacts with the alpha-chain, and the first helix with the beta-chain of the GM- CSF receptor.     

Comparison of the effects of omapatrilat and irbesartan/hydrochlorothiazide on endothelial function and cardiac hypertrophy in the stroke-prone spontaneously hypertensive rat: sex differences

OBJECTIVE: The novel antihypertensive agent, omapatrilat, is both an inhibitor of neutral endopeptidase and angiotensin-converting enzyme. This study investigated the effects of omapatrilat in comparison with an angiotensin I-receptor antagonist/diuretic combination on blood pressure, endothelial function and cardiac hypertrophy in stroke-prone spontaneously hypertensive rats (SHRSP). METHODS: Male and female SHRSP were treated orally with omapatrilat or irbesartan plus hydrochlorothiazide (I + H) or vehicle for 8 weeks. Systolic blood pressure was measured weekly by tail-cuff. Cardiac hypertrophy was monitored by echocardiography at 8, 12 and 16 weeks of age. Endothelial function [basal nitric oxide (NO) bioavailability and stimulated NO release] was examined in carotid arteries using organ bath pharmacology and in mesenteric resistance arteries using wire myography. RESULTS: Compared with untreated controls, omapatrilat and I + H significantly attenuated hypertension [male control, 198.3 +/- 6.9 mmHg versus omapatrilat, 149.6 +/- 3.8 mmHg (F = 8.63 P < 0.0001), versus I + H, 145.6 +/- 5.1 mmHg (F = 7.38 P < 0.0001); female control, 170.3 +/-8.3 mmHg versus omapatrilat, 120.0 +/- 4.6 mmHg (F = 8.36, P < 0.0001), versus I + H, 112.2 +/- 2.9 mmHg (F = 9.08, P < 0.0001)] and left ventricular hypertrophy [male + female controls, 3.02 +/- 0.38 mg/g versus omapatrilat, 2.47 +/- 0.26 mg/g (P < 0.0001; 95% confidence interval, 0.27, 0.83), versus I + H, 2.49 +/- 0.21 mg/g (P < 0.0001; 95% confidence interval, 0.25, 0.83)]. Both treatments also significantly increased male carotid artery basal NO bioavailability relative to control [control, 0.62 +/- 0.17 g/g versus omapatrilat, 1.95 +/- 0.17 g/g (P < 0.0001; 95% confidence interval, -1.83, -0.36), versus I + H, 1.57 +/- 0.21 g/g (P < 0.026; 95% confidence interval, -1.31, -0.12)]. However, stimulated NO (EC50) was only improved in omapatrilat-treated males [controls, 0.19 +/- 0.06 micromol/l versus omapatrilat, 0.05 +/- 0.01 micromol/l (P = 0.05; 95% confidence interval, -1.16, -0.03)]. CONCLUSIONS: Omapatrilat treatment significantly reduced left ventricular hypertrophy and improved endothelial function in carotid arteries from male SHRSP by NO-dependent mechanisms. Despite equivalent antihypertensive and antihypertrophic actions, a similar improvement in endothelial function, specifically stimulated NO release, was not observed after treatment with I + H.     

NAD(P)H oxidase inhibition improves endothelial function in rat and human blood vessels

The NO/superoxide (O2-) balance is a key regulator of endothelial function. O2- levels are elevated in many forms of cardiovascular disease; therefore, decreasing O2- should improve endothelial function. To explore this hypothesis, internal mammary arteries and saphenous veins, obtained from patients undergoing coronary artery revascularization, and aortic and carotid arteries from Wistar-Kyoto and spontaneously hypertensive stroke-prone rats were incubated with O2- dismutase or NAD(P)H oxidase inhibitors. O2- levels were measured using lucigenin chemiluminescence; NO bioavailability was assessed in organ chambers; and mRNA expression of NAD(P)H oxidase components was quantified by use of a Light Cycler. In rat arteries, phenylarsine oxide, 4-(2-aminoethyl)-benzenesulfanyl fluoride, and apocynin all decreased NADH-stimulated O2- production, but only apocynin increased NO bioavailability. In human internal mammary arteries and saphenous veins, apocynin decreased NAD(P)H-stimulated O2- generation and caused vasorelaxation that was endothelium dependent and reversed on addition of the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester. In addition, it increased NO production from cultured human endothelial saphenous vein cells. Polyethylene-glycolated O2- dismutase also increased NO bioavailability in rat carotid arteries and human blood vessels, but the effects were smaller than those observed with apocynin. NADH-generated O2- and mRNA expression of p22(phox), gp91(phox), and nox-1 were comparable between the 2 strains of rat. This is the first study to demonstrate pharmacological effects of apocynin in human blood vessels. The increases in NO bioavailability shown here suggest that the NAD(P)H oxidase pathway may be a novel target for drug intervention in cardiovascular disease.     

Recombinant human interleukin-3 and granulocyte-macrophage colony- stimulating factor show common biological effects and binding characteristics on human monocytes

Two human hemopoietic growth factors involved in monocytopoiesis, interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were studied for their ability to stimulate blood monocytes and to bind to the monocyte membrane. Both cytokines maintained monocyte/macrophage numbers during long-term culture and increased cell size as compared with controls. Effects on cell numbers were present at low cytokine concentrations (6 to 20 pmol/L), whereas enhanced 3H-thymidine incorporation was observed only at higher concentrations (greater than or equal to 60 pmol/L). Autoradiographic studies showed only 1% to 3% of stimulated monocytes with nuclear grains. These results suggest that the primary mechanism for IL-3 and GM-CSF-induced maintenance of monocyte/macrophage numbers in humans is through an effect on cell survival. Surface receptors for both IL-3 and GM-CSF were studied by using 125I-labeled recombinant human (rh) cytokines and performing Scatchard analyses. Both cytokines showed curvilinear Scatchard plots, and computer analyses favored a two-site binding model. High-affinity binding data for 125I rhIL-3 (Kd 7.7 to 38.2 pmol/L; receptor number/cell 95 to 580) and for 125I rhGM-CSF (Kd 4.7 to 38.9 pmol/L; receptor number/cell 8 to 67) show similar binding affinities for the two cytokines but a lower receptor number/cell for 125I rhGM-CSF. Low-affinity binding characteristics for 125I rhIL-3 (Kd 513 to 939 pmol/L; receptor number/cell 179 to 5,274) and for 125I rhGM- CSF (Kd 576 to 1,120 pmol/L; receptor number/cell 130 to 657) show a similar pattern for the two cytokines. Specificity of 125I rhIL-3 and 125I rhGM-CSF binding to monocytes was established by the ability of the homologous cytokine to inhibit binding and the inability of a range of other cytokines to compete at 100-fold excess molar concentration. It is important, however, that binding of 125I rhIL-3 was partially inhibited by rhGM-CSF and that rhIL-3 partially inhibited binding of 125I rhGM-CSF to the monocyte membrane under conditions shown to prevent receptor internalization. The degree of inhibition varied between 25% and 80% in different experiments, and quantitative inhibition experiments showed that 1,000-fold excess concentrations of competitor failed to inhibit binding of the heterologous ligand completely. These results demonstrate that human IL-3 and GM-CSF have similar effects on growth and survival of human monocytes in vitro and suggest that these and other common biological effects may be mediated either through a common receptor or through distinct receptors associated on the monocyte membrane.     

Effect of an implantable cardioverter defibrillator with atrial detection and shock therapies on patient-perceived,health-related quality of life

Background

This study used a device (DDD implantable cardioverter defibrillator [ICD]) capable of delivering pacing and shock therapies to restore normal sinus rhythm in patients with atrial tachycardias or atrial fibrillation (AF). The purpose of this study was to assess the effect of the device on patient-perceived, health-related quality of life (QOL).

Methods

The DDD ICD was implanted in 267 patients with drug refractory, symptomatic AF from 45 centers across Europe, the United States, and Canada. Patients completed self-reported, validated QOL assessments at baseline and at 3- and 6-month follow-up visits (The Medical Outcomes Short Form 36 [SF-36] and the Symptom Checklist [SCL]).

Results

The mean age of the study group was 62 ± 12 years, and 73% of the patients were male. A total of 150 patients completed SF-36 assessments, and 138 patients completed SCL assessments at all 3 times. Baseline scores were more impaired (P < .05) on most SF-36 scales compared with norms for a general population, but were similar to a comparison group of patients with AF who were referred to tertiary care centers. The role-physical, physical functioning, vitality, mental health, and social functioning scales all improved significantly with time (all P < .04). Similarly, symptom frequency and severity (SCL) also improved significantly from baseline to 6 months (both P < .01). Shock therapy was delivered in 86 of the 150 patients (57%) with complete SF-36 evaluations. There was no evidence that receiving shocks decreased the relative improvement in QOL associated with implantation of the device.

Conclusions

In a 6-month period, QOL improves after implantation of a DDD ICD with atrial shock and pacing therapies. These improvements were not attenuated by receipt of shocks.