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.     

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.     

CD16+ monocytes in patients with cancer: spontaneous elevation and pharmacologic induction by recombinant human macrophage colony- stimulating factor

The small subset of circulating monocytes that express the maturation- associated CD16 antigen has recently been reported to be elevated in patients with bacterial sepsis. We now show that this novel CD16+ monocyte population is also spontaneously expanded in patients with cancer. We studied 14 patients with metastatic gastrointestinal carcinoma enrolled ina clinical trial of recombinant human macrophage colony-stimulating factor (rhMCSF) plus monoclonal antibody D612. We found that before any cytokine treatment, 12 of 14 patients constitutively displayed significant elevations in both the percentage and the absolute number of CD16+ monocytes, as compared with both normal subjects and ill patients with elevated monocyte counts but without malignancy. CD16+ monocytes accounted for 46% +/- 22% of total monocytes in the patients with cancer versus 5% +/- 3% for controls (P < .01). The increase was not attributable to infection or intercurrent illness and appeared to be associated with the underlying malignancy itself. A similar spontaneous elevation of CD16+ monocytes was observed in 35 of 44 additional patients diagnosed with a variety of other solid tumors. When patients with gastrointestinal carcinoma were treated with rhMCSF, there was a marked further increase in the percentage of CD16+ monocytes (to 83% +/- 11%), as well as in the absolute number of CD16+ cells and the level of CD16 antigen expression. In every case, the patients with cancer showed a greater CD16+ monocyte response than the maximal response obtained in normal volunteer subjects treated witha similar regimen of rhMCSF (n = 5, P < .001), suggesting that the presence of malignancy primed patients for enhanced responsiveness to rhMCSF. We hypothesize that spontaneous expansion of the CD16+ monocyte population may represent a novel biologic marker for a widespread and previously unsuspected host immune response to malignancy.     

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.     

Restriction of cell lysis by homologous complement: I. An analysis of membrane attack complex formation on target membranes

The hemolytic efficiency and binding of C9 to homologous and heterologous erythrocytes was evaluated by using a standardized passive sensitization procedure to prepare antigen- and antibody-coated erythrocytes (EA) and human serum for lysis. Heterologous bovine EA were readily lysed by human serum, whereas human EA were quite resistant to lysis. Human EA bound as many C8 and C9 molecules per cell as bovine EA when incubated under identical conditions, but four times as much bound C9 was required to lyse an equal number of human EA compared with bovine EA. The susceptibility of human erythrocytes did not increase when increased volumes of undiluted human serum were used although C9 binding increased to as much as 100,000 molecules per cell. Sodium dodecyl sulfate-resistant polymerized C9 (poly(C9)) was detected on both lysed ghosts and unlysed EA bearing complement proteins C1 through C9 (EAC1-9) after incubation with undiluted human serum; however, the ratio of poly(C9) to monomeric C9 was higher on unlysed cells than on ghosts. Although bovine and human EA bound equal amounts of human C9 at the end point, the rate of lysis and C9 uptake was slower on homologous cells. The rate-limiting step occurred before C9 binding and lysis because the rates of lysis and C9 binding were equal on homologous and heterologous EAC1-8 targets, but the extent of lysis of homologous cells was still lower than lysis of heterologous cells. Human erythrocytes lose restriction against homologous hemolysis during storage in autologous plasma or in isotonic buffers.     

Inhibition of proliferation and induction of apoptosis in juvenile myelomonocytic leukemic cells by the granulocyte-macrophage colony- stimulating factor analogue E21R

Juvenile myelomonocytic leukemia (JMML) is a malignancy that almost inevitably leads to death before adulthood. Chemotherapy has given disappointing results and a substantial number of patients relapse after bone marrow transplantation. A salient feature of this disease is that the JMML cells produce granulocyte-macrophage colony-stimulating factor (GM-CSF) spontaneously and survive and proliferate without exogeneous GM-CSF. Furthermore, JMML cells are hypersensitive to GM-CSF with addition of this cytokine leading to enhanced proliferation. We have recently generated a human GM-CSF analogue, E21R, that acts as a complete and selective GM-CSF receptor antagonist. We have now tested this molecule as a potential new agent to control the leukemic cell load in JMML with particular emphasis on its role in JMML cell survival. We found that E21R inhibited the spontaneous growth of JMML cells in vitro and caused their apoptosis in a dose- and time-dependent manner in seven of seven cases. In contrast, neither a neutralizing anti-GM-CSF monoclonal antibody (MoAb) nor a selective interleukin-1 (IL-1) receptor antagonist affected JMML cell survival. Furthermore, the apoptotic effect of E21R was seen even in the presence of interleukin-1 beta and tumor necrosis factor-alpha, which have also been implicated in the pathogenesis of JMML. The inhibitory effects of E21R on JMML cell growth and viability offer a novel approach to therapy in this lethal childhood leukemia.     

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.     

Precision of navigated and conventional open-wedge high tibial osteotomy in a cadaver study

High tibial osteotomy (HTO) is an established treatment option for isolated medial osteoarthritis in young and active patients. One important factor for success of this procedure is the degree of correction of the weight-bearing line. Computer-assisted navigation systems are believed to improve the precision of axis correction through intraoperative real-time monitoring. This study investigates the precision of correction of the weight-bearing line in open-wedge HTO with and without a navigation system.Nineteen legs of well-preserved human cadaver were randomly assigned to navigated (n = 10) or conventional (n = 9) HTO. In order to achieve a sufficient amount of correction in all legs the weight-bearing line was aimed at 80 percent of the width of the tibial plateau.The mean deviation of the weight-bearing line from the desired 80 percent was 1 percent in the navigated and 8.6 percent in the conventional operated legs (p = 0.002). The weight-bearing line of all navigated but only 5 of the 9 conventional operated legs was within a ± 5 percent tolerance level (p = 0.33).Navigated open-wedge HTO achieved better correction of the weight-bearing line than the conventional method in human cadaver legs. Future studies have to prove this advantage in a clinical setting and it''s effect on patient outcome.     

Analysis of the histologic features in the differential diagnosis of intrahepatic neonatal cholestasis

AIM： To compare the histologic features of the liver in intrahepatic neonatal cholestasis （IHNC） with infectious, genetic-endocrine-metabolic, and idiopathic etiologies. METHODS： Liver biopsies from 86 infants with IHNC were evaluated. The inclusion criteria consisted of jaundice beginning at 3 mo of age and a hepatic biop- sy during the 1st year of life. The following histologic features were evaluated： cholestasis, eosinophilia, giant cells, erythropoiesis, siderosis, portal fibrosis, and the presence of a septum. RESULTS： Based on the diagnosis, patients were classified into three groups： group 1 （infectious; n = 18）, group 2 （genetic-endocrine-metabolic; n = 18）, and group 3 （idiopathic; n = 50）. There were no significant differences with respect to the following variables： cholestasis, eosinophilia, giant cells, siderosis, portal fibrosis, and presence of a septum. A significant dif- ference was observed with respect to erythropoiesis, which was more severe in group 1 （Fisher＇s exact test, P = 0.016）. CONCLUSION： A significant difference was observed in IHNC of infectious etiology, in which erythropoiesis was more severe than that in genetic-endocrine-meta- bolic and idiopathic etiologies, whereas there were no significant differences among cholestasis, eosinophilia, giant cells, siderosis, portal fibrosis, and the presence of a septum.