The median age was 70 years (range 24–85) and the majority of patients (86.9%) were of performance status 1/2. The most common metastatic site was liver. In all, 84 patients were assessable for response. The overall response rate was 38% (95% CI: 27.7–49.3) and a further 33.3% of patients achieved stable disease over 12 weeks. There was good symptom resolution ranging from 64 to 86%. Grade 3/4 toxicity was as follows: hand–foot syndrome 19.7%; diarrhoea 10%; neutropenia 2.4%; infection 2.3%. Capecitabine and MMC have shown encouraging activity with a favourable toxicity profile, a convenient administration schedule, and could be considered for patients deemed unsuitable for oxaliplatin and irinotecan combinations.This study was designed to assess the safety and efficacy of capecitabine and mitomycin C (MMC) in previously untreated patients with advanced colorectal cancer (CRC). Patients received capecitabine 2500 mg m Colorectal cancer (CRC) is the second most common cancer in Europe and 500 000 patients die from the disease annually worldwide . AlthougP=0.003)  of 11 months. These results were improved by prolonged infusion of 5FU, which led to higher response rates, a different toxicity profile and a small but significant increase in OS to 12 months . A varieP=0.003) .vs 5FU/LV alone produced superior response rates and progression-free survival (PFS) for the combination arm. However, the improvement in OS was not statistically significant  or infused 5FU/LV demonstrated an improved OS compared to 5FU/LV alone  and vascular syndrome  (P<0.001)  .In the United Kingdom, the National Institute for Clinical Excellence (NICE) has issued guidance on the treatment of advanced CRC based on the currently available data. It has recommended 5FU/LV in combination with oxaliplatin as first-line treatment for patients with potentially resectable metastatic disease confined to the liver. For all other patients, first-line chemotherapy should be instituted with capecitabine monotherapy or 5FU/LV. Furthermore, a recent physician-based survey of first-line treatment for advanced CRC revealed that 30% of patients worldwide still receive fluoropyrimidine monotherapy .Mitomycin C (MMC) has been used in the treatment of CRC for many years. A randomised study of protracted venous infusion 5FU with or without MMC conducted in this setting resulted in an improved response rate, failure-free survival (FFS) and better quality of life, but no OS benefit for the combination arm , renal (creatinine clearance >30 ml min−1) and hepatic  function, WHO performance status 0–2, life expectancy of at least 3 months and no concurrent uncontrolled medical illness. Patients were excluded if there were medical or psychiatric conditions precluding informed consent, renal impairment, known malabsorption syndrome or significant cardiac disease, arrythmias or angina pectoris.The eligibility criteria were histologically confirmed advanced colorectal adenocarcinoma, no prior chemotherapy except adjuvant treatment at least 6 months previously, adequate bone marrow , was given as an intravenous bolus every 6 weeks for a total of four courses. Patients continued on treatment for 12 weeks and were then re-assessed. If there was no disease progression, treatment continued for a further 12 weeks.Capecitabine, 2500 mg m9 l−1 or the platelet count <100 × 109 l−1, capecitabine and MMC were delayed until resolution and re-initiated at full dose for 1 week delay and with a subsequent 25% dose reduction for 2 week delay.Toxicity was evaluated and graded according to the National Cancer Institute common toxicity criteria (version 2.0) . During the study, full blood count, urea and electrolytes, liver function tests and CEA were performed at weeks 3 and 6 initially, then 6 weekly thereafter.Tumour response by CT assessment was performed according to RECIST criteria at 12 and 24 weeks .A total of 92 patients were recruited between September 2001 and January 2004. Patient demographics are shown in All eligible patients commenced treatment at full dosage for a planned 24-week course. The median treatment duration was 16 weeks (range 1–24). Dose intensities of the intended starting dose of capecitabine and MMC were 82 and 78%, respectively. Treatment delays occurred in 38 (43.7%) patients.In all, 84 patients were evaluable for response at the time of analysis. Eight patients were not evaluable for response: four died prior to response assessment, one had nonmeasurable disease, one patient underwent abdominal surgery after one cycle and two patients have not yet had response assessment at 12 weeks. Response data are shown in in situ and synchronous metastases.In total, 28 patients (33.3%) achieved stable disease for a minimum of 12 weeks and 24 (28.5%) developed progressive disease. Symptomatic improvement was observed in a large proportion of patients as shown in Overall, the treatment was well tolerated and the most commonly reported events are demonstrated in Three (3.75%) patients developed red cell fragmentation and therefore discontinued MMC, but no cases of haemolytic uraemic syndrome were detected.With a median follow-up of 12.7 months, 55.4% of patients had died at the time of analysis. The median OS for this regimen was 14.3 months (95% CI 11.39–17.2) with 1 year OS of 54.8% (95% CI 41.6–66.1)  received second-line chemotherapy on disease progression . Three patients were re-challenged with capecitabine/MMC and seven with capecitabine alone; these patients demonstrated a progression-free interval of ⩾6 months after an initial response to XMMC.This trial has demonstrated that capecitabine/MMC is an effective and well-tolerated regimen for patients with untreated advanced CRC. It produced an overall response rate of 38% (95% CI 27.7–49.3), median FFS of 7.11 months (95% CI 6.13–8.10) and a median OS of 14.3 months (95% CI 11.39–17.2). Furthermore, 33.3% of patients achieved stable disease and overall the regimen produced good symptom resolution. The median OS previously reported with capecitabine alone was 12.9 months (95% CI 12.0–14.0) and FFS 4.6 months (95% CI 4.3–5.3) .et al recently compared capecitabine with the addition of oxaliplatin or irinotecan in a randomised phase II study. The ORRs for capecitabine/irinotecan and capecitabine/oxaliplatin were 37 and 49.3%, and PFS 8.2 and 6.6 months, respectively (−2 for 14 days every 21 days. At the lower dose of capecitabine (1500 mg m−2), the ORR was 37.1% (95% CI 21.5–55.1) and median PFS was 6.9 months with 20% grade 3/4 diarrhoea and one treatment-related death  has demonstrated that a significant proportion of patients treated with first-line therapy still receive fluoropyrimidine monotherapy. In the UK, this figure is particularly high (59%), which may be explained by NICE guidance. However, the corresponding figures for North America, Canada and Germany are 30, 32 and 42%, respectively . This imIn summary, this trial has demonstrated that capecitabine and MMC is an active and safe combination in untreated advanced CRC. It provides ease of administration, while avoiding the potential indwelling venous catheter-related complications, and can be given in the outpatient setting. It may be a valuable therapeutic option for those patients considered unsuitable for irinotecan and oxaliplatin. Furthermore, it offers an alternative treatment for those patients receiving fluoropyrimidine monotherapy, in which context MMC improves efficacy without incurring additional toxicity.


Currently available prognostic tools appear unable to adequately predict recurrence and progression in non muscle-invasive bladder carcinomas. We aimed to assess the prognostic value of immunohistochemical evaluation of the cell cycle markers p53, p16 and pRb. Paraffin blocks were obtained from 78 cases of pTa and pT1 transitional cell carcinomas, for which long-term follow-up was available. Representative sections were stained using antibodies against p53, p16 and pRb. Altered marker expression was found in 45, 17 and 30% of cases, respectively. Concurrent alteration of two or three markers occurred in 19% of cases, and was significantly associated with grade and stage. In univariate survival analysis, the concurrent alteration of any two markers was significantly associated with progression. The greatest risk was produced by alteration of both p53 and p16, which increased the risk of progression by 14.45 times  3.10–67.35). After adjusting for grade and stage, this risk was 7.73 (CI 1.13–52.70). The markers did not generally predict tumour recurrence, except in the 25 pT1 tumours. In these, p16 alteration was associated with a univariate risk of 2.83 (CI 1.01–7.91), and concurrent p53 and p16 alteration with a risk of 9.29 (CI 1.24–69.50). Overall, we conclude that the immunohistochemical evaluation of p53 and p16 may have independent prognostic value for disease progression, and may help guide management decisions in these tumours. The clinical course of non muscle-invasive transitional cell carcinomas of the bladder is unpredictable. Following primary resection, most patients with pTa or pT1 tumours will develop recurrences, while around 10–20% will suffer progression to potentially life-threatening muscle-invasive disease. Conventional prognostic variables such as grade and stage are unable to adequately predict which patients will suffer recurrence and progression, and this leads to difficulty in selecting the most appropriate management. The identification of a subset of patients requiring aggressive but curative management, such as cystectomy, would be a great advantage. Consequently, much attention has been focused towards the identification of prognostic markers of progression and recurrence.INK4A and RB genes, respectively  original tumour material was available and (b) satisfactory follow-up data could be obtained. No other exclusion criteria were made. The resulting cohort comprised 78 patients of whom 58 (74%) were male. The median age at diagnosis was 66 years (range 24–90), and the median duration of follow-up was 8.0 years (range 3 months–18.2 years). All haematoxylin–eosin (H&E) sections were examined by a histopathologist (DMB) to determine grade and stage according to the WHO  classifiAll patients were treated by transurethral resection with curative intent. None received intravesical BCG  for primary disease. Follow-up cystoscopies were performed on all cases initially at 3-monthly intervals, subsequently increased to 6-monthly intervals according to individual tumour characteristics. Recurrent disease was treated by transurethral resection/diathermy, with or without intravesical instillation of BCG.Definitions for recurrence and progression were set prior to analysis of the data. Specifically, recurrence was defined as the reappearance of a biopsy-proven lesion. Progression was defined as advancement in stage or dedifferentiation to grade 3 disease (μm. Immunohistochemistry was performed using a standard avidin–biotin complex (ABC) method using the Vectastain Universal ABC Elite Kit . The primary antibodies were p16 , pRb , and p53 . Sections for p16 and pRb immunohistochemistry were heated for 4 min in 0.01 M citrate buffer (pH 6.0). For p53, antigen retrieval was by overnight incubation in 0.01 M citrate buffer at 60°C. Sections were counterstained with Gill's haematoxylin.Paraffin sections were cut at 3 Negative and positive controls were included with each batch. For negative controls, duplicate sections for each case were stained by an identical method, except bovine serum albumin with azide was substituted for the primary antibody solution. Positive controls included a high-grade invasive breast carcinoma for p53, cervical intraepithelial neoplasia for p16 and normal tonsil for pRb.Immunohistochemical evaluation was carried out qualitatively, by two investigators (DMB and AWH) at a double-headed microscope, who reached consensus for the percentage of positive tumour cells in each case. Only nuclear staining was considered specific for p53 and pRb, and all reactive nuclei were considered positive irrespective of intensity. For p16, both nuclear and cytoplasmic staining were included. Evaluation was performed blind, without knowledge of patient outcome or other clinicopathological variables.Threshold percentages were applied to distinguish between normal and altered expression patterns, which were established prior to statistical analysis of the data. Specifically, p53 expression was defined as altered when at least 20% of cells showed nuclear staining . Ethical approval for this study was obtained from East London and City Health Authority Research Ethics Committee.Associations between marker alteration and grade and stage were examined using Fisher's exact test and the χFor all three antibodies, the pattern of staining was frequently heterogeneous within a given tumour, with variation in both the percentage of positive cells and the intensity of staining . No statistically significant associations existed between the markers themselves.Cases were classified as normal or altered with respect to their immunophenotype for each marker. The distribution of cases between these categories is given in Cases were then further classified according to the number of markers with altered expression patterns as (a) all expressed normally, (b) one marker altered, or (c) two or three markers altered. Normal expression of all three markers was found in 25/78 cases (32%), while 15/78 tumours (19%) showed concurrent alteration of two or three markers. This index was strongly associated with both grade and stage . Altered p53 expression closely approached significance (P=0.064), while pRb alteration was not significant (P=0.150). Cox regression was used to calculate univariate relative risks for each of these variables. The greatest risk was conferred by grade 3 disease, which was associated with a relative risk of 3.88 (95% CI 1.50–10.09) compared to G1/G2 tumours. Stage pT1 increased the risk of progression by 2.66 times (CI 1.03–6.91) compared to pTa tumours. The relative risk for progression associated with altered p53 expression was 2.48 (CI 0.92–6.74), for p16 was 2.98 (CI 1.04–8.53) and for pRb was 2.01 (CI 0.76–5.28).Progression to a more aggressive tumour phenotype occurred in 17/78 patients (21.8%) in this series. Grade 3 disease, stage pT1, and altered p16 expression were significantly associated with progression (P=0.007) compared with a normal immunophenotype. To assess the risk associated with specific combinations of marker alterations, relative risks were calculated for each of the three marker pairings. The greatest risk for progression was produced by concurrent alteration of p53 and p16 . By contrast, the risk was 1.76 (CI 0.27–11.66) for concurrent alteration to p53 and pRb, and 2.44 (CI 0.30–19.94) for p16 and pRb. G3pT1 tumours were associated with a risk for progression of 1.67 (CI 0.39–7.08) in this model.When analysis was restricted to the 53 pTa tumours, none of the individual markers achieved statistical significance for the prediction of subsequent tumour progression. The univariate risks were 2.66 (CI 0.66–10.77) in the case of p53 alteration, 3.37 (CI 0.67–16.82) for p16 alteration, and 1.83 (CI 0.44–7.69) for pRb alteration. Of note, however, was the prognostic information provided by the combined p53/p16 index. This was associated with a relative risk of 2.67 (CI 0.59–12.01) for alteration to either p53 or p16, and of 15.27 (CI 1.41–165.59) for concurrent alteration to both markers. On multivariate analysis using a model containing the p53/p16 index and grade, no variable achieved significance for independent prognostic value.The markers were not significant prognostic factors in the 25 pT1 tumours, for which the individual relative risks were 0.95 (CI 0.19–4.76) for p53 alteration, 2.34 (CI 0.55–10.03) for p16, and 1.90 (CI 0.51–7.09) for pRb. The p16/pRb index was the closest to significance in this cohort, being associated with a relative risk of 1.23 (CI 0.27–5.57) for alteration to either marker, and 5.28 (CI 0.88–31.72) for concurrent alteration to both markers.vs pTa was 1.18 (CI 0.66–2.12). Similarly, analysis of individual molecular markers revealed no significant differences in recurrence rates between the normal and altered expression patterns. The relative risk for recurrence associated with p53 alteration was 0.65 (CI 0.36–1.15), for p16 was 1.54 (CI 0.74–3.19), and for pRb was 1.39 (CI 0.77–2.53).Recurrence occurred in 50/78 patients (64.1%) in this cohort. Cox regression analysis indicated that neither grade nor stage significantly predicted recurrence. Grade 3 disease conferred a relative risk of 1.28 (CI 0.67–2.45) compared to G1/G2 tumours, while the risk associated with stage pT1 On examining the molecular markers in pairs, only the combined p53/p16 status yielded differences in recurrence rates approaching statistical significance. A single alteration to either p53 or p16 appeared protective against recurrence, conferring a relative risk of 0.56 (CI 0.31–1.00) compared with a normal immunophenotype. Concurrent alteration to both markers, however, produced a 2.81-fold increase in the risk of recurrence (CI 0.94–8.40). After adjusting for grade and stage, the risk ratios for recurrence were 0.45 (CI 0.23–0.88) for a single alteration, and 2.21 (CI 0.68–7.19) for alteration to both markers. No other marker combination was able to improve on the predictive power of this model.On confining the analysis to the 53 pTa tumours, no significant prognostic variables for recurrence were found. However, in the 25 pT1 tumours, p16 alteration was prognostic, increasing the risk of recurrence by 2.83 times (CI 1.01–7.91). Although p53 alteration was not individually associated with recurrence, the combination of p53 and p16 alteration was more informative. This index was associated with a risk ratio of 0.52 (CI 0.14–1.91) if one marker was altered, and 9.29 (CI 1.24–69.50) if both markers were altered. It was not possible to assess this risk satisfactorily against grade in multivariate analysis due to the absence of G1 tumours within this cohort. The p53/pRb and p16/pRb indices were not significant predictors of recurrence in this group.The findings of this study indicate that immunohistochemical evaluation of p53 and p16 may identify a subset of patients at high risk for progression to more aggressive disease. This may be of use in selecting patients for early aggressive therapy. In contrast, tumour recurrence is not generally predicted by these markers.TP53 mutation and p53 expression  and elevated (>50%) expression should be considered abnormal (Our findings provide further evidence for the value of phenotype-associated marker panels over single molecules in predicting progression in pTa and pT1 bladder cancers. On univariate analysis, all three markers appeared to be related to progression, but only p16 alteration was significant in this respect. p53 alteration closely approached, but did not reach, significance in this cohort. This result is similar to that of There remains a need for an improved negative prognostic tool in these tumours. In this series, however, four of the 35 cases with normal p53 and p16 expression progressed to a more aggressive phenotype. Thus, while these markers may have a role in identifying patients at high risk of progression, it would appear that they are less suitable for identifying low-risk patients.In the 53 pTa tumours, the p53/p16 combination remained the most informative predictive variable on univariate analysis, although failed to yield significant prognostic information when assessed against grade in multivariate analysis. The need for improved prognostic variables is arguably greater in pT1 tumours, and on analysis of the 25 pT1 tumours in this series the markers failed to demonstrate significant prognostic value. Nevertheless, there remained a trend towards a greater risk in tumours with concurrent alteration to two markers as opposed to those with single marker alteration, with the p16/pRb index most closely approaching significance in this respect. We speculate that in a larger cohort this trend might become significant.Escape from G1/S checkpoint control is important in malignant progression, linked with increased proliferative and decreased apoptotic capacity. Given the complexity of the molecular pathways regulating the checkpoint, it seems likely that various degrees of dysfunction could result from different combinations of molecular abnormalities. p53, p16 and pRb are key components in this checkpoint, and as such, their inactivation disrupts its normal function. By removing collateral and ‘fail-safe’ pathways, the inactivation of more than one of these molecules might be expected to increase the severity of this dysfunction. This may account for the increased predictive power apparently offered by simultaneous examination of multiple markers in relation to disease progression.In contrast, recurrence was not generally associated with the status of these markers. An interesting exception to this was in the 25 pT1 tumours, in which p16 alteration was prognostic, and further improved by combined analysis with p53. It would be unwise to draw conclusions on this from such a small cohort, however, it is an intriguing point worthy of further exploration. Other series have found the markers to be largely nonprognostic in relation to tumour recurrence (Certain limitations must be borne in mind when drawing conclusions from these data. Firstly, the evaluation of staining in this study was qualitative. However, it represents the most likely method by which such investigations would be interpreted in routine clinical practice. In this respect, it may have advantages over formal quantification methods which, although possibly less subjective, are time-consuming and would probably be impractical outside a research setting.Secondly, care must be taken in drawing comparisons with other studies. In addition to the different approaches for evaluation of staining mentioned above, differences also exist in the immunohistochemistry protocols used between laboratories. This can lead to variability in results (Thirdly, the definition used for bladder tumour progression is sometimes variable. Most studies define progression as advancement to muscle-invasive disease. However, given that grade 3 and stage pT1 tumours represent more malignant disease requiring more aggressive treatment, we set a wider definition to include progression to such phenotypes. While we believe that this definition is more applicable to clinical practice than the relatively narrow definition used elsewhere, the discrepancy must be borne in mind when comparisons are being drawn.In spite of these caveats, our findings indicate that patients with concurrent alteration to both p53 and p16 were at a significantly higher risk of disease progression than patients with a normal immunophenotype for these markers, after adjusting for grade and stage. To our knowledge, this is the first report of this effect. Moreover, we are not aware of any other study in which p53, p16 and pRb expression has been characterised in the same cohort of pTa and pT1 bladder cancers, and assessed collectively in relation to disease progression. In view of this, it is noteworthy that the concurrent alteration of p53 and p16 appeared more informative than alteration of p53 and pRb, for which prognostic value has already been established (


Anemia is considered a severe public health problem by World Health Organization when anemia prevalence is equal to or greater than 40% in the population. The purpose of this study was to determine the anemia prevalence with the associated factors in pregnant women and to determine the serum iron, folate and B12 vitamin status in anaemic pregnants in Malatya province.This is a cross-sectional survey. A multi-sage stratified probability-proportional-to-size cluster sampling methodology was used. A total of 823 pregnant women from sixty clusters were studied. Women were administered a questionnaire related with the subject and blood samples were drawn. Total blood count was performed within four hours and serum iron, folate and B12 vitamin were studied after storing sera at -20 C for six months.Anemia prevalence was 27.1% (Hb < 11.0 gr/dl). Having four or more living children (OR = 2.2), being at the third trimester (OR = 2.3) and having a low family income (OR = 1.6) were determined as the independent predictors of anemia in pregnancy. Anemia was also associated with soil eating (PICA) in the univariate analysis (p < 0.05). Of anaemic women, 50.0% had a transferrin saturation less than 10% indicating iron deficiency, 34.5% were deficient in B12 vitamin and 71.7% were deficient in folate. Most of the anemias were normocytic-normochromic (56.5%) indicating mixed anemia.In Malatya, for pregnant women anemia was a moderate public health problem. Coexisting of iron, folate and B vitamin deficiencies was observed among anaemics. To continue anemia control strategies with reasonable care and diligence was recommended. According to the United Nations (UN) estimates, approximately half of pregnant women suffer from anemia worldwide. Anemia prevalences during pregnancy differed from 18% in developed countries to 75% in South Asia . BesidesStudies well indicated the association of anemia with maternal morbidity and mortality. Worldwide, anemia contributes to 20% of all maternal deaths . Anemia Folate deficiencies since 1960s and B12 vitamin deficiencies since 1990s defined as contributing causes of nutritional anemia ,5.Since 1994, based on the recommendation of UN, experts in World Health Organization (WHO) and other agencies had developed indexes to monitor and evaluate governments' progress in reproductive health. Prevalence of anemia among pregnant women was one of the key indicators of the indexes . ReproduPrevalence studies were recomended by WHO both for monitoring the progress in reproductive health and to determine the severity of anemia since national iron supplementation program were planned according to the severity ,11.The purpose of this study was to determine the anemia prevalence with the associated factors in Malatya, and to determine the serum iron, folate and B12 vitamin status in anaemic pregnant women.The studied population was pregnant women who were resident in Malatya province located in eastern Turkey. According to the 2000 cencus total population of Malatya was 853 658. About fifteen thousand live births were reported to Health Directorate from health institutions every year and most of them (70%) were occured in urban area. According to Turkey Demographic and Health Survey-2008, 76.3% of pregnant women have received antenatal care at least once in the east Anatolia .A stratified multi-stage probability-proportional-to-size cluster sampling methodology was used in selecting the study population. This method has been used for vaccination coverage and still considered acceptable for community based prevalence studies as a fast survey method for developing countries ,14. In tPermission from the Rector of University, the Governor of Malatya and the Director of Malatya Health Directorate was taken to conduct the field survey. Data collection was performed between November 2003 and May 2004 by two teams with three persons in each team. In rural areas, selected women were visited at their homes in association with midwifes while in urban areas they were invited to the health units. After giving voluntary and informed consent, women were administered a face to face questionnaire including items about socio-demographic, fertility characteristics, diet behavior and anemia history. Questionnaire pretest was conducted on a different pregnant women group before the survey. Finally, a total of 10 ml of venous blood sample was obtained from each participant. Two ml blood was drawn into EDTA for complete blood count (CBC) and 8 ml was drawn into plain glass tubes for use in biochemical analysis.Complete blood count was achieved within four hours with Beckman-Coulter, USA. Iron, folate and B12 vitamin was studied among anaemic women after storing sera at -20°C for six months. Radio immunassay method was used to determine folic acid and vitamin B12 levels . Serum iron concentration and unsaturated iron binding capacity (UIBC) was measured using Olympus System .Cutoff values for Hb and hematocrit concentrations were selected on the basis of gestational age, using WHO criteria. The woman categorized as anaemic if the Hb < 11.0 g/dl. The frequency of the pregnant women with Hb concentrations < 10.5 g/dl at the second trimester was also presented. Manufacturer reference were used to define the normal ranges for mean corpuscular volume (MCV), 80.0-98.0 fl; mean corpuscular hemoglobin (MCH) 27.0-33.5 pg; mean corpuscular hemoglobin concentration (MCHC) 32.0-36.0 g/dL; and erythrocyte width distribution (RDW) 11.9-14.5%. Cut-off level used to indicate serum iron, folic acid and vitamin B12 deficiencies were 50 μg/dl, 3 ng/ml, and 148 pg/ml. respectively according to the literature ,16. TranData entry and statistical analysis was performed using the SPSSWIN 9.0 program. Descriptive data are presented as percentages or as means± SD. Chi-square test was performed to detect any association between anemia prevalences and independent variables. Mann-Whitney U and Kruskall Wallis tests wereused in making comparisons between the red blood cell indices. A p value of < 0.05 was considered statistically significant. Backward logistic regression analysis was performed to evaluate the independent association existing between the potential risk factors and anemia. Independent variables that were significant at the p = 0.05 level in univariate analysis were included in multivariate analysis to control for confoundings in regression models. Trimester, family income, number of live births, number of living children, family structure, PICA, receving social support were included in regression model as dichotomous variables. The results were presented in odds ratios (OR) and 95% confidence intervals. Hb < 11.0 g/dl was considered anemia for general sample while doing the statistical analysis.The average age of the pregnant women was 26.5 ± 0.2 years. The mean ages of anaemic and nonanemic women were similar, 26.9 and 26.4 years respectively (p > 0.05).Of the women, 10.2% were illeterate, 55.1% were primary school graduates. The majority were in the second trimester (63.7%) and 36.3% were in third trimester. Of the participants 33.7% were primipars. The mean number of live births was 1.3 ± 0.05 and the mean number of living children was 1.2 ± 0.05. The average monthly income was 409 ± 11.7 million Turkish Liras (about 272 $), 52.8% had a monthly income under minimum wage (303 million Turkish Liras), 12.9% had received financial support from state and 37.6% had no health insurance. The average monthly income for anemic and nonanemic women was similar (p > 0.05). A total of 29.6% of the women were living in the rural area.Table The mean values for the whole group for MCV, MCH, MCHC, RDW, Htc and Hb were 85.3 fl, 29.3 pg, 34.3 g/dl, 14.0%,33.6% and 11.5 g/dl, respectively while the values for anaemic group were 81.1 fl, 27.5 pg, 33.8 g/dl, 14.8%, 29.9% and 10.1 g/dl, respectively (p < 0.05). All haematological values were lower in anaemic group comparing with the nonanaemic group except the mean RDW value. The mean RDW (14.8%) was significantly higher among anaemic pregnants. As seen in Table Overall, the anemia prevalence was 27.1% among the studied pregnant women. Not many women had severe anemia (Hb concentration was < 7.0 g/dl in one women or < 8.0 g/dl in 3 women).The proportion of anemia was significantly higher among those women whose monthly family income was less than 500 million TL (29.1%) (p < 0.05). For the subjects who received financial support (35.8%) and lived in nuclear families (30.0%) the occurance rate of anemia was significantly higher (p < 0.05). Anemia was more frequent at the third trimester (37.5%) than at the second (21.2%) (p < 0.05). The proportion of the pregnants with a Hb concentration under 10.5 g/dl at the second trimester was 12.6%.Of the participants, 278 (33.8%) were primigravidas, 318 were nullipars (38.6%) and 230 (27.9%) were primipars. Anemia prevalences were 25.9%, 24.8% and 27.0% among them, respectively. There was no statistically significant difference between number of pregnancies and anemia prevalence (p>0.05). Anemia prevalence was highest in those with four and more live births (42.3%) and in women with four or more living children (44.1%) (p < 0.05).There was no significant relationship between the prevalence of anemia and the women' age, educational level and dietary behaviors except soil eating by univariate analysis.Of the pregnant women, 90.0% drank tea at breakfast, 40.2% consumed egg, 8.1% consumed red meat, poultry or fish and 42.0% consumed fruit and vegetables daily. Soil eating was reported by 11.2%. The percentage of soil eating was higher among illeterate (19.0%) and lower among the group who had graduated from secondary school or had higher education (5.3%) (p < 0.01). Anemia prevalence was higher among those women who ate soil (37.0%) (p < 0.05). Daily animal protein consumption frequency was 4.2% among the low-income women (< 332$), whereas it was 39.3% among high-income women (≥ 332$) (p < 0.05). Similarly, daily fruit and vegetables consumption frequency was more frequent (60.7%) among high-income and less frequent (28.6%) among low-income women (p < 0.05).Significantly associated variables in univariate analysis were put into backward stepwise logistic regression analysis to determine the independent predictors of anemia at pregnancy Table . After lPercentage distribution of micronutrient deficiencies and mean haematological values among anaemic pregnant women by some personal characteristics were presented in Table Of the anaemic women, 12.6% had UIBC level >300 μg/dl, 68.2% had TIBC level >480 μg/dl, 50.2% had a transferrin saturation less than 10.2% (data not shown) and 57.0% had serum Fe level <50 μg/L . The mean RDW value was higher among women with PICA (15.5%) and among those women who were under iron medication (15.5%). The mean value for MCV was close to the lower limit (81.1 fl) among anaemics . Among women with three children the mean value for MCV was 83.9 ± 10.1 fl and, the proportions of B12 vitamin and folate deficiencies were also higher in this category indicating the presence of mixed anemia , 56.5% had a normocytic-normochromic , 0.9% had a macrocytic (MCV > 98.0 fl) anemia and 4.5% had combined morphologic type of anemia. Iron deficiency was the most prevalent micronutrient deficiency (67.1%) among microcytic-hypochromic anemia (p < 0.05) and, folat deficiency was common in all morphologic types (p > 0.05) . Of the anaemic pregnants, 21.1% took iron supplements, 11.7% took both folate and iron supplements and, 6.3% vitamin tablets. Of the subjects with a monthly family income < 500 millionTL, 18.1% took iron supplements while 37.1% of the subjects in higher income group took iron supplements (p < 0.05). Women with no health insurance were less likely (15.7%) than the insured to receive iron supplements (p < 0.05).The study conducted in Malatya, which is an eastern Anatolian province with 800 000 inhabitants, showed a moderate prevalence of anemia (27.1%). Our findings did not correlate with the results reported by PAI and WHO which indicated that pregnant women in Turkey have had severe anemia . Our resEven though the study showed 27.1% prevalence, this is higher than the prevalences in European countries 25.1%) and in Americas (24.1%) or averaging 18% in developed countries .1% and i. TherefoAnemia prevalence in our study was also lower than those reported from different parts of the country such as 29.4% in Afyon  and 42.4Socio-economic status is a known determinant of anemia. In this study, anemia was more prevalant among those women who received financial support (p < 0.05) and who had a low monthly family income (OR = 1.6). The majority of anaemic pregnants lived in nuclear rather than extended families which might seem paradoxical. As a result of industrialization, urbanization and internal migration, people are more likely to be living in nuclear households in Turkey, recently ,21. HoweAnemia was 2.2 (OR) times more prevalent in women with four or more living children than in women with fewer children. Multiparity may induce anemia by reducing maternal iron reserves at every pregnancy and by causing blood loss at each delivery. The mean number of living children was 1.2 in our study. It was reduced to 2.4 from 2.7 between 1993 and 2003 due to the implementation of family planning services and safe motherhood programs countrywide after 1980s . EffectiThe study showed that one pregnant women out of ten was eating soil and anemia was more prevalant among soil eaters (37.0%). Soil eating (PICA) is known to be an old problem among Turkish women and it is common in many underdeveloped countries . İt is sIt was stated in the literature that tea consumption and low intake of red meat were associated with anemia -33. SomeAmong the anaemic women, half had a transferin saturation less than 10% indicating iron deficiency, one third 34.5%) were deficient in B12 vitamin and more than two third (71.7%) were deficient in folate. Pehlivanoğlu and Koç reported higher percentages of iron deficiencies among anaemic pregnant women in İstanbul; 68.5% and 62%, respectively ,41. High4.5% wereWe found that, most of the anemias were normocytic-normochromic (56.5%) and, 38.1% were microcytic-hypochromic. Despite the high propotions of folate deficiency in anaemic women, only 2 cases (0.9%) were macrocytic. It was stated in the literature that folate and B12 vitamin deficiencies caused macrocytic anemia, however concurrent presence of iron deficiency resulted in normocytic anemia .The limitations of the study should be emphasized particularly in relation with serum iron, B12 vitamin and serum folate. Fasting or nonfasting status of women was not questioned at drawning of blood samples which the results might have altered. They were studied only in anaemic women so that any comparison with non-anaemic women could not be done. Serum transferrin and red blood cell folate are better indicators of iron and folate deficiency which our budget could not afford. For the serum B12, we could comment that all forms of vitamin B12 in the serum might be detected so the deficiency was high. Also it was observed that serum B12 vitamin cutoff levels for pregnant women were not certain in the literature and being under iron medication might inluence the mean blood indices. Enfections were not questioned either.In conclusion there was a moderate anemia problem both in the second and third trimesters among pregnant women in Malatya, Turkey. The main predictors of anemia were low family income, being in the third trimester and having four or more living children. Of the anaemic women half was iron deficient, one third was B12 vitamin and two third was folate deficient. The most frequent morphologic type of anemia was normocytic-normochromic anemia and, the complete blood count suggested that anemia was caused by mixed micronutrient deficiency. Only one fifth of the anaemic women were under iron medication. Ten percent of the women were eating soil and anemia was more prevalent among soil eaters. PICA was more prevalent among low-income anaemic women, whereas consuming animal protein daily and being under iron medication were less frequent in low-income anaemic women.World health Organization recommended supplementation of all pregnant women with a daily dose of 60 mg iron and 400 g folate to control iron deficiency anemia as a primary prevention method . DisadvaThere was a moderate anemia problem in pregnant women in Malatya, Turkey (27.1%). One fourth of women enter pregnancy with anemia. Low family income (< 332$), gestational age (third trimester) and multiparity were the main predictors of anemia. The main morphologic type of anemia was normocytic-normochromic. Coexisting of iron, folate and B vitamin deficiencies was observed among anaemics. Continuing of daily iron supplementation program with folate supplementation in the beginning of pregnancy and food aid programs towards low-income women was recommended.The authors declare that they have no competing interests.LK participated in the design of the study, perfomed the data collection, performed the statistical analysis and served as the lead author of the manuscript. EP participated in the design of the study, helped to draft the manuscript. ME participated in the design of the study and helped performing the statistical analysis. CD helped to collect data. GG participated in drafting the manuscript. MEF participated in drafting the manuscript. IT carried out the immunoassays and complete blood count. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/10/329/prepub


In areas of seasonal malaria transmission, treatment of asymptomatic carriers of malaria parasites, whose parasitaemia persists at low densities throughout the dry season, could be a useful strategy for malaria control. We carried out a randomized trial to compare two drug regimens for clearance of parasitaemia in order to identify the optimum regimen for use in mass drug administration in the dry season.A two-arm open-label randomized controlled trial was conducted during the dry season in an area of distinct seasonal malaria in two villages in Gedarif State in eastern Sudan. Participants were asymptomatic adults and children aged over 6 months, with low-density P. falciparum infection detected by PCR. Participants were randomized to receive artesunate/sulfadoxine-pyrimethamine (AS+SP) combination for three days with or without a dose of primaquine (PQ) on the fourth day. Parasitaemia detected by PCR on days 3, 7 and 14 after the start of treatment and gametocytes detected by RT-PCR on days 7 and 14 were then recorded. 104 individuals who had low density parasitaemia at screening were randomized and treated during the dry season. On day 7, 8.3% were positive by PCR in the AS+SP+PQ group and 6.5% in the AS+SP group . At enrolment, 12% (12/100) were carrying gametocytes. This was reduced to 6.4% and 4.4% by day 14 (Risk difference 1.9% (95%CI −9.3% to +13.2%) in AS+SP+PQ and AS+SP groups, respectively.Addition of primaquine to artemisinin combination treatment did not improve elimination of parasitaemia and prevention of gametocyte carriage in carriers with low-density parasitaemia in the dry season.NCT00330902ClinicalTrials.gov  Plasmodium falciparum infections are asymptomatic and remain untreated. In eastern Sudan people who become infected during the wet season may retain chronic sub-microscopic asymptomatic infections throughout the dry season In malaria endemic countries of sub-Saharan Africa, the majority of Plasmodium vivax, as a prophylactic against all malaria species, and as a gametocytocidal drug against P. falciparumP. falciparum malaria to reduce transmission Artemisinin combination treatment is highly effective in eliminating asexual parasitaemia, the source of merozoites committed for gametocyte production P. falciparum infections P. falciparum parasitaemia before the transmission season in an area of marked seasonal transmission in eastern Sudan in order to identify the optimum regimen for use in mass drug administration during the dry season.Individuals with low gametocyte densities undetectable by microscopy may still be infectious to mosquitoes The protocol for this trial and supporting CONSORT checklist are available as supporting information; see The study was carried out in two villages in eastern Sudan. Abunaja Juama located at about 18 km south west of Gedarif and Kanara at 7 km south of Gedarif.P. falciparum and the main mosquito vector is Anopheles arabiensisP. falciparum. Signed informed consent forms were obtained from all participants and from the parents or guardians of children under 15 years. Exclusion criteria included pregnancy, history of allergy to sulpha drugs, fever or other signs or symptoms of illness but none of the persons screened had any of these conditions. After screening individuals were excluded if, on microscopic examination of a blood film, Plasmodium species other than falciparum were detected or the sample was negative by PCR.The whole area is characterized by seasonal malaria with transmission confined to three months of the year, October – December. The main malaria parasite is Participants were randomized to receive a standard dose of AS and SP (AS+SP) over three days, or AS+SP over the first three days plus primaquine (PQ) administered on the fourth day.P. falciparum parasitaemia, in order to identify the optimum regimen for use in mass drug administration in the dry season.We wanted to determine the efficacy of AS+SP compared to AS+SP+PQ in clearing sub-patent parasitaemia and gametocyte carriage in persons with asymptomatic sub-microscopic P.falciparum parasitaemia detected by PCR on days 3, 7 and 14 and presence of gametocytes detected by RT-PCR on days 7 and 14. For these endpoints, a sample by finger prick was obtained on days 0, 3, 7 and 14 on glass slides and on filter paper, and on days 7 and 14 venous blood was collected in K3EDTA vacutainers. Adverse events were recorded on days 1, 2, 3, 7 and 14 and packed Cell Volume was measured on days 0, 7 and 14. Parasite DNA was extracted by the Chelex-Resin method P. falciparum gametocyte specific pfS25 gene was amplified in a nested PCR to increase sensitivity of the detection The outcomes were In a previous trial 3EDTA vacutainer tubes (Becton Dickinson) for gametocyte detection by RT-PCR, and a drop of blood was collected on a glass slide for microscopic diagnosis and another drop on filter paper for PCR.A cross sectional survey was carried out in the middle of the dry season (June) 2004 to identify sub-patent parasite carriers. A finger prick sample was collected on a glass slide for microscopic diagnosis and on filter paper for molecular analysis. Persons who were positive by PCR in June and eligible were enrolled in the study and randomly allocated into one of the two treatment arms. The list of carriers was sorted according to village and age to ensure that the treatment groups were balanced with respect to these two variables. The random allocation of this ordered list into the treatment arms was then created using restricted randomization with a block size of 12 in Stata version 7 . In August, a clinical examination was performed; no participants were excluded due to illness or other exclusion criteria. Before administering the first treatment dose (day 0), a venous blood sample was obtained from each individual in KTreatment was administered under medical supervision. SP was administered on day 0 as 25 mg/kg sulfadoxine/1.25 mg/kg pyrimethamine for children under 50 kg, while adults and children weighing 50 kg or more were given three tablets (each tablet contained 500 mg of sulfadoxine and 25 mg of pyrimethamine). Artesunate was given on days 0, 1 and 2 at a dose of 200 mg (two tablets at 100 mg) for adults and for children weighing 50 kg or more, while children under 50 kg received 4 mg/kg body weight. Participants randomized to receive primaquine were, in addition, given a single dose of 0.75-mg/kg body weight on day 3. After each treatment dose, patients were observed for one hour, if the drug was vomited during the first half hour a full dose was repeated, if vomiting occurred after one hour half a dose was repeated.The trial was not blinded; however laboratory staff performing the PCR assays were unaware of the treatment allocation.95% confidence intervals were calculated for the difference between the proportions with parasitaemia and gametocytaemia in the two groups on days 7 and 14, using the modified score method of Newcombe . 114/615 (19%) had PCR detectable P. falciparum parasitaemia (including the 9 which were positive by microscopy) and were therefore eligible for enrolment into the trial. The three who were positive by microscopy for other Plasmodium species were PCR negative for falciparum.Out of a total of 615 asymptomatic individuals screened by microscopy in June 2004 (the dry season) 12 were positive for malaria parasites  when 104 eligible participants were enrolled and 10 were absent. Of these 4 (4.2%) were positive for asymptomatic th to 20th August, and followed up until 3rd September 2004.Participants were enrolled from 17The demographic data for the study group is shown in Four (4%) individuals from those who were randomized in the AS+SP group were found to be negative by PCR on day 0. Of these 3 were lost to follow up on day 14 and one withdrew consent by day 3. They have been excluded from the analysis of safety and efficacy. The remaining withdrawn and lost to follow-up cases were also excluded. Data analysis was performed according to the protocol.P. falciparum infection. However, only 20 (20.4%) out of 98 participants seen on day 3 post-treatment were found to harbour P. falciparum infection detectable by PCR. On day 7 only seven (7.4%) out of 94 participants retained PCR detectable P. falciparum infection, 4/48 (8.3%) in the AS+SP+PQ group and 3/46 (6.5%) in the AS+SP group . Similarly, five out of 92 seen on day 14 had PCR detectable parasitaemia (On recruitment (day 0) 100 (96%) out of 104 individuals carried asymptomatic sub-patent sitaemia .With regard to gametocytes, on enrolment, twelve (12%) out of 100 individuals carried gametocytes detectable by RT-PCR. None of them were gametocyte positive on day 7 or day 14. The same persons who were detected positive by PCR on days 7 and 14 were also positive for gametocytes by RT-PCR. On day 7, four (8.3%) out of 48 on AS+SP+PQ and three (6.5%) out of 46 individuals in AS+SP were found to have RT-PCR detected gametocytes . Similarly on day 14, 6.4% in AS+SP+PQ and 4.4% in AS+SP had sub-microscopy gametocytaemia (risk difference 1.9% (95%CI −9.3% to +13.2%).Two out of the seven gametocyte carriers detected on day 7 retained their gametocyte producing infection until day 14. However, gametocytes reappeared on day 14 among three individuals who were gametocyte negative on day 7.Packed cell volume was similar in both groups on day 7, mean 34.6% (15–44%) in the AS+SP group and 34.2% (26–42%) in the AS+SP+PQ group, difference between groups adjusted for baseline 0.78  P = 0.315. Similar results were seen on day 14 .No serious or severe adverse events were reported. Four of the participants (3.8%) vomited after the first treatment dose of AS+SP; 1 on AS+SP and 3 on AS+SP+PQ arm. One of these vomited immediately, refused to take the drug again and withdrew consent. The other three cases (2.9%) vomited after more than eight hours after taking the drug and the dose was therefore, not repeated for them. Two people complained of insomnia and another two complained of itching.P. falciparum parasitaemia that persist in the dry season, as a potential control strategy in areas of seasonal transmission. After treatment with AS+SP alone 80% (78/98) of subjects with asymptomatic sub-patent P. falciparum infections became PCR negative by day 3 (before administration of PQ). However, only three (6.4%) in AS+SP and four (8.3%) in AS+SP+PQ group had sub-patent gametocytes on day 7, and two (4.4%) and three (6.4%) on day 14, respectively.We compared the efficacy of AS+SP and AS+SP+PQ in clearing asymptomatic sub-patent P. falciparum was found to be less than 1∶10 P. falciparum gametocyte carriers in nature usually harbour less than 100 gametocyte µl−1 blood and there is evidence that 1–10 gametocytes µl−1 blood are infectious to mosquitoes P. falciparum to Anopheles mosquitoes P. falciparum infection to infectivity of Anopheles mosquitoes The present results are consistent with previous findings that asymptomatic sub-patent parasitaemia PfS25 gene, which is exclusively expressed by mature gametocytes Our results show the efficacy of artesunate against asymptomatic sub-patent gametocyte carriage. Gametocytes present before treatment were most probably mature since we used the P.falciparum parasitaemia in the dry season without the need for the addition of primaquine. These results, for infections near the limit of detection, may not apply to higher density infections where detectable gametocytes may persist for several weeks in spite of effective treatment of asexual parasitemia The clearance of sub-patent parasitaemia and gametocyte carriage by day 7 after treatment with AS+SP indicates that this may be an effective treatment for use to clear low density The combination AS+SP without primaquine is effective in eliminating the dry season sub-microscopic parasitaemia and gametocyte carriage. Therefore, this regimen could be recommended for use in mass drug administration in the dry season to control malaria in areas of seasonal transmission.However, it may be necessary to complete the drug administration before the rainy season and resurgence of the mosquitoes so as to avoid transmission of mature gametocytes.Protocol S1Trial Protocol(0.16 MB DOC)Click here for additional data file.Checklist S1CONSORT Checklist(0.04 MB DOC)Click here for additional data file.


The objective of this study was to calculate central motor conduction time (CMCT) of median and ulnar nerves in normal volunteers. Conduction time across the lower part of the brachial plexus was measured by using magnetic stimulation over the motor cortex and brachial plexus and recording the evoked response in hand muscles.This descriptive study was done on 112 upper limbs of healthy volunteers. Forty-six limbs belonging to men and sixty-six belonging to women were studied by magnetic stimulation of both motor cortex and brachial plexus and recording the evoked response in thenar and hypothenar muscles. Stimulation of the motor cortex gives rise to absolute latency of each nerve whereas stimulation of the brachial plexus results in peripheral conduction time. The difference between these two values was considered the central motor conduction time (CMCT).In summary the result are as follows; Cortex-thenar latency = 21.4 ms (SD = 1.7), CMCT-thenar = 9.6 ms (SD = 1.9), Cortex-hypothenar latency = 21.3 ms (SD = 1.8), CMCT-hypothenar = 9.4 ms (SD = 1.8).These findings showed that there is no meaningful difference between two genders. CMCT calculated by this method is a little longer than that obtained by electrical stimulation that is due to the more distally placed second stimulation. We recommend magnetic stimulation as the method of choice to calculate CMCT and its use for lower brachial plexus conduction time. This method could serve as a diagnostic tool for diagnosis of lower plexus entrapment and injuries especially in early stages. Magnetic motor stimulation is useful in the evaluation of a wide spectrum of nervous system disorders including multiple sclerosis, spinal cord lesions, motor neuron diseases, stroke, cervical spondylosis, intraoperative monitoring, epilepsy, pelvic floor disorders, movement disorders and some investigative conditions such as brain mapping studies -4.1,2 Specificity of the site for magnetic stimulation is not as critical as it is for electrical stimulation [Technical advances in this method occurred during the 1980s and this method has gained approval for clinical applications involving diagnostic and prognostic issues ,6. Diffemulation .One of the challenging topics in electrodiagnostic medicine is the diagnosis of proximal brachial plexus entrapment syndromes such as neurogenic thoracic outlet syndrome, especially in the early stages, when there is no significant axonal degeneration. At this stage there is only demyelination and/or a focal conduction block involving a short segment of plexus that can't be evaluated by routine peripheral nerve conduction studies and has no needle EMG findings. In this setting, use of Central motor conduction time (CMCT) can be a potentially useful technique to confirm the clinical diagnosis. Central motor conduction time (CMCT) is obtained when the peripheral conduction time (PCT) is subtracted from the absolute latency of cortex to target muscle conduction time. PCT is obtained by different methods including; F-wave latency, magnetic or electrical nerve root stimulation and stimulation of the brachial plexus ,8,9. CMCThis study was performed in the electrodiagnostic medicine clinic of Shohada Tajrish Medical Center Tehran, Iran, between May 2006 and December 2006. Overall 112 upper limbs (66 persons) were tested, with 66 limbs belonging to healthy females and 46 belonging to healthy male volunteers. They had no history of convulsive disorders. Their neurologic clinical evaluation was normal and they had no signs of neuromuscular disorders. The medical ethics committee of Shahid Beheshti Medical University, Physical Medicine and Rehabilitation Branch approved our study. After explanation of the procedure, the volunteers signed an informed consent that was written in their native language (Persian). They were also asked if they had cardiac pacemakers, implanted metallic devices or intracranial metallic clips from neurosurgical operations. Cases having one or more of these criteria were excluded from the study. If the limb temperature was below 32°C their limbs were warmed up. All the volunteers who have undergone nerve conduction studies on upper and lower limbs and cases suspected of having neuropathies were excluded. After giving thorough explanations about the process of study the volunteers were deliberately included in the study. To obtain the absolute latencies of median and ulnar nerves, the magnetic coil stimulator was placed on the motor cortex 7 cm lateral to Cz (a line connecting both tragi together)  for cortical stimulation and 70–80% of its maximal output for brachial plexus stimulation. The coil used was circular in shape with an internal diameter of 7.5 cm and its central point was used to stimulate the above mentioned targets. The recording instrument was a four channel "Toennis Neuroscreen Plus" set on: time division 5 ms, sensitivity 500–1000 μv/div. Recording electrodes were conventional bar electrodes.Data obtained in this study was analyzed by SPSS-9 software. The mean age of males was 44.7 years (range: 24–65 yrs) and that of females was 42.0 yrs (range: 18–67 yrs). The mean for the absolute latency (cortex to muscle) of the median nerve with recording from the thenar muscles was 21.4 (SD = 1.7) ms. This value was 21.9 (SD = 1.4) ms in males and 21.0 (SD = 1.7) ms in females.The mean for the absolute latency of the ulnar nerve with recording from the hypothenar muscles was 21.3 (SD = 1.6) ms. This value was 21.9 (SD = 1.5) ms in males and 20.9 (SD = 1.7) ms in females. The mean for the central motor conduction time (CMCT) of the median nerve with recording from the thenar muscles was 9.6 (SD = 1.9) ms. This value was 9.6 (SD = 2.0) ms in males and 9.6 (SD = 1.8) ms in females. The mean for the central motor conduction time (CMCT) of the ulnar nerve with recording from the hypothanar muscles was 9.4 (SD = 1.8) ms. This value was 9.2 (SD = 1.9) ms in males and 9.7 (SD = 1.7) ms in females (Table The number of cases entered in this study is remarkably larger than those used in similar studies. Zwarts in his study with a sample size of 36 obtained these results: latency of cortex to APB muscle = 20.6 ms (SD = 1.2) and CMCT recorded from APB = 7.4 ms (SD = 0.9) .In Eisen's study with a sample size of 90, he obtained these normal values: absolute latency from cortex to thenar muscles = 20.4 ± 1.5 16.8 – 23.8) and CMCT with thenar recording = 6.7 ± 1.2 (4.9 – 8.8) . We made – 23.8 a


The percentage of hypertrophic cardiomyopathy (HCM) patients who are in high risk for Sudden Death (SD) constitutes only a minority of all HCM population but the incidence of SD in this subset is high . The identification of this small but important proportion of high risk HCM patients has been the clue in the clinical evaluation of these patients.Our study cohort consisted from 123 patients with HCM who are currently followed up in our Institution. Five clinical risk factors were assessed: a family history of premature SD, unexplained syncope, Non Sustained Ventricular Tachycardia (NSVT) on 24-h ECG monitoring, Abnormal Blood Pressure Response (ABPR) during upright exercise testing and Maximum left ventricular Wall Thickness (MWT) ≥30 mm. The purpose of our study was the identification of high risk HCM patients coming from Northern Greece.Fifteen patients (12.2%) of the whole cohort had MWT ≥ 30 mm, 30 patients (24.4%) had an ABPR to exercise, 17 patients (13.8%) had episodes of NSVT in 24-h Holter monitoring, 17 patients (13.8%) suffered from syncope, and 8 patients (6.5%) had a positive family history of premature SD. Data analysis revealed that 74 patients (60.1%) had none risk factor. Twenty four patients (19.5%) had 1 risk factor, 17 patients (13.8%) had 2 risk factors, 4 patients (3.25%) had 3 risk factors, and 4 patients (3.25%) had 4 risk factors, while none patient had 5 risk factors. Twenty five patients (20.3%) had 2 or more risk factors.This study for the first time confirms that, although a 60% of patients with HCM coming from a regional Greek population are in low risk for SD, a substantial proportion  carries a high risk for SD justifying prophylactic therapy with amiodaron or ICD implantation. Hypertrophic Cardiomyopathy (HCM) is a genetically transmitted cardiac disease characterized by myocardial hypertrophy in the absence of any other cause capable of producing the magnitude of hypertrophy present . The incHighest risk for SD in HCM has been associated with any of the following noninvasive clinical markers ,6,7,9-11The study cohort consisted from 123 patients with HCM who are currently followed up in our Institution, and who completed all noninvasive clinical tests for risk stratification, ie, personal and family history, clinical evaluation, 12-lead ECG, transthoracic echocardiography, 24-h ECG monitoring, and symptom-limited upright exercise test. Patients with documented sustained ventricular tachycardia or out-of-hospital cardiac arrest and those who were on amiodarone at first evaluation were excluded. Patients' follow up commenced the time the first diagnosis was made even if the diagnosis preceded baseline patient evaluation in our clinic. The diagnosis of HCM was based on the echocardiographic appearance of left ventricular MWT greater or equal than 15 mm, in the absence of any other cause capable of producing such hypertrophy . HCM wasEchocardiographic studies were performed using a GE Vingmed Vivid 7 system . Echocardiographic examination included M-mode, two-dimensional, pulsed- and continuous-wave Doppler echocardiography, and Tissue Doppler Imaging since the time it was available in our clinic. Segmental left ventricular hypertrophy was measured in two-dimensional echocardiography parasternal short axis views according to previous described methods . StandarPatients underwent symptom-limited upright exercise test using the Bruce protocol in a Schiller AT-6C Stress Test Treadmill System. Blood pressure was measured using a mercury sphygmomanometer and auscultation of the Korotkoff sounds over the brachial artery at rest, every minute during exercise and for the first 3 min of recoveryAll patients underwent-24 h ECG monitoring  while performing ordinary daily activities.A history of syncope was defined as one or more episodes of unexplained loss of consciousness preceding patients' first visit to our Hospital.A family history of premature SD was defined as SD in one or more first-degree relatives <50 years old.NSVT was defined as a run of three or more consecutive ventricular beats at a rate of ≥120 beats/min, lasting <30 s.An ABPR was defined as a failure of systolic blood pressure to rise more than 20 mmHg, or a fall of systolic blood pressure, during exercise.Five clinical risk factors were assessed: a family history of premature SD, unexplained syncope, NSVT on 24-h ECG monitoring, ABPR during upright exercise testing and left ventricular MWT ≥30 mm.Normality plots were tested using Kolmogorov-Smirnoff test for a p value > 0.05. Distributions of variables in the study cohort are summarized as means ± SD and as medians (IQR) for non-normally distributed data. Percentages are also reported. Most of the statistical estimates were performed using the Statistical Package for Social Sciences version 17.0 .Demographic and clinical characteristics of the 123 patients are outlined in Table The mean value of LV end-diastolic diameter was 4.32 ± 0.79 cm (range 2.77 to 7.05 cm), and the mean value of LV Ejection Fraction was 71.7 ± 13% (30 to 90%). The mean value of MWT was 2.16 ± 0.57 cm (range 1.42 to 3.87 cm) and the mean value of left atrial size was 4.09 ± 0.68 cm (range 2.24 to 5.90 cm). Twenty seven patients (21.9%) had resting subaortic gradient ≥30 mmHg (range 32 to 230 mmHg). Fifteen patients (12.2%) had maximum wall thickness ≥30 mm. The above data are outlined in Table Sixty five percent of our patients were on medication at the initial or started after that. The patients mainly received b-blockers (47.9%). Amiodaron was started after first evaluation in our Institution. Thirty five percent were not on any medication. The above data are outlined in Table Fifteen patients 12.2%) of the whole cohort had MWT ≥ 30 mm, 30 patients (24.4%) had an ABPR to exercise, 17 patients (13.8%) had episodes of NSVT in 24-h Holter monitoring, 17 patients (13.8%) suffered from syncope, and 8 patients (6.5%) had a positive family history of premature SD. Data analysis revealed that 74 patients (60.1%) had none risk factor. Twenty four patients (19.5%) had 1 risk factor, 17 patients (13.8%) had 2 risk factors, 4 patients (3.25%) had 3 risk factors, and 4 patients (3.25%) had 4 risk factors, while none patient had 5 risk factors. Twenty five patients (20.3%) had 2 or more risk factors . All patients were alive at the end of follow-up. An implantable cardioverter-defibrillator (ICD) was implanted in 10 patients for primary prevention of SD. Among these patients, 3 had 4 risk factors, 2 had 3 risk factors, 4 patients had 2 risk factors, and 1 patient had 1 risk factor. The mean follow-up period after ICD implantation, was 18.6 ± 17.5 months (1 to 48 months). Defibrillator was activated appropriately in 2 patients, by providing antitachycardia pacing for sustained ventricular tachycardia, with the restoration of sinus rhythm . The annual incidence of appropriate discharges was 10.7%. One patient had an episode of inappropriate discharge (due to sinus tachycardia). Stored data were reviewed after all discharges.It is well established that in HCM-patients with a history of sustained ventricular tachycardia or documented cardiac arrest the risk of SD is sufficiently high to warrant prophylactic therapy, irrespective of the presence of other risk factors ,16 Figu. Risk stAbout half of our patients were referred from other centres for evaluation and treatment, and the other half was firstly diagnosed and evaluated in our clinic. As a consequence of this process, our study does not incorporate a substantial degree of patient selection bias. Our data indicates that a 60% of patients had no risk factors . A highThis study for the first time confirms that, although a 60% of patients with HCM coming from a regional Greek population are in low risk for SD, a substantial proportion  carries a high risk for SD justifying prophylactic therapy with amiodaron or ICD implantation.The authors declare that they have no competing interests.GKE, CP, GG and EDP conceived the original paper, collected the data, reviewed literature and wrote the manuscript. SH, IHS and GP revised the article for important intellectual content and edited the final version. GKE, DP and CK performed the ultrasounds and participated in the analysis and interpretation of data. SG and VK performed the exercise tests and participated in the interpretation of data. All authors read and approved the final manuscript.


The administration of compounds R1 and R2 at the dose level of 20 mg/kg. b. wt. siignificantly reduced the weights of testes and epididymides. Auxiliary glands showed a significant reduction after the treatment of compound R1 only. Treated animals showed a notable depression of spermatogenesis. The preleptotene spermatocytes were decreased by 76.19 and 47.06; the secondary spermatocytes by 87.4% and 54.87337; and the step-19 spermatids by 72.9 and 46.77% respectively, following the compound R1 and R2 treatment. Reduced sperm count and motility resulted in 100% negative fertility in both the treated groups. A significant fall in the content of various biochemical parameters of eproductive tissues was observed after R1 and R2 treatment in comparison to controls.The antifertility activity of organoantimony(III) complexes PhSb[RC(NC


Compounds were assayed in concentrations of 10 and 100 μM. In case of leptophos-oxon inhibited AChE, the best reactivation potency was achieved with methoxime, trimedoxime, obidoxime and oxime K027. The most potent reactivators of inhibited BChE were K033, obidoxime, K117, bis-3-PA, K075, K074 and K127. The reactivation efficacy of tested oximes was lower in case of leptophos-oxon inhibited BChE.We have evaluated  Organophosphorus pesticides  and nerve agents  are highly toxic compounds for living organisms due to their ability to inhibit the enzymes acetylcholinesterase AChE; EC 3.1.1.7) and butyrylcholinesterase . Irreversible inhibition of AChE can result in cholinergic crisis and possible death of an intoxicated organism ,3. The e.1.1.7 anA relatively new approach for prophylaxis against such intoxication is the administration of a suitable scavenger capable of neutralizing organophosphates rapidly after their penetration into the bloodstream of the organism . For thein vitro potency of 23 structurally different reactivators to reactivate human erythrocyte AChE and plasma BChE inhibited by racemic leptophos-oxon . The reactivation of BChE was tested in order to recommend suitable reactivators for preparation of pseudocatalytic scavengers. Leptophosoxon used in our experiments is a toxic metabolite of the pesticide leptophos, which is a weak AChE inhibitor itself. Racemic leptophos was previously employed to control insects in rice paddy fields and has been banned since 1978, after it was found to be highly neurotoxic to mammals [50 for horse serum BChe were found between the (−)-leptophos and (±)-leptophos forms, the IC50 of the (+)-leptophos form was four times lower. Conversely, when leptophos-inhibited housefly head AChE was utilized, there was no significant difference in IC50 between the (+)-leptophos and (±)-leptophos forms, but the IC50 of the (−)-leptophos form was approximately two times higher [In this study, we have evaluated the  mammals ,11. It hOximes were assayed in concentrations of 10 and 100 μM, which are regularly attainable in plasma during antidotal treatment of pesticide intoxication . Becausen-butanol-acetic acid-water = 5:1:2; detection by Dragendorff reagent) and NMR . Racemic leptophos-oxon  of 95% purity was purchased from Dr. Ehrenstorfer . All other chemicals used in this study were of analytical purity and were purchased from Sigma-Aldrich (Czech Republic). The reactivation activity of synthesized reactivators was tested using our in vitro reactivation test [Cholinesterase reactivators used in this study were synthesized in our lab or purchased from Leciva (Czech Republic), Merck (Germany) and Phoenix Chemicals Ltd. (United Kingdom). Purity of all the AChE reactivators utilized was tested using TLC  in order to avoid the excess of leptophos-oxon. The IC95 value was determined in a concentration range 10−3–10−9 M using experimental conditions  identical to those used for the cholinesterase inhibition (described below). Identical reaction conditions were utilized for a determination of half- life (T1/2) of reaction between the enzyme and leptophos-oxon. The concentration of an inhibitor was 5 × 10−6 M and the AChE or BChE activities were measured in 5 min intervals. The time of enzyme inhibition used in the reactivation test was equivalent to 7 × T1/2 (120 min for AChE and 45 min for BChE). The inhibition of cholinesterase was started in plastic cuvette by the addition of inhibitor solution in isopropanol to the mixture of the 0.05 M phosphate buffer (pH 7.4) and hemolyzate (activity before inhibition was set to 10 U/L) or plasma (activity was set to 13.3 U/L). The concentration of isopropanol in the sample was 5% and had no significant influence on the activity of both cholinesterases. Control samples with an uninhibited enzyme were incubated for the appropriate time with isopropanol in final concentration 5%. Then the inhibited enzyme was incubated for 10 min with a solution of the reactivator in 0.05 M phosphate buffer (pH 7.4) at concentrations of 10 μM and 100 μM. The activity of AChE (BChE) was measured spectrophotometrically by the method modified according to Ellman with acetylthiocholine (butyrylthiocholine) as a substrate [Human erythrocyte hemolyzate was used as a source of AChE and human plasma as a source of BChE. Blood samples were collected from healthy volunteers into 3.8% sodium citrate (the ratio of blood/citrate was 1:10 w/w), centrifuged for 20 min at 2,856 g and the plasma removed as supernatant was stored at −80 °C (source of BChE). Erythrocytes were washed three times with the 0.1 M phosphate buffer , hemolyzed in the 0.01 M phosphate buffer (pH 7.4) in a ratio 1:10 (w/w) and frozen at −80 °C (source of AChE). The enzymes were inhibited to 5% of their original activity using concentration corresponding to IC0 is activity of intact enzyme, ai is activity of inhibited enzyme and ar is activity of reactivated enzyme minus oximolysis.where%R is percent of reactivation, awww.graphpad.com). All experiments were carried out in compliance with the current applicable laws of Czech Republic.Each measurement was repeated three times and was conducted at standard laboratory temperature (25 °C). All data are expressed as means with corresponding SD. Groups of data were compared using the one-way ANOVA test followed by the Tukey test. Calculations were performed using software GraphPad Prism version 4.00 for Windows  of reactivation percentage values in comparisons of series of compounds denote that measured potency is significantly lower than value measured for preceding oxime at P < 0.001 level.Measured values of reactivation potency of tested compounds are summarized in a), trimedoxime (26.4%b), K027 (16.4%c), K075 (14.2%c), K074 (12.6%c) and HI-6 (11.6%c). Other assayed oximes had reactivation potency below 10% at this concentration.The data showed that the reactivation potencies for AChE inhibited by leptophos-oxon at lower concentration of oximes (10 μM) decreased as follows: obidoxime (31.4%a), followed by trimedoxime (51.3%a), obidoxime (50.3%a), K027 (49.3%a), K075 (33.8%b), HI-6 (32.8%b), K203 (30.8%b), K074 (28.1%b) and K048 (26.1%b). Reactivation efficacy of other compounds was below 25%.Different values were obtained, however, when a higher concentration of reactivators (100 μM) was used. At this concentration the best reactivation potency was achieved for methoxime  had relatively low potency. Out of the monoquaternary compounds tested, the most efficacious was pralidoxime (13.2% at 100 μM) with an aldoxime group in position 2, while other tested oximes were practically inactive . From commercially available AChE reactivators, methoxime, trimedoxime, obidoxime and oxime HI- 6 were sufficiently effective.Comparison of this data with the data from out previous study focused on the reactivation of AChE–inhibited by paraoxon shows, that obidoxime (96.9% of reactivation), trimedoxime (86.0%)  and compa), followed by oximes K033 (4.2%a), bis-3-PA (2.7%a) and K117 (2.7%a) when lower concentration of the reactivators was used, while the other assayed oximes had reactivation potency below 2.5% at this concentration.The results obtained with the BChE showed that for this enzyme the best reactivation potency was achieved for obidoxime (6.5%a), followed by obidoxime (14.3%a), K117 (13.9%a), bis-3-PA (13.1%a), K075 (12.4%a), K074 (11.5%a), K127 (11.0%a) and K269 (10.7%a). The reactivation efficacy of other compounds was below 10%.Similarly to the results obtained with AChE, different reactivation potencies were measured when higher a concentration of the reactivators was tested. Under these conditions, the reactivation ability of tested compounds decreased as follows: K033 , trimedoxime (12.2%), compound K269 (10.6%) and K075 (10.3%) were the most effective reactivators at the concentration of 100 μM [P < 0.001) is that BChE lacks the reactivator aromatic binding pocket found in AChE, which itself is a part of the AChE peripheral anionic site. This difference finally renders the current AChE reactivators, when used with BChE, non-functional [The likely reason for the significantly lower BChE reactivation ability at a higher concentration in comparison with AChE (nctional ,15. OverAccording to our results, human erythrocyte AChE inhibited by leptophos-oxon possesses very good ability for reactivation. Therefore, commercially available reactivators, commonly used in the therapy of OP intoxications, could provide sufficient efficacy in the treatment of poisonings. However, results obtained with BChE clearly showed, that none of the tested re-activators exhibited sufficient reactivation potency needed for the construction of a pseudocatalytic scavenger and therefore new compounds for this purpose need to be developed.


Current screening tests for gestational diabetes mellitus (GDM) are inconvenient. Therefore, alternative screening tests for GDM are desirable. The use of glycohemoglobin A1c (HbA1c) in screening for GDM remains controversial.We undertook this study to evaluate the utility of HbA1c in screening for GDM.Retrospective study in a tertiary teaching hospital.Laboratory records were reviewed to identify pregnant women who underwent both oral glucose tolerance test (OGTT) and HbA1c measurements over a 16-months period. The association of OGTT with HbA1c was evaluated.Data were collected using SPSS software. Comparisons of the means and calculations of sensitivities were performed.P< 0.006). At an arbitrary cut-off value of 6.0% , HbA1c would have picked up 87.1% of patients with GDM.Of 145 eligible patients, 124 had GDM and 21 patients did not, per OGTT. The percentages of patients with HbA1c values (reference range of 4.8%–6.0%) equal to or above sequential cut-point values of 5.0%, 5.5%, 6.0%, 6.5% and 7.0%  were 100%, 98.4%, 87.1%, 62.9% and 39.5%, respectively. The mean HbA1c of the patients with GDM was 6.9 + 0.8% compared to 6.4 + 0.6% for those without GDM (This study suggests that HbA1c is a reasonably sensitive screening measure of GDM in this high-risk population. Acknowledging limitations resulting from the study design, further prospective studies are warranted to verify this conclusion, and to evaluate the specificity of HbA1c as a screening test for GDM. GDM is defined as glucose intolerance with onset or first recognition during pregnancy.2 Screeni46The OGTT is regarded as inconvenient and requires fasting, warranting the search for more convenient screening alternatives. Utilizing glycohemoglobin A1c (HbA1c) in GDM screening is controversial.–12 We unThis retrospective study was performed at King Fahd Armed Forces Teaching Hospital (KFAFH) in Jeddah, Saudi Arabia, and was approved by the KFAFH Research Ethics Committee. KFAFH is a tertiary teaching military hospital serving the military personnel and the civilian employees of the armed forces and their families within the Mid-Eastern Province of Saudi Arabia.Antenatal care for KFAFH beneficiaries is provided by multiple primary care clinics within the hospital and the surrounding neighborhoods. As is the case in some other places, different screening methods are variably used in screening for GDM in these clinics. Both GCT and RBS are variably, but regularly, used. Universal GDM screening is adopted at all KFAFH clinics. For OGTT, the vast majority of physicians use the 3-hour 100-g OGTT recommended by the ADA, and veryWe utilized the hospital central laboratory database to identify the population of this study; this laboratory serves all the clinics, on- and off-campus. All OGTT tests that were performed between January 2001 and April 2002 were retrieved. Those tests associated with HbA1c measurements, performed concomitantly with OGTT or within two weeks of each other, were extracted. Corresponding patients were subsequently identified through an extensive review of medical records. To ensure homogeneity of data, we only included the 3-hour 100-g OGTT.For the purpose of this study, the diagnosis of GDM was retrospectively based on the results of the OGTT tests, according to cut-off values recommended by the ADA guidelines. These thOnce all corresponding patients were identified and through a review of their medical records, we included in our analysis all consecutive pregnant women who had paired OGTT/HbA1c measurements performed during the third trimester. Because this was a retrospective study, we could not evaluate the selection criteria used for screening of these patients nor the screening method (GCT or RBS) used. However, it was assumed that screening was performed universally, according to the general trend of the primary care providers, as alluded to earlier. Furthermore, this study was not designed to evaluate the clinical course, management or outcome of the GDM in the study population.The glucose measurements were performed on centrifuged venous blood, utilizing a standard commercial glucose oxidase method. The HbA1c assays were performed on EDTA whole blood, utilizing a Roche/Hitachi® analyzer . The assay method used in this analyzer is a turbidimetric inhibition immunoassay (TINIA). This assay method is not affected by either hemoglobinopathies or uremia. The imprThe study data were collected manually and then input into a computer database by using an SPSS software program, version 10.0.0, for Windows .Of a total of 319 paired sets of OGTT-HbA1c results retrieved from the laboratory database, a total of 145 eligible subjects were identified upon review of medical records. Of those patients, a total of 124 had a confirmed diagnosis of GDM according to the OGTT results. These patients were all Saudis with the exception of two Philippinos and one Yemeni. Their age (years), weight (kg) and gestational age (weeks) were 33 ± 6, 81 ± 16 and 32 ± 5 (Mean ± SD), respectively .n = 145) were as follows: RBS ; GCT . One patient had both tests performed. In the remaining patients (n = 36), we could not identify the screening method(s) employed upon an extensive review of laboratory databases and medical records.The screening methods that could be identified from reviewing the medical records of the study patients (n = 124), the HbA1c of the 21 patients with normal OGTT results was 6.4 ± 0.6% (P < 0.006).The local laboratory reference range for HbA1c was 4.8%–6.0% for the general population. The percentages of patients with diagnosed GDM who had HbA1c values above or equal to the upper reference cut-point values of 5.0%, 5.5%, 6.0%, 6.5% and 7.0% were100%, 98.4%, 87.1%, 62.9% and 39.5%, respectively . As compP < 0.006). Of these 21 patients, 16 (76.2%) had HbA1c ≥ 6.0%.This study has shown that the majority of women (108 of 124 or 87.1%) with confirmed diagnosis of GDM had elevated HbA1c . This suggests a reasonable sensitivity of HbA1c as a predictor of OGTT (the diagnostic gold standard), at an arbitrary HbA1c cut-point of 6%; due lack of controls, our data did not allow for a meaningful calculation of the test specificity. The study has also shown that the average HbA1c of the 21 patients with normal (negative) OGTT results (without GDM) was 6.4 ± 0.6% (n = 21) with normal (negative) OGTT results [Because of these (apparent) many false positives, which may suggest a lower specificity, we further analyzed the OGTT results of the aforementioned patients  has been recently addressed. Cianni  reported that pre reported labeled et al.[Of note, the aforementioned arbitrary upper-limit cut-off value (6.0%) which we used in the study is generally applicable in nonpregnant populations. However, a close cut-off value has been recently validated for pregnant women. Balaji et al. have recNevertheless and until a known cut-off value is universally adopted, we included results of sensitivities across a graded spectrum of five HbA1c cut-off values of 0.5% around the 6.0% cut-off, i.e., from 5.0% to 7.0%. These results were, expectedly dropping from 100% for the 5.0% cut-off value to 39.5% for the 7.0% value. These dropping sensitivity values are typical of diagnostic tests, losing sensitivity towards the higher-end values . Our datOur findings thus suggest a potential screening role for HbA1c, as a predictor of abnormal OGTT in this high risk population. In other words, if HbA1c was used as a screening measure in these patients, using the arbitrary cut-point of 6.0%, only 12.9% of the patients with confirmed GDM would be missed .Pioneered by Pollack and associates, previousThe most recently published studies addressing the screening potential of HbA1c in GDM were both reported by the same investigators , within the last six years.11 It is Our study has obvious limitations. First of all, the study was designed as a retrospective study, involving a special high-risk population. As such, the number of subjects with normal OGTT was too small to allow for calculation of the test specificity or negative predictive values. Since we are looking at HbA1c test solely as a screening test in this study, we believe that sensitivity is more relevant than specificity.Second, the study did not evaluate the clinical status or outcome of the subjects or how the screening methods were allocated as explained earlier. Using different screening methods added heterogeneity to our data. Finally, our study was not designed to evaluate the HbA1c level in relation to fetal outcomes, such as birth weight or neonatal complications. These clinical implications would be desirable in studies involving diagnostic tests.In conclusion, this study suggests that HbA1c may be a reasonably sensitive screening measure for prediction of GDM in high risk population. In other words, we suggest that HbA1c be used as an adjunct to GCT or RBS in screening for GDM in these populations. Further studies are warranted to evaluate the specificity and other diagnostic parameters of HbA1c before endorsing it as an alternative screening tool in populations.


To be eligible, patients had to present with residual disease after surgery. Planning was performed using the clinical target volume (CTV = GTV ∪ BTV) and planning target volume (PTV = CTV + 20 mm). First, the interrater reliability for BTV delineation was assessed among three observers. Second, the BTV and GTV were quantified and compared. Finally, the geometrical relationships between GTV and BTV were assessed.p = 0.9), CTVs (mean 57.8 ± 30.4 cm3) were significantly larger than BTVs  or GTVs . In 13 (68%) and 6 (32%) of 19 patients, FET uptake extended ≥ 10 and 20 mm from the margin of the gadolinium enhancement.Interrater agreement for BTV delineation was excellent (intraclass correlation coefficient 0.9). Although, BTVs and GTVs were not significantly different (Using FET, the interrater reliability had excellent agreement for BTV delineation. With FET PET-CT planning, the size and geometrical location of GTVs and BTVs differed in a majority of patients. Positron emission tomotherapy (PET) is used in neuro-oncology practice essentially for diagnosis,2, prognHigh-precision radiation therapy necessitates however precise anatomical and biological target delineation. [(18)F]fluoroethyltyrosine (FET) has been shown to have a high sensitivity >90%) and specificity (>80%) for glioma. In vitr0% and spDefining biological target volumes (BTVs) can result in substantial changes of target volumes for the planning of RT, as the size and location of FET is defined by metabolic activity rather than by the morphologic process of glioma growth, defined by magnetic resonance imaging (MRI),12. ThisThe purpose of this study was 1) to assess the interrater variability of high-grade glioma delineation using FET; 2) to quantify the BTVs and GTVs and to assess their volumetric and geometric relationships and 3) to assess the treatment characteristics after FET PET RT planning.de novo or recurrent high-grade glioma were eligible for this study. No previous RT to the brain or meninges interfering with the protocol treatment plan was however allowed for the latter patients. Postoperative treatment consisted of RT, using a linac with multileaf collimation , and concomitant temozolomide, followed by adjuvant temozolomide for all patients and T2- weighted sequence) were used mainly to assess the extend of resection and any residual disease was comprehensively included during the GTV delineation for any residual disease.Patient's diagnostic 1.5 Tesla MRI  studies  were transferred through the hospital picture archiving communication system (PACS) to the virtual simulation workstation . All brain CT images were interpreted by an experienced diagnostic radiologist. The PET, CT, and fused PET/CT images were displayed for review in axial, coronal, and sagital planes. All studies were interpreted and reviewed with knowledge of the patient's clinical history and results of previous imaging studies. The biopsied tumor, or residual tumor, defined by FET uptake was delineated manually. Maximum standardized uptake values (SUVmax) were calculated for ROIs of focal hyperactivity by dividing the observed activity per gram in attenuation corrected PET with the injected activity per gram body weight - [BTVDCW ∩ BTVHV ∩ BTVTZ]. Observer's BTVs, OMMONCBTVs and IFFDBTVs were transferred to the AcQSim® workstation using the PACS for planning purposes. A BTV-interrater agreement was assessed by intraclass correlation coefficient (ICC) computations - [GTV ∩ BTV]) was computed. The Boolean operator in the Eclipse® TPS was used for volume measurements and volume mismatch analysis. In case of BTV/GTV mismatch, the differential margins of these two volumes were measured on axial slices.The GTV data was also transferred from the AcQSimFor treatment planning, the MD Anderson Cancer Center target policy was used. Plannin3, respectively. Excluding this latter patient, the median percentage-difference between the study and matched patients was 0.7% .As to determine the impact of FET PET-guided RT planning, the treatment characteristics of the study patients were retrospectively assessed. The treatment characteristics of 19 other matched high-grade glioma patients  were also analyzed. The difference of all study and matched patient's GTV were less than 10%, except for a patient with a brainstem glioblastoma. For this case and his matched counterpart, GTVs were 4.5 and 2.2 cmp value of less than 0.05 was considered to indicate statistical significance.We performed all analyses using the Statistical Package for Social Sciences . For descriptive analyses of patients' characteristics and volumes sizes we used percents and mean score. The GTV, BTV and CTV delineation methods were compared using the Wilcoxon signed-rank test as numerical data were not normally distributed. The field size comparisons of the FET PET-guided- and non-FET PET-guided RT were performed using the Man Whitney U test. Statistical analyses used to test the interrater reliability of the biological tumor volume delineation by the three observers were the intraclass correlation coefficient and analysis of variance with the expectation to uphold the null hypothesis. A two-smax at 0 – 10, 10 – 20, 20 – 30 minutes were 3.05 , 3.64  and 3.77 , respectively. Fig. 3, respectively. The interrater agreement was excellent (ICC = 0.9) and volumetric difference between observer's BTV delineation did not reach statistical significance (p = 0.99). The mean OMMONCBTV was 32.0 ± 20.1 cm3. The IFFDBTV ranged from 0.3 to 19.0 cm3 .Abnormal FET uptake was observed in all patients. Median SUVp = 0.9) than their morphologic counterpart: mean BTV and GTV were 35.8 ± 21.7 and 38.4 ± 25.7 cm3, respectively  or the BTV (p < 0.01). For the whole group, the mean CTV was 57.8 ± 30.4 cm3and the mean OMMONCCTV was 22.8 ± 15.1 cm3 /(CTV) was 37.3% and ranged from 6.8% to 67.5%, indicating a mismatch in a substantial number of patients. FET uptake was detected up to 34.8 mm beyond gadolinium enhancement  in 1 patient. The mean BTV located outside the GTV was 18.3 ± 12.4 cm3 and ranged from 3.2 to 45.5. Thus, the percentage of BTV not included in the GTV ranged from 3.9% to 155.2% , bearing in mind that occasionally the BTV was larger than the GTV. In 13 (68%) and 6 (32%) of 19 patients, FET uptake extended = 10 and 20 mm from the margin of the gadolinium enhancement. Likewise, gadolinium enhancement was detected up to 35.9 mm beyond FET uptake  in 1 patient. The mean GTV located outside the BTV was 15.0 ± 22.3 cm3and ranged from 0.0 to 93.8. In 12 (63%) and 4 (21%) of 19 patients, gadolinium enhancement extended = 10 and 20 mm from the margin of the FET uptake. The target volumes are presented in Fig Unsurprisingly, the CTV, with which the patients were planned, were significantly larger than the GTV  and axial treatment fields  of FET PET-guided and non-FET PET-guided RT were not significantly different.The mean number of treatment fields for the FET PET-guided- and non-FET PET-guided RT were 2.5  and 2.6 , respectively. The size of the lateral , although the tracer's kinetics were indeed differentfluoroethyltyrosine; FDG: 18F-fluorodeoxyglucose; BTV: biological target volume; MRI: magnetic resonance imaging; GTV: gross tumour volume; PTV: planning target volume. CTV: Clinical tumor volume; The authors declare that they have no competing interests.DCW was responsible for the primary concept and the design of the study; DCW, TZ, NC and HJV performed the data capture and analysis. DCW drafted the manuscript; GH performed the statistical analysis; DCW and TZ reviewed patient data; FB, HZ, RO and RM revised the manuscript.