IMPACT OF PROPHYLACTIC USE OF COLONY STIMULATING FACTORS ON THE PATTERN OF NEUTROPENIA AND INFECTIONS IN MODERATELY INTENSIVE CHEMOTHERAPY

In this study, colony stimulating factors (CSF) were used to prevent neutropenia during moderately intensive chemotherapy in 26 episodes of chemotherapy (12 of acute lymphoblastic leukaemia (ALL) and 14 patients with other malignancies). CSF was administered in doses of 5 µg/kg of body weight within 24 hours of completion of chemotherapy for 7 days in 6 patients and for 10 days in others. Twenty six age and sex matched patients of ALL were included as controls. In the CSF group, incidence of severe neutropenia (grades 3 and 4) reduced significantly by 42.3 per cent though overall incidence of neutropenia did not differ much. Mean duration of neutropenia reduced by 4 days. Nadir total leucocyte count and absolute neutrophil count were significantly higher. There was no difference in the incidence of anaemia, thrombocytopenia and requirement of blood transfusions. Overall infections were less and incidence of severe infections reduced by 42.3 per cent. The duration of infection and of fever was shortened. Requirement of antibiotics was also reduced. All patients in CSF group recovered from infection, while 1 patient died in the control group. Mean duration of delay in chemotherapy was reduced from 10 days in control group to 3 days in CSF group. CSF administration resulted in an escalation of the cost by 112.24 per cent. However shortened duration of antibiotics, hospitalisation, reduced laboratory expenses compensated it by 66.94 per cent Our study indicates that the prophylactic use of CSF is beneficial and cost effective in moderately intensive chemotherapy with a high incidence of febrile neutropenia. Administration for 10 days appears to be more beneficial than 7 days.KEYWORDS: Chemotherapy, Colony Stimulating Factors, Cost-Benefit Analysis, Neutropenia, Prophylaxis     

Peritoneal interleukin-10 increases with decrease in activated CD4+ T lymphocytes in women with endometriosis

This study was performed to determine whether peritoneal T cells are suppressed in the CD4+ or CD8+ T cell subpopulation and whether they are Th1 or Th2 predominant in women with endometriosis. Immune cells in the peritoneal fluid (PF) were obtained from women undergoing laparoscopy for endometriosis or tubal ligation. Three-colour flow cytometry was utilized for immunophenotyping of peritoneal fluid mononuclear cells (PFMC). Concentrations of interleukin (IL)-4, IL-5 and interferon-gamma (IFN-gamma) produced by PFMC with and without mitogen stimulation and concentrations of IL-10 and IL-12 were measured in PF. The peritoneal T lymphocytes were predominantly of the Th1 type that produced much more IFN-gamma but less IL-4 or IL-5 in women with or without endometriosis. The decrease in peritoneal lymphocytes was significant in the HLA-DR+ CD4+ CD3+ subpopulation and the concentrations of peritoneal IL-10 and IL-12 were significantly elevated in women with early stage endometriosis. There was impaired IL- 5 production by PFMC after phytohaemagglutinin stimulation in women with advanced stage endometriosis. We concluded that the activated peritoneal CD4+ Th1 cells from the women with endometriosis were decreased in number. The suppression of these T cells may be due to the elevation of IL-10 and IL-12 in the peritoneal fluid.      

Paired human chorionic gonadotrophin determinations for the prediction of pregnancy outcome in assisted reproduction

The aim of this study was to determine the prognostic value of single and paired measurements of serum concentrations of human chorionic gonadotrophin (HCG) for successful pregnancy following in-vitro fertilization (IVF) and tubal embryo transfer (TET). We analysed serum HCG concentrations 15 and 22 days after IVF or TET in 198 conception cycles. Cut-off values of serum HCG were determined by a receiver operating characteristic (ROC) curve. On the basis of single HCG samples on day 15 (HCG15) after transfer, using a cut-off value of HCG15 = 150 mIU/ml, the sensitivity was 71% and the specificity was 77%. The positive predictive value (HCG15 > or = 150 mIU/ml indicating a normal pregnancy) was 89%, while the negative predictive rate (HCG15 < 150 mIU/ml indicating an abnormal pregnancy) was 51%. Patients with HCG15 < 150 mIU/ml but HCG22/HCG15 ratio > or = 15, still had a 90% chance of normal pregnancy. However, in patients with HCG15 < 150 mIU/ml and an HCG22/HCG15 ratio < 15, there was an 84% chance of an abnormal pregnancy. We conclude that a single HCG15 determination combined with the ratio of HCG22 to HCG15 has a higher diagnostic accuracy for prediction of pregnancy outcome than either analysis alone.      

Total antioxidant status and nitric oxide do not increase in peritoneal fluids from women with endometriosis

To explore the role of nitric oxide (NO) and oxidative stress in the pathogenesis of adhesion formation and in endometriosis-associated infertility, we examined the peritoneal total antioxidant status (TAS) and the concentrations of products of NO metabolism in women with endometriosis (early stage, n = 12; advanced stage, n = 12) and in fertile women without endometriosis (n = 10). Peritoneal CA 125 and oestrogen and progesterone concentrations were also measured to examine their contributions to TAS and the production of NO. We failed to demonstrate any significant difference in TAS and in the products of NO metabolism in peritoneal fluids among women with early and advanced stages of endometriosis compared with fertile women without endometriosis during the early follicular phase. TAS and the concentration of the products of NO metabolism were not related to concentrations of CA 125, oestrogen or progesterone. The concentration of CA 125 in serum, but not in peritoneal fluid, was positively correlated with the severity of endometriosis. The volume of peritoneal fluid and the progesterone concentration were significantly increased in the group with advanced endometriosis. TAS and the concentration of the products of NO metabolism did not increase in peritoneal fluids from women with endometriosis during the early follicular phase. Their role in the pathophysiology of endometriosis needs to be explored further.      

Survey of factor V leiden and prothrombin gene mutations in systemic lupus erythematosus

The two most common hereditary risk factors for thrombosis are factor V Leiden mutation and a prothrombin gene mutation. There is indeed a thrombotic tendency in patients with systemic lupus erythematosis (SLE) and it is not always associated with antiphospholipid antibodies. We aimed to determine the relationship between both factor V Leiden and prothrombin gene mutations and SLE. Using polymerase chain reaction (PCR) the factor V Leiden and prothrombin gene mutations were evaluated in 55 patients (20 children and 35 adults) with SLE. Although seven patients were found to have factor V Leiden mutation in the heterozygous state, two had the heterozygous G→A (20210) prothrombin gene mutation. Although one had these two mutations concurrently, these two patients did not have thrombosis. The factor V Leiden mutation frequency (12.7%) was higher than that of our general population (7.1%). On the other hand, seven of the patients with SLE had a thrombotic event. Although of these seven, four (57%) had factor V Leiden mutation, three (43%) had no mutation. Of 48 patients with no thrombotic history, only three had the factor V mutation (6.25%). The prevalence of the factor V Leiden mutation in SLE patients with and without thrombosis was significantly different by Fisher’s exact test (p<0.05). The risk of venous thrombosis in patients with factor V Leiden increased threefold compared to that in those without factor V Leiden mutation (odds ratio 20.1; CI 2.99–133.6). Although factor V Leiden mutation seems to play a role in the development of venous thrombosis in SLE, the development of thrombosis in SLE is multifactorial. Received: 1 August 2000 / Accepted: 9 March 2001     

心力衰竭患者血清CA125、CA19-9水平变化及意义

目的探讨慢性心衰(CHF)患者血清CA125、CA19-9水平变化及意义。方法(1)研究对象与分组:心衰组(CHF),按AHA指南标准随机人选17例慢性心衰患者,心功能Ⅱ-Ⅳ级(NY-HA),年龄36-86(51.7±13.2)岁。其中风湿性心脏病4例,高血压6例,冠心病5例,贫血性心脏病1例,其他1例;在这17例病例中合并心包积液2例、胸腔积液1例、心房纤颤3例,左心房及静脉血栓1例;非心衰组(NHF),冠心病(非心衰者)、高血压Ⅰ期患者13例,年龄21-77岁,健康对照组(Control),健康成年人15例,年龄25-73岁;(2)CA125、CA19-9测定:抽取清晨空腹静脉血5ml,化学发光免疫法测定血清CA125、CA19-9水平。同时,检测肿瘤三项(CEA、AFP、SF)、胸片、头颅CT以及腹部、盆腔超声,排外潜在的肿瘤;(3)统计学分析:数据采用均数±标准差(x±s)表示,t检验,P<0.05有统计学意义。结果与非心衰组和健康对照组比较,心衰组血清CA125显著升高,且与心衰严重程度(Ⅱ、Ⅲ、Ⅳ级)相关(分别P<0.01,P<0.001,P<0.001);非心衰组与健康对照组比较,无显著差别(P>0.05)。然而,各组间CA19-9水平无显著变化(P>0.05)。同时,发现合并心包、胸腔积液,尤其慢性房颤者,CA125显著升高。结论CA125是诊断和评价慢性心衰的一个良好指标,且与心衰程度相关,而CA19-9与心衰无明显关系。     

The prevalence of extraintestinal manifestations and HLA association in patients with inflammatory bowel disease

To determine the prevalence, clinical and radiological characteristics of spondyloarthropathy (SpA) in patients with inflammatory bowel disease (IBD), to assess the association between HLA B27 and B51 and the extraintestinal symptoms and to evaluate whether IBD is associated with Behçet’s disease (BD). One hundred and sixty-two consecutive adult patients with established diagnosis of IBD as either Crohn’s disease (CD) or ulcerative colitis (UC) were evaluated. All the patients including those previously diagnosed with or without SpA had a complete rheumatologic examination and they were evaluated according to the European Spondyloarthropathy Study Group (ESSG) criteria for SpA and The International Study Group for Behçet’s disease criteria for BD. The demographic and clinical data were recorded on a standardized form. The radiographies were obtained in all the patients and computed tomography (CT) was performed in the patients with suspected pelvic radiographies and/or low back pain in the physical examination. Radiological evaluation was made according to the Modified New York criteria. HLA B27, B51 and anti-neutrophile cytoplasmic antigen (ANCA) were searched in all the patients. Of the 162 patients with IBD (mean age 41.48±11.63 years, male 60, female 102), 78 were CD and 84 were UC. The mean of the IBD duration was 54.92±50.32 months and SpA duration was 20.63±34.37 months. The prevalence of SpA and AS in IBD was 45.7 and 9.9%, respectively. Frequencies of SpA and AS, the difference between UC and CD were not significant. Spondylitis, enthesitis, peripheral arthritis, oral ulcer and uveitis were not different between UC and CD, but erythema nodosum was found significantly more common in the CD patients compared with UC patients (P=0.005). The duration of IBD and SpA was similar in both groups. As the IBD duration increased, the prevalence of SpA development decreased (rr=0.991, P=0.009). Of the IBD patients, 13.6% were asymptomatic for musculoskeletal manifestations of SpA and their sacroiliac radiographies and CTs showed grade 2 sacroiliitis. HLA B27, B51 and ANCA positivities were not different between the patients with UC and CD. HLA B27 was significantly more common in the patients with sacroiliitis, spondylitis, enthesitis, peripheral arthritis, erythema nodosum, uveitis (P<0.001) and oral ulcer (P=0.025). BD was diagnosed in none of the patients. ANCA positivity was found to be related with the presence of erythema nodosum and uveitis (P=0.001 and P=0.005). The prevalence of SpA and AS is higher in the prospectively evaluated patients with radiological studies than those in the previously published studies. There is a high prevalence of asymptomatic sacroiliitis in IBD. An early diagnosis of inflammatory arthritis in IBD patients may prevent a disability due to SpA and AS.     

Primary drug resistance and transmission analysis of HIV-1 in acute and recent drug-naïve seroconverters in Singapore

Objectives

The aim of the study was to elucidate primary drug resistance and transmission of HIV‐1 in acute and recent drug‐naïve seroconverters in Singapore.

Methods

Acute and recent HIV‐1 seroconverters were enrolled in the study. The HIV‐1 polymerase (pol) gene was sequenced and used for genotypic drug resistance analysis and phylogenetic analysis. HIV‐1 transmission clusters were inferred from phylogenetic clustering analysis.

Results

Of the 60 subjects analysed, 95% were men, and 73.3% were men who have sex with men (MSM). Six HIV‐1 subtypes were identified, including CRF01_AE (46.7%), subtypes B (30%), B′ (15%) and G (1.7%), CRF33_01B (1.7%) and CRF34_01B (5%). Primary genotypic resistance was detected in only one (1.7%) subtype B variant. Thirty‐one patients (51.7%) were phylogenetically clustered, of whom 90% reported having local risk exposure, compared with 59% of the patients who were not phylogenetically clustered [odds ratio (OR) 6.35, 95% confidence interval (CI) 1.65–23.95]. MSM (OR 5.63, 95% CI 1.17–27.15), high viral load (OR 4.28, 95% CI 1.37–13.36) and young age (OR 0.92, 95% CI 0.85–0.99) were independently associated with clustered individuals.

Conclusions

In Singapore, HIV‐1 primary resistance is insignificant; individuals with seroconversion account for about half of onward transmission among recently infected seroconverters. MSM, high viral load and young age are factors that facilitate transmission. Early detection of these individuals is of paramount importance for the prevention of HIV‐1 transmission.